Clinical Trial Results:
A Randomised, open labelled study in antiTNFa inadequate responders to investigate the mechanisms for Response  Resistance to Rituximab versus Tocilizumab in RA (R4RA)
Summary


EudraCT number 
201200253528 
Trial protocol 
GB PT BE IT ES NL 
Global end of trial date 
11 Jul 2019

Results information


Results version number 
v1(current) 
This version publication date 
05 Jul 2020

First version publication date 
05 Jul 2020

Other versions 

Summary report(s) 
SAEs occuring after treatment phase of study 
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information


Trial identification


Sponsor protocol code 
R4RA


Additional study identifiers


ISRCTN number 
ISRCTN97443826  
US NCT number 
  
WHO universal trial number (UTN) 
  
Sponsors


Sponsor organisation name 
Queen Mary University of London


Sponsor organisation address 
Joint Research Management Office QM Innovation Building, 5 Walden Street, London, United Kingdom, E1 2EF


Public contact 
Professor Costantino Pitzalis, Centre for Experimental Medicine and Rheumatology, Queen Mary University of London, emrclinicaltrials@qmul.ac.uk


Scientific contact 
Professor Costantino Pitzalis, Centre for Experimental Medicine and Rheumatology, Queen Mary University of London, c.pitzalis@qmul.ac.uk


Paediatric regulatory details


Is trial part of an agreed paediatric investigation plan (PIP) 
No


Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? 
No


Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? 
No


Results analysis stage


Analysis stage 
Final


Date of interim/final analysis 
05 Feb 2019


Is this the analysis of the primary completion data? 
Yes


Primary completion date 
31 Jan 2019


Global end of trial reached? 
Yes


Global end of trial date 
11 Jul 2019


Was the trial ended prematurely? 
No


General information about the trial


Main objective of the trial 
The main aim of this project is to test the hypothesis that the presence or absence of specific synovial cellular and molecular signatures(B cells and B cellassociated signatures), assessed following a synovial tissue biopsy, will enrich for response / nonresponse to the B cell depleting antiCD20 monoclonal antibody (mAb) Rituximab.
The primary aim of this project is to show that in patients failing antiTNF therapy, with a B cell poor synovial pathotype, Rituximab is inferior to Tocilizumab therapy.


Protection of trial subjects 
Both IMPs being used in this trial are approved for use in this patient population. Infusions of Rituximab may be associated with infusion reactions of varying severity in up to 15% of patients. Most are mild and managed by slowing the rate of the Rituximab infusion. Occasionally, more severe reactions necessitate stopping the infusion and rarely, anaphylaxis has been reported. Patients will be given corticosteroids (methylprednisolone 100mg intravenous), antihistamines (chlorphenamine 10mg intravenous) and paracetamol (1000mg orally) before the infusion to minimise the risk of reactions. The risk of infection will be discussed with the patient prior to enrolment in the study however patients would be at no greater risk than routine care within the NHS.
Infusion reactions with Tocilizumab are rare. Occasionally patients may experience chills or fevers but these are selflimiting or rarely requiring paracetamol. The risk of infection will be discussed with the patient prior to enrolment in the study however patients would be at no greater risk than routine care within the NHS.
Ultrasoundguided synovial biopsy is a quick, safe and well tolerated procedure; patients who consent to the study and therefore synovial biopsy will have a longer appointment in hospital and may have discomfort from the local anaesthetic and biopsy procedure however audit data of this procedure confirms that it is well tolerated and patients are agreeable to multiple biopsies.
The risks of venepuncture may include fainting, pain and/or bruising at the site of the needle puncture. Every possible effort will be taken to minimise the potential of these risks occurring.


Background therapy 
Only entry into the trial patients should be receiving a stable dose Methotrexate for at least 4 weeks prior to biopsy visit.  
Evidence for comparator 
N/A  
Actual start date of recruitment 
28 Feb 2013


Long term followup planned 
No


Independent data monitoring committee (IDMC) involvement? 
Yes


Population of trial subjects


Number of subjects enrolled per country 

Country: Number of subjects enrolled 
Portugal: 9


Country: Number of subjects enrolled 
Spain: 6


Country: Number of subjects enrolled 
United Kingdom: 109


Country: Number of subjects enrolled 
Belgium: 26


Country: Number of subjects enrolled 
Italy: 14


Worldwide total number of subjects 
164


EEA total number of subjects 
164


Number of subjects enrolled per age group 

In utero 
0


Preterm newborn  gestational age < 37 wk 
0


Newborns (027 days) 
0


Infants and toddlers (28 days23 months) 
0


Children (211 years) 
0


Adolescents (1217 years) 
0


Adults (1864 years) 
120


From 65 to 84 years 
44


85 years and over 
0



Recruitment


Recruitment details 
Patients were recruited from rheumatology clinics across 19 sites in the United Kingdom, Italy, Belgium, Portugal and Spain. Recruitment began in February 2013 and ended in November 2017.  
Preassignment


Screening details 
212 patients were approached to join the study, and 190 of these went on to consent to participation in the trial. 26 of these did not continue to randomization, 13 did not meet the inclusion criteria following the screening visit, 6 declined further participation (3 due to the biopsy), and 7 for other reasons not recorded.  
Period 1


Period 1 title 
Baseline


Is this the baseline period? 
Yes  
Allocation method 
Randomised  controlled


Blinding used 
Not blinded  
Arms


Are arms mutually exclusive 
Yes


Arm title

Rituximab  
Arm description 
Patients randomized to rituximab who received at least one dose of IMP  
Arm type 
Active drug  
Investigational medicinal product name 
Rituximab


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Concentrate for solution for infusion


Routes of administration 
Intravenous use


Dosage and administration details 
Rituximab is available as 50ml singleuse vials containing 500mg Rituximab for infusion (10mg/ml). Patients randomised to Rituximab will have an infusion cycle at baseline consisting of two infusions given 2 weeks apart (Day 0 and Day 15). A patient initially randomised to Rituximab, deemed a responder at 16 weeks (CDAI ≥50% improvement from baseline assessment) who continues to have active disease (CDAI ≥10.1) or flares (CDAI ≥10.1) will be retreated at 24 weeks, as per the SmPC.
Rituximab was prescribed according as per license and thus was sourced from local clinical supplies at each trial site.


Arm title

Tocilizumab  
Arm description 
Patients randomized to tocilizumab who received at least one dose of IMP  
Arm type 
Active drug  
Investigational medicinal product name 
Tocilizumab


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Concentrate for solution for infusion


Routes of administration 
Intravenous use


Dosage and administration details 
Tocilizumab is available in 20mg/ml vials in a concentrate for intravenous infusion. Tocilizumab was prescribed according as per license and thus was sourced from local clinical supplies at each trial site. Infusions were given every 4 weeks starting at baseline with the last infusion given at 44 weeks.




Notes [1]  The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: 212 patients were approached to join the study, and 190 of these went on to consent to participation in the trial. 26 of these did not continue to randomization, 13 did not meet the inclusion criteria following the screening visit, 6 declined further participation (3 due to the biopsy), and 7 for other reasons not recorded. 

Period 2


Period 2 title 
Baseline to Week 16


Is this the baseline period? 
No  
Allocation method 
Randomised  controlled


Blinding used 
Not blinded  
Arms


Are arms mutually exclusive 
Yes


Arm title

Rituximab  
Arm description 
  
Arm type 
Active drug  
Investigational medicinal product name 
Rituximab


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Concentrate for solution for infusion


Routes of administration 
Intravenous use


Dosage and administration details 
Rituximab is available as 50ml singleuse vials containing 500mg Rituximab for infusion (10mg/ml). Patients randomised to Rituximab will have an infusion cycle at baseline consisting of two infusions given 2 weeks apart (Day 0 and Day 15). A patient initially randomised to Rituximab, deemed a responder at 16 weeks (CDAI ≥50% improvement from baseline assessment) who continues to have active disease (CDAI ≥10.1) or flares (CDAI ≥10.1) will be retreated at 24 weeks, as per the SmPC.
Rituximab was prescribed according as per license and thus was sourced from local clinical supplies at each trial site.


Arm title

Tocilizumab  
Arm description 
  
Arm type 
Active drug  
Investigational medicinal product name 
Tocilizumab


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Concentrate for solution for infusion


Routes of administration 
Intravenous use


Dosage and administration details 
Tocilizumab is available in 20mg/ml vials in a concentrate for intravenous infusion. Tocilizumab was prescribed according as per license and thus was sourced from local clinical supplies at each trial site. Infusions were given every 4 weeks starting at baseline with the last infusion given at 44 weeks.




Period 3


Period 3 title 
Week 16 to Week 48


Is this the baseline period? 
No  
Allocation method 
Randomised  controlled


Blinding used 
Not blinded  
Arms


Are arms mutually exclusive 
Yes


Arm title

Rituximab  
Arm description 
Patients who were randomized to rituximab and did not switch treatment for the duration of the trial.  
Arm type 
Active drug  
Investigational medicinal product name 
Rituximab


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Concentrate for solution for infusion


Routes of administration 
Intravenous use


Dosage and administration details 
Rituximab is available as 50ml singleuse vials containing 500mg Rituximab for infusion (10mg/ml). Patients randomised to Rituximab will have an infusion cycle at baseline consisting of two infusions given 2 weeks apart (Day 0 and Day 15). A patient initially randomised to Rituximab, deemed a responder at 16 weeks (CDAI ≥50% improvement from baseline assessment) who continues to have active disease (CDAI ≥10.1) or flares (CDAI ≥10.1) will be retreated at 24 weeks, as per the SmPC.
Rituximab was prescribed according as per license and thus was sourced from local clinical supplies at each trial site.


