Clinical Trial Results:
Efficacy of Tofacitinib in Reduction of Inflammation Detected on MRI in Patients with Psoriatic ArthritiS PresenTing with Axial InvOlvement - a Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial (PASTOR)

Trial information Top of page
Trial identification
Sponsor protocol code	PASTOR2018
Additional study identifiers
ISRCTN number	-
US NCT number	NCT04062695
WHO universal trial number (UTN)	-
Sponsors
Sponsor organisation name	Charité Universitätsmedizin Berlin
Sponsor organisation address	Cahritéplatz 1, Berlin, Germany, 10117
Public contact	PD Dr. med. Fabian Proft and PD Dr. Hildrun Haibel, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin Medical Department I, Rheumatology, 49 30 450514582, fabian.proft@charite.de
Scientific contact	PD Dr. med. Fabian Proft and PD Dr. Hildrun Haibel, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin Medical Department I, Rheumatology, 49 30 450514582, fabian.proft@charite.de
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	20 Nov 2024
Is this the analysis of the primary completion data?	Yes
Primary completion date	02 May 2024
Global end of trial reached?	Yes
Global end of trial date	02 May 2024
Was the trial ended prematurely?	Yes
General information about the trial
Main objective of the trial	Improvement of the total Berlin MRI score for sacroiliac joints and spine as compared to baseline after 12 weeks of therapy with Tofacitinib or placebo.
Protection of trial subjects	The study was conducted in accordance with the principles of the Declaration of Helsinki (1996).
Background therapy	Psoriatic arthritis (PsA) is a chronic inflammatory disease associated with psoriasis, which is attributed to the group of spondyloarthritides (SpA) and is characterized by the presence of synovitis, enthesitis, dactylitis, and by axial involvement.There is a considerable overlap of PsA with axial SpA in terms of pathophysiology, diagnosis, and classification, however, patients with PsA can also be classified as axial SpA on the basis of their clinical presentation. There are also significant differences between axial PsA and axial SpA in genetics, radiographic features, age at disease onset and clinical progression over time. According to treatment guidelines for axial PsA, the main treatment options in patients with PsA presenting with axial involvement are NSAIDs. If they fail to show sufficient efficacy tumour necrosis factor (TNF) inhibitors or IL-17 inhibitors and newerdays JAK-inhibitors may be considered. The aim of this study was to investigate the efficacy and safety of the JAK inhibitor Tofactinib in axPsA.
Evidence for comparator	-
Actual start date of recruitment	01 Apr 2020
Long term follow-up planned	No
Independent data monitoring committee (IDMC) involvement?	No
Population of trial subjects
Number of subjects enrolled per country
Country: Number of subjects enrolled	Germany: 26
Worldwide total number of subjects	26
EEA total number of subjects	26
Number of subjects enrolled per age group
In utero	0
Preterm newborn - gestational age < 37 wk	0
Newborns (0-27 days)	0
Infants and toddlers (28 days-23 months)	0
Children (2-11 years)	0
Adolescents (12-17 years)	0
Adults (18-64 years)	26
From 65 to 84 years	0
85 years and over	0