Arm title

Tocilizumab  
Arm description 
Patients who were randomized to tocilizumab and did not switch treatment for the duration of the trial.  
Arm type 
Active drug  
Investigational medicinal product name 
Tocilizumab


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Concentrate for solution for infusion


Routes of administration 
Intravenous use


Dosage and administration details 
Tocilizumab is available in 20mg/ml vials in a concentrate for intravenous infusion. Tocilizumab was prescribed according as per license and thus was sourced from local clinical supplies at each trial site. Infusions were given every 4 weeks starting at baseline with the last infusion given at 44 weeks.


Arm title

Rituximab+Tocilizumab  
Arm description 
Patients who were randomized to rituximab but switched to tocilizumab at week 16 or later.  
Arm type 
Active drug  
Investigational medicinal product name 
Rituximab


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Concentrate for solution for infusion


Routes of administration 
Intravenous use


Dosage and administration details 
Rituximab is available as 50ml singleuse vials containing 500mg Rituximab for infusion (10mg/ml). Patients randomised to Rituximab will have an infusion cycle at baseline consisting of two infusions given 2 weeks apart (Day 0 and Day 15). A patient initially randomised to Rituximab, deemed a responder at 16 weeks (CDAI ≥50% improvement from baseline assessment) who continues to have active disease (CDAI ≥10.1) or flares (CDAI ≥10.1) will be retreated at 24 weeks, as per the SmPC.
Rituximab was prescribed according as per license and thus was sourced from local clinical supplies at each trial site.


Investigational medicinal product name 
Tocilizumab


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Concentrate for solution for infusion


Routes of administration 
Intravenous use


Dosage and administration details 
Tocilizumab is available in 20mg/ml vials in a concentrate for intravenous infusion. Tocilizumab was prescribed according as per license and thus was sourced from local clinical supplies at each trial site. Infusions were given every 4 weeks starting at baseline with the last infusion given at 44 weeks.


Arm title

Tocilizumab+Rituximab  
Arm description 
Patients who were randomized to tocilizumab and were switched to rituximab at week 16 or later  
Arm type 
Active drug  
Investigational medicinal product name 
Tocilizumab


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Concentrate for solution for infusion


Routes of administration 
Intravenous use


Dosage and administration details 
Tocilizumab is available in 20mg/ml vials in a concentrate for intravenous infusion. Tocilizumab was prescribed according as per license and thus was sourced from local clinical supplies at each trial site. Infusions were given every 4 weeks starting at baseline with the last infusion given at 44 weeks.


Investigational medicinal product name 
Rituximab


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Concentrate for solution for infusion


Routes of administration 
Intravenous use


Dosage and administration details 
Rituximab is available as 50ml singleuse vials containing 500mg Rituximab for infusion (10mg/ml). Patients randomised to Rituximab will have an infusion cycle at baseline consisting of two infusions given 2 weeks apart (Day 0 and Day 15). A patient initially randomised to Rituximab, deemed a responder at 16 weeks (CDAI ≥50% improvement from baseline assessment) who continues to have active disease (CDAI ≥10.1) or flares (CDAI ≥10.1) will be retreated at 24 weeks, as per the SmPC.
Rituximab was prescribed according as per license and thus was sourced from local clinical supplies at each trial site.





Baseline characteristics reporting groups


Reporting group title 
Rituximab


Reporting group description 
Patients randomized to rituximab who received at least one dose of IMP  
Reporting group title 
Tocilizumab


Reporting group description 
Patients randomized to tocilizumab who received at least one dose of IMP  



End points reporting groups


Reporting group title 
Rituximab


Reporting group description 
Patients randomized to rituximab who received at least one dose of IMP  
Reporting group title 
Tocilizumab


Reporting group description 
Patients randomized to tocilizumab who received at least one dose of IMP  
Reporting group title 
Rituximab


Reporting group description 
  
Reporting group title 
Tocilizumab


Reporting group description 
  
Reporting group title 
Rituximab


Reporting group description 
Patients who were randomized to rituximab and did not switch treatment for the duration of the trial.  
Reporting group title 
Tocilizumab


Reporting group description 
Patients who were randomized to tocilizumab and did not switch treatment for the duration of the trial.  
Reporting group title 
Rituximab+Tocilizumab


Reporting group description 
Patients who were randomized to rituximab but switched to tocilizumab at week 16 or later.  
Reporting group title 
Tocilizumab+Rituximab


Reporting group description 
Patients who were randomized to tocilizumab and were switched to rituximab at week 16 or later  
Subject analysis set title 
SAF


Subject analysis set type 
Safety analysis  
Subject analysis set description 
Safety analysis set


Subject analysis set title 
ITT week 16  B cell poor Rituximab


Subject analysis set type 
Intentiontotreat  
Subject analysis set description 
Subgroup of patients classified as B cell poor by histology classification and analysed as ITT at week 16


Subject analysis set title 
ITT week 16  B cell poor Tocilizumab


Subject analysis set type 
Intentiontotreat  
Subject analysis set description 
Subgroup of patients classified as B cell poor by histology classification and analysed as ITT at week 16


Subject analysis set title 
ITT week 16  B cell rich Rituximab


Subject analysis set type 
Intentiontotreat  
Subject analysis set description 
Subgroup of patients classified as B cell rich by histology classification and analysed as ITT at week 16


Subject analysis set title 
ITT week 16  B cell rich Tocilizumab


Subject analysis set type 
Intentiontotreat  
Subject analysis set description 
Subgroup of patients classified as B cell rich by histology classification and analysed as ITT at week 16


Subject analysis set title 
ITT week 16  B cell poor (RNA_seq) Rituximab


Subject analysis set type 
Intentiontotreat  
Subject analysis set description 
Subgroup of patients classified as B cell poor by RNAseq classification and analysed as ITT at week 16


Subject analysis set title 
ITT week 16  B cell poor (RNA_seq) Tocilizumab


Subject analysis set type 
Intentiontotreat  
Subject analysis set description 
Subgroup of patients classified as B cell poor by RNAsequencing classification and analysed as ITT at week 16


Subject analysis set title 
ITT week 16  B cell rich (RNA_seq) Rituximab


Subject analysis set type 
Intentiontotreat  
Subject analysis set description 
Subgroup of patients classified as B cell rich by RNAsequencing classification and analysed as ITT at week 16


Subject analysis set title 
ITT week 16  B cell rich (RNA_seq) Tocilizumab


Subject analysis set type 
Intentiontotreat  
Subject analysis set description 
Subgroup of patients classified as B cell rich by RNAsequencing classification and analysed as ITT at week 16


Subject analysis set title 
PP week 16  B cell poor Rituximab


Subject analysis set type 
Per protocol  
Subject analysis set description 
Subgroup of patients classified as B cell poor by histology classification and analysed as PP at week 16


Subject analysis set title 
PP week 16  B cell poor Tocilizumab


Subject analysis set type 
Per protocol  
Subject analysis set description 
Subgroup of patients classified as B cell poor by histology classification and analysed as PP at week 16


Subject analysis set title 
PP week 16  B cell rich Rituximab


Subject analysis set type 
Per protocol  
Subject analysis set description 
Subgroup of patients classified as B cell rich by histology classification and analysed as PP at week 16


Subject analysis set title 
PP week 16  B cell rich Tocilizumab


Subject analysis set type 
Per protocol  
Subject analysis set description 
Subgroup of patients classified as B cell rich by histology classification and analysed as PP at week 16


Subject analysis set title 
PP week 16  B cell poor (RNA_seq) Rituximab


Subject analysis set type 
Per protocol  
Subject analysis set description 
Subgroup of patients classified as B cell poor by RNA sequencing classification and analysed as PP at week 16


Subject analysis set title 
PP week 16  B cell poor (RNA_seq) Tocilizumab


Subject analysis set type 
Per protocol  
Subject analysis set description 
Subgroup of patients classified as B cell poor by RNAsequencing classification and analysed as PP at week 16


Subject analysis set title 
PP week 16  B cell rich (RNA_seq) RItuximab


Subject analysis set type 
Per protocol  
Subject analysis set description 
Subgroup of patients classified as B cell rich by RNAsequencing classification and analysed as PP at week 16


Subject analysis set title 
PP week 16  B cell rich (RNA_seq) Tocilizumab


Subject analysis set type 
Per protocol  
Subject analysis set description 
Subgroup of patients classified as B cell rich by RNAsequencing classification and analysed as PP at week 16


Subject analysis set title 
week 24  B cell poor Rituximab


Subject analysis set type 
Per protocol  
Subject analysis set description 
Subgroup of patients classified as B cell poor by histology classification and analysed as PP at week 24


Subject analysis set title 
week 24  B cell poor Tocilizumab


Subject analysis set type 
Per protocol  
Subject analysis set description 
Subgroup of patients classified as B cell poor by histology classification and analysed as PP at week 24


Subject analysis set title 
week 24  B cell rich Rituximab


Subject analysis set type 
Per protocol  
Subject analysis set description 
Subgroup of patients classified as B cell rich by histology classification and analysed as PP at week 24


Subject analysis set title 
week 24  B cell rich Tocilizumab


Subject analysis set type 
Per protocol  
Subject analysis set description 
Subgroup of patients classified as B cell rich by histology classification and analysed as PP at week 24


Subject analysis set title 
week 36  B cell poor Rituximab


Subject analysis set type 
Per protocol  
Subject analysis set description 
Subgroup of patients classified as B cell poor by histology classification and analysed as PP at week 36


Subject analysis set title 
week 36  B cell poor Tocilizumab


Subject analysis set type 
Per protocol  
Subject analysis set description 
Subgroup of patients classified as B cell poor by histology classification and analysed as PP at week 36


Subject analysis set title 
week 36  B cell rich Rituximab


Subject analysis set type 
Per protocol  
Subject analysis set description 
Subgroup of patients classified as B cell rich by histology classification and analysed as PP at week 36


Subject analysis set title 
week 36  B cell rich Tocilizumab


Subject analysis set type 
Per protocol  
Subject analysis set description 
Subgroup of patients classified as B cell rich by histology classification and analysed as PP at week 36


Subject analysis set title 
week 48  B cell poor Rituximab


Subject analysis set type 
Per protocol  
Subject analysis set description 
Subgroup of patients classified as B cell poor by histology classification and analysed as PP at week 48


Subject analysis set title 
week 48  B cell poor Tocilizumab


Subject analysis set type 
Per protocol  
Subject analysis set description 
Subgroup of patients classified as B cell poor by histology classification and analysed as PP at week 48


Subject analysis set title 
week 48  B cell rich Rituximab


Subject analysis set type 
Per protocol  
Subject analysis set description 
Subgroup of patients classified as B cell rich by histology classification and analysed as PP at week 48


Subject analysis set title 
week 48  B cell rich Tocilizumab


Subject analysis set type 
Per protocol  
Subject analysis set description 
Subgroup of patients classified as B cell rich by histology classification and analysed as PP at week 48


Subject analysis set title 
RTX+TOC, B cell poor, 16 weeks after


Subject analysis set type 
Per protocol  
Subject analysis set description 
B cell poor patients who were non responders at visit 78 were switched to the other IMP and response was evaluated 16 weeks after this switch


Subject analysis set title 
RTX+TOC, B cell rich, 16 weeks after


Subject analysis set type 
Per protocol  
Subject analysis set description 
B cell rich patients who were non responders at visit 78 were switched to the other IMP and response was evaluated 16 weeks after this switch


Subject analysis set title 
TOC+RTX, B cell poor, 16 weeks after


Subject analysis set type 
Per protocol  
Subject analysis set description 
B cell poor patients who were non responders at visit 78 were switched to the other IMP and response was evaluated 16 weeks after this switch


Subject analysis set title 
TOC+RTX, B cell rich, 16 weeks after


Subject analysis set type 
Per protocol  
Subject analysis set description 
B cell rich patients who were non responders at visit 78 were switched to the other IMP and response was evaluated 16 weeks after this switch



End point title 
CDAI 50% Improvement  
End point description 
Patients are deemed as Responders if their CDAI decreased by 50% or more from baseline


End point type 
Primary


End point timeframe 
Period 2: Baseline to Week 16
Period 3: Week 16 to Week 48




Statistical analysis title 
Primary: TOC vs. RTX, B cell poor, ITT  
Comparison groups 
ITT week 16  B cell poor Rituximab v ITT week 16  B cell poor Tocilizumab


Number of subjects included in analysis 
79


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.31  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.114


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.106  
upper limit 
0.333  
Statistical analysis title 
TOC vs. RTX, B cell rich, ITT  
Comparison groups 
ITT week 16  B cell rich Rituximab v ITT week 16  B cell rich Tocilizumab


Number of subjects included in analysis 
64


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.33  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.122


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.12  
upper limit 
0.365  
Statistical analysis title 
TOC vs. RTX, B cell poor (RNAseq), ITT  
Comparison groups 
ITT week 16  B cell poor (RNA_seq) Rituximab v ITT week 16  B cell poor (RNA_seq) Tocilizumab


Number of subjects included in analysis 
65


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.035  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.261


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.027  
upper limit 
0.496  
Statistical analysis title 
TOC vs. RTX, B cell rich (RNAseq), ITT  
Comparison groups 
ITT week 16  B cell rich (RNA_seq) Rituximab v ITT week 16  B cell rich (RNA_seq) Tocilizumab


Number of subjects included in analysis 
59


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.89  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.017


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.272  
upper limit 
0.238  
Statistical analysis title 
TOC vs. RTX, B cell poor, PP  
Comparison groups 
PP week 16  B cell poor Rituximab v PP week 16  B cell poor Tocilizumab


Number of subjects included in analysis 
67


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.029  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.268


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.039  
upper limit 
0.496  
Statistical analysis title 
TOC vs. RTX, B cell rich, PP  
Comparison groups 
PP week 16  B cell rich Rituximab v PP week 16  B cell rich Tocilizumab


Number of subjects included in analysis 
54


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.32  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.135


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.132  
upper limit 
0.401  
Statistical analysis title 
TOC vs. RTX, B cell poor (RNAseq), PP  
Comparison groups 
PP week 16  B cell poor (RNA_seq) Rituximab v PP week 16  B cell poor (RNA_seq) Tocilizumab


Number of subjects included in analysis 
57


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0018  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.416


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.181  
upper limit 
0.651  
Statistical analysis title 
TOC vs. RTX, B cell rich (RNAseq), PP  
Comparison groups 
PP week 16  B cell rich (RNA_seq) RItuximab v PP week 16  B cell rich (RNA_seq) Tocilizumab


Number of subjects included in analysis 
47


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.86  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.026


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.317  
upper limit 
0.265  
Statistical analysis title 
RTX+TOC vs. TOC+RTX, B cell poor, week 16/20 +16  
Statistical analysis description 
Comparison of response in oatients who switched treatment


Comparison groups 
RTX+TOC, B cell poor, 16 weeks after v TOC+RTX, B cell poor, 16 weeks after


Number of subjects included in analysis 
22


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 1  
Method 
Fisher exact  
Confidence interval 

Statistical analysis title 
RTX+TOC vs. TOC+RTX, B cell rich, week 16/20 + 16  
Statistical analysis description 
Comparison of response in patients who switched treatment


Comparison groups 
RTX+TOC, B cell rich, 16 weeks after v TOC+RTX, B cell rich, 16 weeks after


Number of subjects included in analysis 
20


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 1  
Method 
Fisher exact  
Confidence interval 

Statistical analysis title 
TOC vs. RTX, B cell poor, week 24  
Comparison groups 
week 24  B cell poor Rituximab v week 24  B cell poor Tocilizumab


Number of subjects included in analysis 
48


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.05  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.284


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.022  
upper limit 
0.546  
Statistical analysis title 
TOC vs. RTX, B cell rich, week 24  
Comparison groups 
week 24  B cell rich Rituximab v week 24  B cell rich Tocilizumab


Number of subjects included in analysis 
38


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
> 0.05  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.181


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.122  
upper limit 
0.484  
Statistical analysis title 
TOC vs. RTX, B cell poor, week 36  
Comparison groups 
week 36  B cell poor Rituximab v week 36  B cell poor Tocilizumab


Number of subjects included in analysis 
42


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.05  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.027


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.247  
upper limit 
0.301  
Statistical analysis title 
TOC vs. RTX, B cell rich, week 36  
Comparison groups 
week 36  B cell rich Rituximab v week 36  B cell rich Tocilizumab


Number of subjects included in analysis 
33


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
> 0.05  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.267


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.003  
upper limit 
0.537  
Statistical analysis title 
TOC vs. RTX, B cell poor, week 48  
Comparison groups 
week 48  B cell poor Rituximab v week 48  B cell poor Tocilizumab


Number of subjects included in analysis 
38


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
> 0.05  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.082


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.315  
upper limit 
0.15  
Statistical analysis title 
TOC vs. RTX, B cell rich, week 48  
Comparison groups 
week 48  B cell rich Rituximab v week 48  B cell rich Tocilizumab


Number of subjects included in analysis 
33


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
> 0.05  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.283


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.022  
upper limit 
0.588  
Statistical analysis title 
TOC vs. RTX, week 16  
Statistical analysis description 
Any pathotype


Comparison groups 
Rituximab v Tocilizumab


Number of subjects included in analysis 
161


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.05  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.106


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.048  
upper limit 
0.259  
Statistical analysis title 
TOC vs. RTX, week 48  
Statistical analysis description 
Any pathotype


Comparison groups 
Rituximab v Tocilizumab


Number of subjects included in analysis 
84


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.05  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.091


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.092  
upper limit 
0.273 


End point title 
Ultrasound Power Doppler 12max score, change from baseline  
End point description 

End point type 
Primary


End point timeframe 
Timeframe 2: Week 16
Timeframe 3: Week 48




Statistical analysis title 
TOC vs. RTX, B cell poor, ITT  
Comparison groups 
ITT week 16  B cell poor Rituximab v ITT week 16  B cell poor Tocilizumab