Trial information Top of page

Subject disposition Top of page
Recruitment
Recruitment details	Patients were recruited between 12/09/2020 to 04/08/2023 in xx study sites in Germany.
Pre-assignment
Screening details	In total 42 patients with diagnose of PsA, presence of chronic (duration ≥3 months) back pain,BASDAI value of ≥4 and back pain score (BASDAI Question 2) of ≥4, presence of active inflammation of sreening MRI...were screened, 16 patients were failed screening and 26 patients received the baseline visit.
Period 1
Period 1 title	double-blind period (overall period)
Is this the baseline period?	Yes
Allocation method	Randomised - controlled
Blinding used	Double blind
Roles blinded	Investigator, Monitor, Data analyst, Carer, Subject
Arms
Are arms mutually exclusive	No
Arm title	Tofacitinib 5mg
Arm description	-
Arm type	Experimental
Investigational medicinal product name	Tofacitinib
Investigational medicinal product code	SUB33105
Other name	XELJANZ, TOFACITINIB CITRATE
Pharmaceutical forms	Tablet
Routes of administration	Oral use
Dosage and administration details	5mg orally twice daily for a 12-week period. After week 12 began the open label period, patients were to receive Tofacitinib 5mg orally twice daily for another 12 weeks.
Arm title	Placebo 12 weeks
Arm description	-
Arm type	Placebo
Investigational medicinal product name	Placebo
Investigational medicinal product code
Other name
Pharmaceutical forms	Tablet
Routes of administration	Oral use
Dosage and administration details	Patients received Placebo orally twice daily for a 12-week period.
Number of subjects in period 1 Tofacitinib 5mg Placebo 12 weeks Started 14 12 Completed 14 12

Subject disposition Top of page

Baseline characteristics Top of page
Baseline characteristics reporting groups
Reporting group title	Tofacitinib 5mg
Reporting group description	-
Reporting group title	Placebo 12 weeks
Reporting group description	-
Reporting group values Tofacitinib 5mg Placebo 12 weeks Total Number of subjects 14 12 Age categorical Units: Subjects Age continuous Units: years     arithmetic mean (full range (min-max)) 40 (19 to 54) 41 (19 to 63) - Gender categorical Units: Subjects     Female 6 4 10     Male 8 8 16 Symptom duration (back pain) Units: years     arithmetic mean (full range (min-max)) 8 (1 to 27) 10 (1 to 22) - Duration since Diagnosis Units: years     arithmetic mean (standard deviation) 3.17 ( 3.72 ) 3.05 ( 2.27 ) - Body weight Units: kg     arithmetic mean (full range (min-max)) 78 (58 to 97) 91 (63 to 116) - Number of swollen joints Units: number     arithmetic mean (standard deviation) 3 ( 5.57 ) 1.92 ( 3.32 ) - BASMI (0-10) Bath Ankylosing Spondylitis Metrology Index -Improvement of axial mobility Units: score     arithmetic mean (standard deviation) 3.14 ( 1.02 ) 3.23 ( 1.18 ) - BASDAI BASDAI= Bath Ankylosing Spondylitis Disease Activity Index; Units: Score     arithmetic mean (standard deviation) 6.1 ( 1.39 ) 6.25 ( 1.35 ) - BASFI BASFI= Bath Ankylosing Spondylitis Disease Functional Index Units: score     arithmetic mean (standard deviation) 5.34 ( 1.51 ) 4.92 ( 1.7 ) - PASI PASI = Psoriasis Area Severity Index Units: Score     arithmetic mean (standard deviation) 4 ( 6.3 ) 3.1 ( 4 ) - HAQ-DI HAQ-DI= Health Assessment Questionnaire Disability Index Units: score     arithmetic mean (standard deviation) 1.15 ( 0.39 ) 1.01 ( 0.41 ) - CRP CRP= C-reactive protein (reference range < 5mg/L) Units: mg/l     arithmetic mean (standard deviation) 14 ( 25 ) 9 ( 8 ) - MASES Maastricht Ankylosing Spondylitis Enthesitis Score =MASES Units: Score     arithmetic mean (standard deviation) 1.64 ( 2.17 ) 3.33 ( 3.34 ) - Physician Global physician global assessment on the NRS Units: score     arithmetic mean (standard deviation) 6.21 ( 2.49 ) 5.75 ( 1.71 ) -

Baseline characteristics Top of page

End points Top of page
End points reporting groups
Reporting group title	Tofacitinib 5mg
Reporting group description	-
Reporting group title	Placebo 12 weeks
Reporting group description	-