Number of subjects included in analysis 
79


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.4  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.1  
upper limit 
4.8  
Statistical analysis title 
TOC vs. RTX, B cell rich, ITT  
Comparison groups 
ITT week 16  B cell rich Rituximab v ITT week 16  B cell rich Tocilizumab


Number of subjects included in analysis 
64


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.38  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.8  
upper limit 
4.6  
Statistical analysis title 
TOC vs. RTX, B cell poor (RNA seq), ITT  
Comparison groups 
ITT week 16  B cell poor (RNA_seq) Rituximab v ITT week 16  B cell poor (RNA_seq) Tocilizumab


Number of subjects included in analysis 
65


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.41  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.1  
upper limit 
4.7  
Statistical analysis title 
TOC vs. RTX, B cell rich (RNA seq), ITT  
Comparison groups 
ITT week 16  B cell rich (RNA_seq) Rituximab v ITT week 16  B cell rich (RNA_seq) Tocilizumab


Number of subjects included in analysis 
59


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.25  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
2.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.8  
upper limit 
6.4  
Statistical analysis title 
TOC vs. RTX, B cell poor, PP  
Comparison groups 
PP week 16  B cell poor Rituximab v PP week 16  B cell poor Tocilizumab


Number of subjects included in analysis 
67


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.19  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
2.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.5  
upper limit 
6.5  
Statistical analysis title 
TOC vs. RTX, B cell rich, PP  
Comparison groups 
PP week 16  B cell rich Rituximab v PP week 16  B cell rich Tocilizumab


Number of subjects included in analysis 
54


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.4  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2  
upper limit 
4.9  
Statistical analysis title 
TOC vs. RTX, B cell poor (RNA seq), PP  
Comparison groups 
PP week 16  B cell poor (RNA_seq) Rituximab v PP week 16  B cell poor (RNA_seq) Tocilizumab


Number of subjects included in analysis 
57


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.34  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.8


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.1  
upper limit 
5.6  
Statistical analysis title 
TOC vs. RTX, B cell rich (RNA seq), PP  
Comparison groups 
PP week 16  B cell rich (RNA_seq) RItuximab v PP week 16  B cell rich (RNA_seq) Tocilizumab


Number of subjects included in analysis 
47


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.29  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
2.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.3  
upper limit 
7.1 


End point title 
Target CDAI (<10.1)  
End point description 

End point type 
Secondary


End point timeframe 
Period 2: Baseline to Week 16
Period 3: Week 16 to Week 48




Statistical analysis title 
TOC vs. RTX, B cell poor, ITT  
Comparison groups 
ITT week 16  B cell poor Rituximab v ITT week 16  B cell poor Tocilizumab


Number of subjects included in analysis 
79


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.11  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.174


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.036  
upper limit 
0.384  
Statistical analysis title 
TOC vs. RTX, B cell rich, ITT  
Comparison groups 
ITT week 16  B cell rich Rituximab v ITT week 16  B cell rich Tocilizumab


Number of subjects included in analysis 
64


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.13  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.175


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.046  
upper limit 
0.396  
Statistical analysis title 
TOC vs. RTX, B cell poor (RNA seq), ITT  
Comparison groups 
ITT week 16  B cell poor (RNA_seq) Rituximab v ITT week 16  B cell poor (RNA_seq) Tocilizumab


Number of subjects included in analysis 
65


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0036  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.348


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.136  
upper limit 
0.561  
Statistical analysis title 
TOC vs. RTX, B cell rich (RNA seq), ITT  
Comparison groups 
ITT week 16  B cell rich (RNA_seq) Rituximab v ITT week 16  B cell rich (RNA_seq) Tocilizumab


Number of subjects included in analysis 
59


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.93  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.011


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.23  
upper limit 
0.253  
Statistical analysis title 
TOC vs. RTX, B cell poor, PP  
Comparison groups 
PP week 16  B cell poor Rituximab v PP week 16  B cell poor Tocilizumab


Number of subjects included in analysis 
67


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.026  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.269


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.039  
upper limit 
0.5  
Statistical analysis title 
TOC vs. RTX, B cell rich, PP  
Comparison groups 
PP week 16  B cell rich Rituximab v PP week 16  B cell rich Tocilizumab


Number of subjects included in analysis 
54


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.32  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.122


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.122  
upper limit 
0.366  
Statistical analysis title 
TOC vs. RTX, B cell poor (RNA seq), PP  
Comparison groups 
PP week 16  B cell poor (RNA_seq) Rituximab v PP week 16  B cell poor (RNA_seq) Tocilizumab


Number of subjects included in analysis 
57


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.00073  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.444


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.214  
upper limit 
0.673  
Statistical analysis title 
TOC vs. RTX, B cell rich (RNA seq), PP  
Comparison groups 
PP week 16  B cell rich (RNA_seq) RItuximab v PP week 16  B cell rich (RNA_seq) Tocilizumab


Number of subjects included in analysis 
47


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.54  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.094


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.36  
upper limit 
0.172 


End point title 
DAS28 (ESR) <= 3.2  
End point description 

End point type 
Secondary


End point timeframe 
Timeframe 2: Week 16
Timeframe 3: Week 48




Statistical analysis title 
TOC vs. RTX, B cell poor, ITT  
Comparison groups 
ITT week 16  B cell poor Rituximab v ITT week 16  B cell poor Tocilizumab


Number of subjects included in analysis 
79


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.1  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.176


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.031  
upper limit 
0.382  
Statistical analysis title 
TOC vs. RTX, B cell rich, ITT  
Comparison groups 
ITT week 16  B cell rich Rituximab v ITT week 16  B cell rich Tocilizumab


Number of subjects included in analysis 
64


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.13  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.177


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.05  
upper limit 
0.404  
Statistical analysis title 
TOC vs. RTX, B cell poor (RNA seq), ITT  
Comparison groups 
ITT week 16  B cell poor (RNA_seq) Rituximab v ITT week 16  B cell poor (RNA_seq) Tocilizumab


Number of subjects included in analysis 
65


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0032  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.349


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.132  
upper limit 
0.567  
Statistical analysis title 
TOC vs. RTX, B cell rich (RNA seq), ITT  
Comparison groups 
ITT week 16  B cell rich (RNA_seq) Tocilizumab v ITT week 16  B cell rich (RNA_seq) Rituximab


Number of subjects included in analysis 
59


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.71  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.045


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.194  
upper limit 
0.283  
Statistical analysis title 
TOC vs. RTX, B cell poor, PP  
Comparison groups 
PP week 16  B cell poor Rituximab v PP week 16  B cell poor Tocilizumab


Number of subjects included in analysis 
67


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.095  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.196


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.032  
upper limit 
0.425  
Statistical analysis title 
TOC vs. RTX, B cell rich, PP  
Comparison groups 
PP week 16  B cell rich Rituximab v PP week 16  B cell rich Tocilizumab


Number of subjects included in analysis 
54


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.094  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.22


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.036  
upper limit 
0.476  
Statistical analysis title 
TOC vs. RTX, B cell poor (RNA seq), PP  
Comparison groups 
PP week 16  B cell poor (RNA_seq) Rituximab v PP week 16  B cell poor (RNA_seq) Tocilizumab


Number of subjects included in analysis 
57


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0014  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.412


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.178  
upper limit 
0.647  
Statistical analysis title 
TOC vs. RTX, B cell rich (RNA seq), PP  
Comparison groups 
PP week 16  B cell rich (RNA_seq) RItuximab v PP week 16  B cell rich (RNA_seq) Tocilizumab


Number of subjects included in analysis 
47


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.74  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.047


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.23  
upper limit 
0.324 


End point title 
DAS28 (CRP) <= 3.2  
End point description 

End point type 
Secondary


End point timeframe 
Timeframe 2: Week 16
Timeframe 3: Week 48




Statistical analysis title 
TOC vs. RTX, B cell poor, ITT  
Comparison groups 
ITT week 16  B cell poor Rituximab v ITT week 16  B cell poor Tocilizumab


Number of subjects included in analysis 
79


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.18  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.148


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.065  
upper limit 
0.36  
Statistical analysis title 
TOC vs. RTX, B cell rich, ITT  
Comparison groups 
ITT week 16  B cell rich Rituximab v ITT week 16  B cell rich Tocilizumab


Number of subjects included in analysis 
64


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.65  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.056


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.183  
upper limit 
0.295  
Statistical analysis title 
TOC vs. RTX, B cell poor (RNA seq), ITT  
Comparison groups 
ITT week 16  B cell poor (RNA_seq) Rituximab v ITT week 16  B cell poor (RNA_seq) Tocilizumab


Number of subjects included in analysis 
65


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.015  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.288


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.065  
upper limit 
0.51  
Statistical analysis title 
TOC vs. RTX, B cell rich (RNA seq), ITT  
Comparison groups 
ITT week 16  B cell rich (RNA_seq) Rituximab v ITT week 16  B cell rich (RNA_seq) Tocilizumab


Number of subjects included in analysis 
59


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.5  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.087


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.338  
upper limit 
0.164  
Statistical analysis title 
TOC vs. RTX, B cell poor, PP  
Comparison groups 
PP week 16  B cell poor Rituximab v PP week 16  B cell poor Tocilizumab


Number of subjects included in analysis 
67


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.085  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.209


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.025  
upper limit 
0.443  
Statistical analysis title 
TOC vs. RTX, B cell rich, PP  
Comparison groups 
PP week 16  B cell rich Rituximab v PP week 16  B cell rich Tocilizumab


Number of subjects included in analysis 
54


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.4  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.112


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.149  
upper limit 
0.373  
Statistical analysis title 
TOC vs. RTX, B cell poor (RNA seq), PP  
Comparison groups 
PP week 16  B cell poor (RNA_seq) Rituximab v PP week 16  B cell poor (RNA_seq) Tocilizumab


Number of subjects included in analysis 
57


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0033  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.381


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.142  
upper limit 
0.621  
Statistical analysis title 
TOC vs. RTX, B cell rich (RNA seq), PP  
Comparison groups 
PP week 16  B cell rich (RNA_seq) RItuximab v PP week 16  B cell rich (RNA_seq) Tocilizumab


Number of subjects included in analysis 
47


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.68  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.06


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.344  
upper limit 
0.224 


End point title 
DAS28 (ESR) <= 2.6  
End point description 

End point type 
Secondary


End point timeframe 
Timeframe 2: Week 16
Timeframe 3: Week 48




Statistical analysis title 
TOC vs. RTX, B cell poor, ITT  
Comparison groups 
ITT week 16  B cell poor Tocilizumab v ITT week 16  B cell poor Rituximab


Number of subjects included in analysis 
79


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.037  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.208


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.02  
upper limit 
0.396  
Statistical analysis title 
TOC vs. RTX, B cell rich, ITT  
Comparison groups 
ITT week 16  B cell rich Rituximab v ITT week 16  B cell rich Tocilizumab


Number of subjects included in analysis 
64


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0047  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.294


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.107  
upper limit 
0.481  
Statistical analysis title 
TOC vs. RTX, B cell poor (RNA seq), ITT  
Comparison groups 
ITT week 16  B cell poor (RNA_seq) Rituximab v ITT week 16  B cell poor (RNA_seq) Tocilizumab


Number of subjects included in analysis 
65


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.004  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.315


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.119  
upper limit 
0.512  
Statistical analysis title 
TOC vs. RTX, B cell rich (RNA seq), ITT  
Comparison groups 
ITT week 16  B cell rich (RNA_seq) Rituximab v ITT week 16  B cell rich (RNA_seq) Tocilizumab


Number of subjects included in analysis 
59


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.03  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.245


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.041  
upper limit 
0.448  
Statistical analysis title 
TOC vs. RTX, B cell poor, PP  
Comparison groups 
PP week 16  B cell poor Rituximab v PP week 16  B cell poor Tocilizumab


Number of subjects included in analysis 
67


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.014  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.271


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.058  
upper limit 
0.485  
Statistical analysis title 
TOC vs. RTX, B cell rich, PP  
Comparison groups 
PP week 16  B cell rich Rituximab v PP week 16  B cell rich Tocilizumab


Number of subjects included in analysis 
54


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0052  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.327


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.109  
upper limit 
0.544  
Statistical analysis title 
TOC vs. RTX, B cell poor (RNA seq), PP  
Comparison groups 
PP week 16  B cell poor (RNA_seq) Rituximab v PP week 16  B cell poor (RNA_seq) Tocilizumab


Number of subjects included in analysis 
57


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0019  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.386


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.166  
upper limit 
0.607  
Statistical analysis title 
TOC vs. RTX, B cell rich (RNA seq), PP  
Comparison groups 
PP week 16  B cell rich (RNA_seq) RItuximab v PP week 16  B cell rich (RNA_seq) Tocilizumab


Number of subjects included in analysis 
47


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.066  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.261


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.016  
upper limit 
0.507 


End point title 
DAS28 (CRP) <= 2.6  
End point description 

End point type 
Secondary


End point timeframe 
Timeframe 2: Week 16
Timeframe 3: Week 48




Statistical analysis title 
TOC vs. RTX, B cell poor, ITT  
Comparison groups 
ITT week 16  B cell poor Rituximab v ITT week 16  B cell poor Tocilizumab


Number of subjects included in analysis 
79


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.17  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.133


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.055  
upper limit 
0.321  
Statistical analysis title 
TOC vs. RTX, B cell rich, ITT  
Comparison groups 
ITT week 16  B cell rich Rituximab v ITT week 16  B cell rich Tocilizumab


Number of subjects included in analysis 
64


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.12  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.169


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.026  
upper limit 
0.364  
Statistical analysis title 
TOC vs. RTX, B cell poor (RNA seq), ITT  
Comparison groups 
ITT week 16  B cell poor (RNA_seq) Rituximab v ITT week 16  B cell poor (RNA_seq) Tocilizumab


Number of subjects included in analysis 
65


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.076  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.191


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.04  
upper limit 
0.387  
Statistical analysis title 
TOC vs. RTX, B cell rich (RNA seq), ITT  
Comparison groups 
ITT week 16  B cell rich (RNA_seq) Rituximab v ITT week 16  B cell rich (RNA_seq) Tocilizumab


Number of subjects included in analysis 
59


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.21  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.143


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.061  
upper limit 
0.346  
Statistical analysis title 
TOC vs. RTX, B cell poor, PP  
Comparison groups 
PP week 16  B cell poor Rituximab v PP week 16  B cell poor Tocilizumab


Number of subjects included in analysis 
67


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.1  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.177


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.036  
upper limit 
0.391  
Statistical analysis title 
TOC vs. RTX, B cell rich, PP  
Comparison groups 
PP week 16  B cell rich Rituximab v PP week 16  B cell rich Tocilizumab


Number of subjects included in analysis 
54


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.17  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.175


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.047  
upper limit 
0.397  
Statistical analysis title 
TOC vs. RTX, B cell poor (RNA seq), PP  
Comparison groups 
PP week 16  B cell poor (RNA_seq) Rituximab v PP week 16  B cell poor (RNA_seq) Tocilizumab


Number of subjects included in analysis 
57


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.056  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.235


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.015  
upper limit 
0.455  
Statistical analysis title 
TOC vs. RTX, B cell rich (RNA seq), PP  
Comparison groups 
PP week 16  B cell rich (RNA_seq) RItuximab v PP week 16  B cell rich (RNA_seq) Tocilizumab


Number of subjects included in analysis 
47


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.45  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.12


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.116  
upper limit 
0.357  
Statistical analysis title 
TOC vs. RTX, B cell rich (RNA seq), PP  
Comparison groups 
PP week 16  B cell rich (RNA_seq) RItuximab v PP week 16  B cell rich (RNA_seq) Tocilizumab


Number of subjects included in analysis 
47


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.45  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.12


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.116  
upper limit 
0.357 


End point title 
Good/Moderate EULAR DAS28 (ESR) response  
End point description 

End point type 
Secondary


End point timeframe 
Timeframe 2: Week 16
Timeframe 3: Week 48




Statistical analysis title 
TOC vs. RTX, B cell poor, ITT  
Comparison groups 
ITT week 16  B cell poor Rituximab v ITT week 16  B cell poor Tocilizumab


Number of subjects included in analysis 
79


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.031  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.22


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.039  
upper limit 
0.401  
Statistical analysis title 
TOC vs. RTX, B cell rich, ITT  
Comparison groups 
ITT week 16  B cell rich Rituximab v ITT week 16  B cell rich Tocilizumab


Number of subjects included in analysis 
64


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.34  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.113


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.075  
upper limit 
0.301  
Statistical analysis title 
TOC vs. RTX, B cell poor (RNA seq), ITT  
Comparison groups 
ITT week 16  B cell poor (RNA_seq) Rituximab v ITT week 16  B cell poor (RNA_seq) Tocilizumab


Number of subjects included in analysis 
65


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0053  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.301


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.117  
upper limit 
0.485  
Statistical analysis title 
TOC vs. RTX, B cell rich (RNA seq), ITT  
Comparison groups 
ITT week 16  B cell rich (RNA_seq) Rituximab v ITT week 16  B cell rich (RNA_seq) Tocilizumab


Number of subjects included in analysis 
59


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 1  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.028


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.171  
upper limit 
0.226  
Statistical analysis title 
TOC vs. RTX, B cell poor, PP  
Comparison groups 
PP week 16  B cell poor Rituximab v PP week 16  B cell poor Tocilizumab


Number of subjects included in analysis 
67


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0018  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.318


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.151  
upper limit 
0.485  
Statistical analysis title 
TOC vs. RTX, B cell rich, PP  
Comparison groups 
PP week 16  B cell rich Rituximab v PP week 16  B cell rich Tocilizumab


Number of subjects included in analysis 
54


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.16  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.171


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.021  
upper limit 
0.363  
Statistical analysis title 
TOC vs. RTX, B cell poor (RNA seq), PP  
Comparison groups 
PP week 16  B cell poor (RNA_seq) Rituximab v PP week 16  B cell poor (RNA_seq) Tocilizumab


Number of subjects included in analysis 
57


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.00053  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.375