End points Top of page

Primary: change Berlin MRI score for spine Top of page
End point title	change Berlin MRI score for spine [1]
End point description	Efficacy of the therapy in reducing inflammation in spine on MRI in patients with active axial PsA was to be assessed byBerlin MRI scoring method (range for osteitis 0-69 for the spine).
End point type	Primary
End point timeframe	at week 12 as compared to baseline
Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: In order to demonstrate a significant difference between Tofacitinib and placebo groups using the two-sided T-Test for mean difference with the power of 80% and alpha=0.05 (anticipated standard deviation = 3.0), at least 74 patients (37 per arm) should be included in the analysis set. In this trial only 26 patients were included. No statistical analysis were performed.
End point values Tofacitinib 5mg Placebo 12 weeks Number of subjects analysed 14 12 Units: score arithmetic mean (standard deviation)     baseline 4.6 ( 8.3 ) 2.9 ( 6.2 )     12 weeks 1.6 ( 3.6 ) 2.6 ( 6.2 )
No statistical analyses for this end point

Primary: change Berlin MRI score for spine Top of page

Primary: change Berlin MRI score for sacroiliac joint (SIJ) Top of page
End point title	change Berlin MRI score for sacroiliac joint (SIJ) [2]
End point description
End point type	Primary
End point timeframe	compared to baseline after 12 weeks of therapy with Tofacitinib or Placebo
Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: In order to demonstrate a significant difference between Tofacitinib and placebo groups using the two-sided T-Test for mean difference with the power of 80% and alpha=0.05 (anticipated standard deviation = 3.0), at least 74 patients (37 per arm) should be included in the analysis set. In this trial only 26 patients were included. No statistical analysis were performed.
End point values Tofacitinib 5mg Placebo 12 weeks Number of subjects analysed 14 12 Units: Score arithmetic mean (standard deviation)     baseline 3.3 ( 4.2 ) 5.5 ( 4.8 )     12 weeks 1.8 ( 3.1 ) 4.5 ( 4.7 )
No statistical analyses for this end point