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.207  
upper limit 
0.543  
Statistical analysis title 
TOC vs. RTX, B cell rich (RNA seq), PP  
Comparison groups 
PP week 16  B cell rich (RNA_seq) RItuximab v PP week 16  B cell rich (RNA_seq) Tocilizumab


Number of subjects included in analysis 
47


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.44  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.109


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.096  
upper limit 
0.314 


End point title 
Good/Moderate EULAR DAS28 (CRP) response  
End point description 

End point type 
Secondary


End point timeframe 
Timeframe 2: Week 16
Timeframe 3: Week 48




Statistical analysis title 
TOC vs. RTX, B cell poor, ITT  
Comparison groups 
ITT week 16  B cell poor Tocilizumab v ITT week 16  B cell poor Rituximab


Number of subjects included in analysis 
79


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.054  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.202


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0  
upper limit 
0.403  
Statistical analysis title 
TOC vs. RTX, B cell rich, ITT  
Comparison groups 
ITT week 16  B cell rich Rituximab v ITT week 16  B cell rich Tocilizumab


Number of subjects included in analysis 
64


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.31  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.109


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.1  
upper limit 
0.319  
Statistical analysis title 
TOC vs. RTX, B cell poor (RNA seq), ITT  
Comparison groups 
ITT week 16  B cell poor (RNA_seq) Rituximab v ITT week 16  B cell poor (RNA_seq) Tocilizumab


Number of subjects included in analysis 
65


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.015  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.298


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.087  
upper limit 
0.51  
Statistical analysis title 
TOC vs. RTX, B cell rich (RNA seq), ITT  
Comparison groups 
ITT week 16  B cell rich (RNA_seq) Rituximab v ITT week 16  B cell rich (RNA_seq) Tocilizumab


Number of subjects included in analysis 
59


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.81  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.026


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.185  
upper limit 
0.238  
Statistical analysis title 
TOC vs. RTX, B cell poor, PP  
Comparison groups 
PP week 16  B cell poor Rituximab v PP week 16  B cell poor Tocilizumab


Number of subjects included in analysis 
67


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0029  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.332


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.14  
upper limit 
0.525  
Statistical analysis title 
TOC vs. RTX, B cell rich, PP  
Comparison groups 
PP week 16  B cell rich Rituximab v PP week 16  B cell rich Tocilizumab


Number of subjects included in analysis 
54


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.54  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.105


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.13  
upper limit 
0.341  
Statistical analysis title 
TOC vs. RTX, B cell poor (RNA seq), PP  
Comparison groups 
PP week 16  B cell poor (RNA_seq) Rituximab v PP week 16  B cell poor (RNA_seq) Tocilizumab


Number of subjects included in analysis 
57


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0015  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.389


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.186  
upper limit 
0.592  
Statistical analysis title 
TOC vs. RTX, B cell rich (RNA seq), PP  
Comparison groups 
PP week 16  B cell rich (RNA_seq) RItuximab v PP week 16  B cell rich (RNA_seq) Tocilizumab


Number of subjects included in analysis 
47


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 1  
Method 
Chisquared corrected  
Parameter type 
Risk difference (RD)  
Point estimate 
0.039


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.204  
upper limit 
0.283 


End point title 
CDAI, change from baseline  
End point description 

End point type 
Secondary


End point timeframe 
Timeframe 2: Week 16
Timeframe 3: Week 48




Statistical analysis title 
TOC vs. RTX, B cell poor, ITT  
Comparison groups 
ITT week 16  B cell poor Rituximab v ITT week 16  B cell poor Tocilizumab


Number of subjects included in analysis 
79


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.18  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
3.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.7  
upper limit 
8.9  
Statistical analysis title 
TOC vs. RTX, B cell rich, ITT  
Comparison groups 
ITT week 16  B cell rich Rituximab v ITT week 16  B cell rich Tocilizumab


Number of subjects included in analysis 
64


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.73  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4.9  
upper limit 
6.9  
Statistical analysis title 
TOC vs. RTX, B cell poor (RNAseq), ITT  
Comparison groups 
ITT week 16  B cell poor (RNA_seq) Rituximab v ITT week 16  B cell poor (RNA_seq) Tocilizumab


Number of subjects included in analysis 
65


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.029  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
6.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.7  
upper limit 
12  
Statistical analysis title 
TOC vs. RTX, B cell rich (RNAseq), ITT  
Comparison groups 
ITT week 16  B cell rich (RNA_seq) Rituximab v ITT week 16  B cell rich (RNA_seq) Tocilizumab


Number of subjects included in analysis 
59


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.88  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
6.5  
upper limit 
5.6  
Statistical analysis title 
TOC vs. RTX, B cell poor, PP  
Comparison groups 
PP week 16  B cell poor Rituximab v PP week 16  B cell poor Tocilizumab


Number of subjects included in analysis 
67


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.043  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.2  
upper limit 
11.7  
Statistical analysis title 
TOC vs. RTX, B cell rich, PP  
Comparison groups 
PP week 16  B cell rich Rituximab v PP week 16  B cell rich Tocilizumab


Number of subjects included in analysis 
54


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.93  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
6.7  
upper limit 
6.2  
Statistical analysis title 
TOC vs. RTX, B cell poor (RNAseq), PP  
Comparison groups 
PP week 16  B cell poor (RNA_seq) Rituximab v PP week 16  B cell poor (RNA_seq) Tocilizumab


Number of subjects included in analysis 
57


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0097  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
7.9


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2  
upper limit 
13.8  
Statistical analysis title 
TOC vs. RTX, B cell rich (RNAseq), PP  
Comparison groups 
PP week 16  B cell rich (RNA_seq) RItuximab v PP week 16  B cell rich (RNA_seq) Tocilizumab


Number of subjects included in analysis 
47


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.58  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.9


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
8.8  
upper limit 
5 


End point title 
DAS28 (ESR), change from baseline  
End point description 

End point type 
Secondary


End point timeframe 
Timeframe 2: Week 16
Timeframe 3: Week 48




Statistical analysis title 
TOC vs. RTX, B cell poor, ITT  
Comparison groups 
ITT week 16  B cell poor Tocilizumab v ITT week 16  B cell poor Rituximab


Number of subjects included in analysis 
79


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.00063  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.5  
upper limit 
1.7  
Statistical analysis title 
TOC vs. RTX, B cell rich, ITT  
Comparison groups 
ITT week 16  B cell rich Rituximab v ITT week 16  B cell rich Tocilizumab


Number of subjects included in analysis 
64


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.00088  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.5  
upper limit 
1.7  
Statistical analysis title 
TOC vs. RTX, B cell poor (RNA seq), ITT  
Comparison groups 
ITT week 16  B cell poor (RNA_seq) Rituximab v ITT week 16  B cell poor (RNA_seq) Tocilizumab


Number of subjects included in analysis 
65


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.000012  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.9  
upper limit 
2.2  
Statistical analysis title 
TOC vs. RTX, B cell rich (RNA seq), ITT  
Comparison groups 
ITT week 16  B cell rich (RNA_seq) Rituximab v ITT week 16  B cell rich (RNA_seq) Tocilizumab


Number of subjects included in analysis 
59


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.026  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.7


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.1  
upper limit 
1.4  
Statistical analysis title 
TOC vs. RTX, B cell poor, PP  
Comparison groups 
PP week 16  B cell poor Rituximab v PP week 16  B cell poor Tocilizumab


Number of subjects included in analysis 
67


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.000053  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.7  
upper limit 
2  
Statistical analysis title 
TOC vs. RTX, B cell rich, PP  
Comparison groups 
PP week 16  B cell rich Rituximab v PP week 16  B cell rich Tocilizumab


Number of subjects included in analysis 
54


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.00095  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.5  
upper limit 
1.9  
Statistical analysis title 
TOC vs. RTX, B cell poor (RNA seq), PP  
Comparison groups 
PP week 16  B cell poor (RNA_seq) Rituximab v PP week 16  B cell poor (RNA_seq) Tocilizumab


Number of subjects included in analysis 
57


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.000004  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.7


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1  
upper limit 
2.4  
Statistical analysis title 
TOC vs. RTX, B cell rich (RNA seq), PP  
Comparison groups 
PP week 16  B cell rich (RNA_seq) RItuximab v PP week 16  B cell rich (RNA_seq) Tocilizumab


Number of subjects included in analysis 
47


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.03  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.8


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.1  
upper limit 
1.5 


End point title 
DAS28 (CRP), change from baseline  
End point description 

End point type 
Secondary


End point timeframe 
Timeframe 2: Week 16
Timeframe 3: Week 48




Statistical analysis title 
TOC vs. RTX, B cell poor, ITT  
Comparison groups 
ITT week 16  B cell poor Rituximab v ITT week 16  B cell poor Tocilizumab


Number of subjects included in analysis 
79


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.032  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.7


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.1  
upper limit 
1.3  
Statistical analysis title 
TOC vs. RTX, B cell rich, ITT  
Comparison groups 
ITT week 16  B cell rich Rituximab v ITT week 16  B cell rich Tocilizumab


Number of subjects included in analysis 
64


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.059  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0  
upper limit 
1.1  
Statistical analysis title 
TOC vs. RTX, B cell poor (RNA seq), ITT  
Comparison groups 
ITT week 16  B cell poor (RNA_seq) Rituximab v ITT week 16  B cell poor (RNA_seq) Tocilizumab


Number of subjects included in analysis 
65


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0021  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.4  
upper limit 
1.6  
Statistical analysis title 
TOC vs. RTX, B cell rich (RNA seq), ITT  
Comparison groups 
ITT week 16  B cell rich (RNA_seq) Rituximab v ITT week 16  B cell rich (RNA_seq) Tocilizumab


Number of subjects included in analysis 
59


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.34  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.3  
upper limit 
0.9  
Statistical analysis title 
TOC vs. RTX, B cell poor, PP  
Comparison groups 
PP week 16  B cell poor Rituximab v PP week 16  B cell poor Tocilizumab


Number of subjects included in analysis 
67


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.0054  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.9


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.3  
upper limit 
1.5  
Statistical analysis title 
TOC vs. RTX, B cell rich, PP  
Comparison groups 
PP week 16  B cell rich Rituximab v PP week 16  B cell rich Tocilizumab


Number of subjects included in analysis 
54


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.076  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.1  
upper limit 
1.2  
Statistical analysis title 
TOC vs. RTX, B cell poor (RNA seq), PP  
Comparison groups 
PP week 16  B cell poor (RNA_seq) Rituximab v PP week 16  B cell poor (RNA_seq) Tocilizumab


Number of subjects included in analysis 
57


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.00033  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.6  
upper limit 
1.9  
Statistical analysis title 
TOC vs. RTX, B cell rich (RNA seq), PP  
Comparison groups 
PP week 16  B cell rich (RNA_seq) RItuximab v PP week 16  B cell rich (RNA_seq) Tocilizumab


Number of subjects included in analysis 
47


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.47  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.4  
upper limit 
0.9 


End point title 
HAQ score, change from baseline  
End point description 

End point type 
Secondary


End point timeframe 
Timeframe 2: Week 16
Timeframe 3: Week 48




Statistical analysis title 
TOC vs. RTX, B cell poor, ITT  
Comparison groups 
ITT week 16  B cell poor Rituximab v ITT week 16  B cell poor Tocilizumab


Number of subjects included in analysis 
79


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.4  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.1  
upper limit 
0.3  
Statistical analysis title 
TOC vs. RTX, B cell rich, ITT  
Comparison groups 
ITT week 16  B cell rich Rituximab v ITT week 16  B cell rich Tocilizumab


Number of subjects included in analysis 
64


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.41  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.2  
upper limit 
0.4  
Statistical analysis title 
TOC vs. RTX, B cell poor (RNA seq), ITT  
Comparison groups 
ITT week 16  B cell poor (RNA_seq) Rituximab v ITT week 16  B cell poor (RNA_seq) Tocilizumab


Number of subjects included in analysis 
65


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.91  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.2  
upper limit 
0.2  
Statistical analysis title 
TOC vs. RTX, B cell rich (RNA seq), ITT  
Comparison groups 
ITT week 16  B cell rich (RNA_seq) Rituximab v ITT week 16  B cell rich (RNA_seq) Tocilizumab


Number of subjects included in analysis 
59


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.085  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0  
upper limit 
0.5  
Statistical analysis title 
TOC vs. RTX, B cell poor, PP  
Comparison groups 
PP week 16  B cell poor Rituximab v PP week 16  B cell poor Tocilizumab


Number of subjects included in analysis 
67


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.26  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.1  
upper limit 
0.4  
Statistical analysis title 
TOC vs. RTX, B cell rich, PP  
Comparison groups 
PP week 16  B cell rich Rituximab v PP week 16  B cell rich Tocilizumab


Number of subjects included in analysis 
54


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.88  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.2  
upper limit 
0.3  
Statistical analysis title 
TOC vs. RTX, B cell poor (RNA seq), PP  
Comparison groups 
PP week 16  B cell poor (RNA_seq) Rituximab v PP week 16  B cell poor (RNA_seq) Tocilizumab


Number of subjects included in analysis 
57


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.86  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.2  
upper limit 
0.3  
Statistical analysis title 
TOC vs. RTX, B cell rich (RNA seq), PP  
Comparison groups 
PP week 16  B cell rich (RNA_seq) RItuximab v PP week 16  B cell rich (RNA_seq) Tocilizumab


Number of subjects included in analysis 
47


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.24  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.1  
upper limit 
0.4 


End point title 
FACIT score, change from baseline  
End point description 

End point type 
Secondary


End point timeframe 
Timeframe 2: Week 16
Timeframe 3: Week 48




Statistical analysis title 
TOC vs. RTX, B cell poor, ITT  
Comparison groups 
ITT week 16  B cell poor Tocilizumab v ITT week 16  B cell poor Rituximab


Number of subjects included in analysis 
79


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.015  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
7.2  
upper limit 
0.8  
Statistical analysis title 
TOC vs. RTX, B cell rich, ITT  
Comparison groups 
ITT week 16  B cell rich Rituximab v ITT week 16  B cell rich Tocilizumab


Number of subjects included in analysis 
64


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.79  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.7


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4.8  
upper limit 
6.3  
Statistical analysis title 
TOC vs. RTX, B cell poor (RNA seq), ITT  
Comparison groups 
ITT week 16  B cell poor (RNA_seq) Rituximab v ITT week 16  B cell poor (RNA_seq) Tocilizumab


Number of subjects included in analysis 
65


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.16  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
2.8


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
6.8  
upper limit 
1.2  
Statistical analysis title 
TOC vs. RTX, B cell rich (RNA seq), ITT  
Comparison groups 
ITT week 16  B cell rich (RNA_seq) Rituximab v ITT week 16  B cell rich (RNA_seq) Tocilizumab


Number of subjects included in analysis 
59


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.58  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
6.6  
upper limit 
3.8  
Statistical analysis title 
TOC vs. RTX, B cell poor, PP  
Comparison groups 
PP week 16  B cell poor Rituximab v PP week 16  B cell poor Tocilizumab


Number of subjects included in analysis 
67


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.021  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
3.8


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
7  
upper limit 
0.6  
Statistical analysis title 
TOC vs. RTX, B cell rich, PP  
Comparison groups 
PP week 16  B cell rich Rituximab v PP week 16  B cell rich Tocilizumab


Number of subjects included in analysis 
54


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.92  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
5.6  
upper limit 
6.2  
Statistical analysis title 
TOC vs. RTX, B cell poor (RNA seq), PP  
Comparison groups 
PP week 16  B cell poor (RNA_seq) Rituximab v PP week 16  B cell poor (RNA_seq) Tocilizumab


Number of subjects included in analysis 
57


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.37  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.9


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
6.2  
upper limit 
2.4  
Statistical analysis title 
TOC vs. RTX, B cell rich (RNA seq), PP  
Comparison groups 
PP week 16  B cell rich (RNA_seq) RItuximab v PP week 16  B cell rich (RNA_seq) Tocilizumab


Number of subjects included in analysis 
47


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.44  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
2.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
7.5  
upper limit 
3.3 


End point title 
Ultrasound synovial Thickness 12max score, change from baseline  
End point description 

End point type 
Secondary


End point timeframe 
Timeframe 2: Week 16
Timeframe 3: Week 48




Statistical analysis title 
TOC vs RTX, B cell poor, ITT  
Comparison groups 
ITT week 16  B cell poor Rituximab v ITT week 16  B cell poor Tocilizumab


Number of subjects included in analysis 
79


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.82  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
5.1  
upper limit 
4.1  
Statistical analysis title 
TOC vs RTX, B cell rich, ITT  
Comparison groups 
ITT week 16  B cell rich Rituximab v ITT week 16  B cell rich Tocilizumab


Number of subjects included in analysis 
64


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.33  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.7  
upper limit 
5  
Statistical analysis title 
TOC vs RTX, B cell poor (RNA seq), ITT  
Comparison groups 
ITT week 16  B cell poor (RNA_seq) Rituximab v ITT week 16  B cell poor (RNA_seq) Tocilizumab


Number of subjects included in analysis 
65


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.16  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
3.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
8.7  
upper limit 
1.6  
Statistical analysis title 
TOC vs RTX, B cell rich (RNA seq), ITT  
Comparison groups 
ITT week 16  B cell rich (RNA_seq) Rituximab v ITT week 16  B cell rich (RNA_seq) Tocilizumab


Number of subjects included in analysis 
59


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.037  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
3.6


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.2  
upper limit 
6.9  
Statistical analysis title 
TOC vs RTX, B cell poor, PP  
Comparison groups 
PP week 16  B cell poor Rituximab v PP week 16  B cell poor Tocilizumab


Number of subjects included in analysis 
67


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.72  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.9


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4.2  
upper limit 
5.9  
Statistical analysis title 
TOC vs RTX, B cell rich, PP  
Comparison groups 
PP week 16  B cell rich Rituximab v PP week 16  B cell rich Tocilizumab


Number of subjects included in analysis 
54


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.36  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.7


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2  
upper limit 
5.4  
Statistical analysis title 
TOC vs RTX, B cell poor (RNA seq), PP  
Comparison groups 
PP week 16  B cell poor (RNA_seq) Rituximab v PP week 16  B cell poor (RNA_seq) Tocilizumab


Number of subjects included in analysis 
57


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.33  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
2.7