Primary: change Berlin MRI score for sacroiliac joint (SIJ) Top of page

Adverse events Top of page
Adverse events information
Timeframe for reporting adverse events	overall trial
Assessment type	Systematic
Dictionary used for adverse event reporting
Dictionary name	MedDRA
Dictionary version	21.0
Reporting groups
Reporting group title	Placebo to Tofacitinib
Reporting group description	-
Reporting group title	Tofacitinib
Reporting group description	-
Serious adverse events Placebo to Tofacitinib Tofacitinib Total subjects affected by serious adverse events      subjects affected / exposed 2 / 12 (16.67%) 0 / 14 (0.00%)      number of deaths (all causes) 0 0      number of deaths resulting from adverse events 0 0 Musculoskeletal and connective tissue disorders Polyarthralgia      subjects affected / exposed 1 / 12 (8.33%) 0 / 14 (0.00%)      occurrences causally related to treatment / all 1 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Infections and infestations pneumonia associated to COVID-19      subjects affected / exposed 1 / 12 (8.33%) 0 / 14 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0
Frequency threshold for reporting non-serious adverse events: 1%
Non-serious adverse events Placebo to Tofacitinib Tofacitinib Total subjects affected by non serious adverse events      subjects affected / exposed 12 / 12 (100.00%) 10 / 14 (71.43%) Investigations Transaminases increased      subjects affected / exposed 2 / 12 (16.67%) 2 / 14 (14.29%)      occurrences all number 2 2 Injury, poisoning and procedural complications Traumatic chest injury NOS      subjects affected / exposed 0 / 12 (0.00%) 1 / 14 (7.14%)      occurrences all number 0 1 Vaccination adverse reaction      subjects affected / exposed 1 / 12 (8.33%) 0 / 14 (0.00%)      occurrences all number 1 0 Vascular disorders Hypertensive crisis      subjects affected / exposed 0 / 12 (0.00%) 1 / 14 (7.14%)      occurrences all number 0 1 Surgical and medical procedures Tooth extraction      subjects affected / exposed 1 / 12 (8.33%) 0 / 14 (0.00%)      occurrences all number 1 0 Nervous system disorders Migraine      subjects affected / exposed 1 / 12 (8.33%) 0 / 14 (0.00%)      occurrences all number 1 0 Headache      subjects affected / exposed 0 / 12 (0.00%) 1 / 14 (7.14%)      occurrences all number 0 1 Concentration impaired      subjects affected / exposed 0 / 12 (0.00%) 1 / 14 (7.14%)      occurrences all number 0 1 General disorders and administration site conditions flu-like symptoms      subjects affected / exposed 3 / 12 (25.00%) 0 / 14 (0.00%)      occurrences all number 4 0 Malaise      subjects affected / exposed 0 / 12 (0.00%) 1 / 14 (7.14%)      occurrences all number 0 1 Pain      subjects affected / exposed 0 / 12 (0.00%) 1 / 14 (7.14%)      occurrences all number 0 1 Gastrointestinal disorders Diarrhea      subjects affected / exposed 2 / 12 (16.67%) 0 / 14 (0.00%)      occurrences all number 2 0 Gastroenteritis/ Gastritis      subjects affected / exposed 0 / 12 (0.00%) 2 / 14 (14.29%)      occurrences all number 0 2 Food poisoning      subjects affected / exposed 0 / 12 (0.00%) 1 / 14 (7.14%)      occurrences all number 0 1 Nausea      subjects affected / exposed 1 / 12 (8.33%) 0 / 14 (0.00%)      occurrences all number 2 0 Reproductive system and breast disorders Prostatitis      subjects affected / exposed 1 / 12 (8.33%) 0 / 14 (0.00%)      occurrences all number 1 0 Respiratory, thoracic and mediastinal disorders Dry cough      subjects affected / exposed 1 / 12 (8.33%) 0 / 14 (0.00%)      occurrences all number 1 0 Musculoskeletal and connective tissue disorders Degeneration of cervical intervertebral disc      subjects affected / exposed 1 / 12 (8.33%) 0 / 14 (0.00%)      occurrences all number 1 0 Psoriatic spondylitis      subjects affected / exposed 1 / 12 (8.33%) 1 / 14 (7.14%)      occurrences all number 1 1 Metatarsalgia      subjects affected / exposed 0 / 12 (0.00%) 1 / 14 (7.14%)      occurrences all number 0 1 Infections and infestations Upper respiratory infection (Covid-19)      subjects affected / exposed 2 / 12 (16.67%) 1 / 14 (7.14%)      occurrences all number 2 2 Bronchitis      subjects affected / exposed 1 / 12 (8.33%) 0 / 14 (0.00%)      occurrences all number 1 0 chronic sinusitis      subjects affected / exposed 1 / 12 (8.33%) 0 / 14 (0.00%)      occurrences all number 1 0 Herpes labialis      subjects affected / exposed 0 / 12 (0.00%) 1 / 14 (7.14%)      occurrences all number 0 1 Abscess jaw      subjects affected / exposed 0 / 12 (0.00%) 1 / 14 (7.14%)      occurrences all number 0 1

Adverse events Top of page

More information Top of page
Substantial protocol amendments (globally)
Were there any global substantial amendments to the protocol? Yes
Date	Amendment
26 Mar 2020	Update protocol version 2.1 from 09/03/2020- (update IB to SmPc Xeljanz film-coated tablets, adjustment of inclusion criteria: Age limit <65 years, and selection of patients based on number, age, gender)
20 Oct 2021	Update protocol version 3.0 dated 14/10/2021 (update IB to SmPc Tofacitinal and change ICF)
Interruptions (globally)
Were there any global interruptions to the trial? No
Limitations and caveats
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
Only 26 of the originally 80 planned patients were included. The reason for this was the black box warning for tofacitinib not to be used as first-line therapy in patients with cardiovascular risk and the COVID-19 pandemic time.

More information Top of page