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
8.3  
upper limit 
2.9  
Statistical analysis title 
TOC vs RTX, B cell rich (RNA seq), PP  
Comparison groups 
PP week 16  B cell rich (RNA_seq) RItuximab v PP week 16  B cell rich (RNA_seq) Tocilizumab


Number of subjects included in analysis 
47


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.03  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
4.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.5  
upper limit 
8.1 


End point title 
SF36  Physical Component Summary  
End point description 

End point type 
Secondary


End point timeframe 
Timeframe 2: Week 16
Timeframe 3: Week 48




Statistical analysis title 
TOC vs. RTX, B cell poor, ITT  
Comparison groups 
ITT week 16  B cell poor Tocilizumab v ITT week 16  B cell poor Rituximab


Number of subjects included in analysis 
79


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.12  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
3.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
7.4  
upper limit 
0.9  
Statistical analysis title 
TOC vs. RTX, B cell rich, ITT  
Comparison groups 
ITT week 16  B cell rich Rituximab v ITT week 16  B cell rich Tocilizumab


Number of subjects included in analysis 
64


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.59  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
7.2  
upper limit 
4.1  
Statistical analysis title 
TOC vs. RTX, B cell poor (RNA seq), ITT  
Comparison groups 
ITT week 16  B cell poor (RNA_seq) Rituximab v ITT week 16  B cell poor (RNA_seq) Tocilizumab


Number of subjects included in analysis 
65


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.72  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.8


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
5  
upper limit 
3.4  
Statistical analysis title 
TOC vs. RTX, B cell rich (RNA seq), ITT  
Comparison groups 
ITT week 16  B cell rich (RNA_seq) Rituximab v ITT week 16  B cell rich (RNA_seq) Tocilizumab


Number of subjects included in analysis 
59


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.16  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
9.6  
upper limit 
1.6  
Statistical analysis title 
TOC vs. RTX, B cell poor, PP  
Comparison groups 
PP week 16  B cell poor Rituximab v PP week 16  B cell poor Tocilizumab


Number of subjects included in analysis 
67


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.08  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
8.5  
upper limit 
0.5  
Statistical analysis title 
TOC vs. RTX, B cell rich, PP  
Comparison groups 
PP week 16  B cell rich Rituximab v PP week 16  B cell rich Tocilizumab


Number of subjects included in analysis 
54


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.98  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
5.7  
upper limit 
5.5  
Statistical analysis title 
TOC vs. RTX, B cell poor (RNA seq), PP  
Comparison groups 
PP week 16  B cell poor (RNA_seq) Rituximab v PP week 16  B cell poor (RNA_seq) Tocilizumab


Number of subjects included in analysis 
57


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.83  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
5.1  
upper limit 
4.1  
Statistical analysis title 
TOC vs. RTX, B cell rich (RNA seq), PP  
Comparison groups 
PP week 16  B cell rich (RNA_seq) RItuximab v PP week 16  B cell rich (RNA_seq) Tocilizumab


Number of subjects included in analysis 
47


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.33  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
2.7


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
8.2  
upper limit 
2.8 


End point title 
SF36  Mental Component Summary  
End point description 

End point type 
Secondary


End point timeframe 
Timeframe 2: Week 16
Timeframe 3: Week 48




Statistical analysis title 
TOC vs. RTX, B cell poor, ITT  
Comparison groups 
ITT week 16  B cell poor Rituximab v ITT week 16  B cell poor Tocilizumab


Number of subjects included in analysis 
79


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.22  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
2.8


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
7.3  
upper limit 
1.7  
Statistical analysis title 
TOC vs. RTX, B cell rich, ITT  
Comparison groups 
ITT week 16  B cell rich Rituximab v ITT week 16  B cell rich Tocilizumab


Number of subjects included in analysis 
64


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.53  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4.5  
upper limit 
8.5  
Statistical analysis title 
TOC vs. RTX, B cell poor (RNA seq), ITT  
Comparison groups 
ITT week 16  B cell poor (RNA_seq) Rituximab v ITT week 16  B cell poor (RNA_seq) Tocilizumab


Number of subjects included in analysis 
65


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.16  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
3.7


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
8.8  
upper limit 
1.5  
Statistical analysis title 
TOC vs. RTX, B cell rich (RNA seq), ITT  
Comparison groups 
ITT week 16  B cell rich (RNA_seq) Rituximab v ITT week 16  B cell rich (RNA_seq) Tocilizumab


Number of subjects included in analysis 
59


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.68  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.4


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
5.4  
upper limit 
8.2  
Statistical analysis title 
TOC vs. RTX, B cell poor, PP  
Comparison groups 
PP week 16  B cell poor Rituximab v PP week 16  B cell poor Tocilizumab


Number of subjects included in analysis 
67


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.16  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
3.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
8.1  
upper limit 
1.4  
Statistical analysis title 
TOC vs. RTX, B cell rich, PP  
Comparison groups 
PP week 16  B cell rich Rituximab v PP week 16  B cell rich Tocilizumab


Number of subjects included in analysis 
54


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.96  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.2


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
6.7  
upper limit 
7.1  
Statistical analysis title 
TOC vs. RTX, B cell poor (RNA seq), PP  
Comparison groups 
PP week 16  B cell poor (RNA_seq) Rituximab v PP week 16  B cell poor (RNA_seq) Tocilizumab


Number of subjects included in analysis 
57


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.14  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
4.1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
9.6  
upper limit 
1.4  
Statistical analysis title 
TOC vs. RTX, B cell rich (RNA seq), PP  
Comparison groups 
PP week 16  B cell rich (RNA_seq) RItuximab v PP week 16  B cell rich (RNA_seq) Tocilizumab


Number of subjects included in analysis 
47


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
= 0.78  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
8.4  
upper limit 
6.3 


End point title 
SHSS total score, change from baseline  
End point description 

End point type 
Secondary


End point timeframe 
Week 24
Week 48




Statistical analysis title 
TOC vs. RTX, B cell poor, week 24  
Comparison groups 
week 24  B cell poor Rituximab v week 24  B cell poor Tocilizumab


Number of subjects included in analysis 
48


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
> 0.05  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.12


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.61  
upper limit 
0.38  
Statistical analysis title 
TOC vs. RTX, B cell rich, week 24  
Comparison groups 
week 24  B cell rich Rituximab v week 24  B cell rich Tocilizumab


Number of subjects included in analysis 
38


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
> 0.05  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.06


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.52  
upper limit 
0.64  
Statistical analysis title 
TOC vs. RTX, B cell rich, week 48  
Comparison groups 
week 48  B cell rich Rituximab v week 48  B cell rich Tocilizumab


Number of subjects included in analysis 
33


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
> 0.05  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.11


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.51  
upper limit 
0.73  
Statistical analysis title 
TOC vs. RTX, B cell poor, week 48  
Comparison groups 
week 48  B cell poor Tocilizumab v week 48  B cell poor Rituximab


Number of subjects included in analysis 
38


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
> 0.05  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
1.14


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.02  
upper limit 
0.75 


End point title 
SHSS Erosion score, change from baseline  
End point description 

End point type 
Secondary


End point timeframe 
Week 24
Week 48




Statistical analysis title 
TOC vs. RTX, B cell poor, week 24  
Comparison groups 
week 24  B cell poor Rituximab v week 24  B cell poor Tocilizumab


Number of subjects included in analysis 
48


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
> 0.05  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.26


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.89  
upper limit 
0.37  
Statistical analysis title 
TOC vs. RTX, B cell poor, week 48  
Comparison groups 
week 48  B cell poor Rituximab v week 48  B cell poor Tocilizumab


Number of subjects included in analysis 
38


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
> 0.05  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.25


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.04  
upper limit 
0.55  
Statistical analysis title 
TOC vs. RTX, B cell rich, week 24  
Comparison groups 
week 24  B cell rich Rituximab v week 24  B cell rich Tocilizumab


Number of subjects included in analysis 
38


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
> 0.05  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.33


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.14  
upper limit 
0.79  
Statistical analysis title 
TOC vs. RTX, B cell rich, week 48  
Comparison groups 
week 48  B cell rich Rituximab v week 48  B cell rich Tocilizumab


Number of subjects included in analysis 
33


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
> 0.05  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.31


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.23  
upper limit 
0.85 


End point title 
SHSS Joint Space Narrowing score  
End point description 

End point type 
Secondary


End point timeframe 
Week 24
Week 48




Statistical analysis title 
TOC vs. RTX, B cell poor, week 24  
Comparison groups 
week 24  B cell poor Rituximab v week 24  B cell poor Tocilizumab


Number of subjects included in analysis 
48


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.05  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.69


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.65  
upper limit 
0.28  
Statistical analysis title 
TOC vs. RTX, B cell poor, week 48  
Comparison groups 
week 48  B cell poor Rituximab v week 48  B cell poor Tocilizumab


Number of subjects included in analysis 
38


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.05  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.7


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.89  
upper limit 
0.5  
Statistical analysis title 
TOC vs. RTX, B cell rich, week 24  
Comparison groups 
week 24  B cell rich Rituximab v week 24  B cell rich Tocilizumab


Number of subjects included in analysis 
38


Analysis specification 
Prespecified


Analysis type 
superiority  
Pvalue 
< 0.05  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0

