Download PDF

Clinical Trial Results:
Randomised Control Trial of the Clinical Effectiveness, Safety and Cost Effectiveness of Adalimumab in Combination with Methotrexate for the Treatment of Juvenile Idiopathic Arthritis Associated Uveitis.

Summary
EudraCT number	2010-021141-41
Trial protocol	GB
Global end of trial date	14 Dec 2016

Results information
Results version number	v2(current)
This version publication date	04 May 2019
First version publication date	23 Mar 2018
Other versions	v1
Version creation reason	Changes to summary attachments During site closedown for the trial, data were identified for participants that had not been sent to CTRC by sites and subsequently were not present in the database at the time of data lock. The impact was assessed by the statistics team who confirmed the omitted data would have minimal impact on the trial results so therefore the database was not unlocked. This event was not considered a serious breach. Full details are described within the attached file note. The report has not changed.
Summary report(s)	Baseline Data Supplementary Material - Open Label Phase Results File note

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

CH/2008/3061

ISRCTN number

ISRCTN10065623

US NCT number

WHO universal trial number (UTN)

Other trial identifiers

Funding reference numbers: HTA 90/51/01; ARUK 19612

Sponsor organisation name

University Hospitals Bristol NHS Foundation Trust

Sponsor organisation address

UH Bristol Education Centre, Level 3, Upper Maudlin Street, Bristol, United Kingdom, BS2 8AE

Public contact

Ashley Jones, Clinical Trials Research Centre, University of Liverpool, +44 151 795 8751, ctrcqa@liverpool.ac.uk

Scientific contact

Ashley Jones, Clinical Trials Research Centre, University of Liverpool, +44 151 795 8751, ctrcqa@liverpool.ac.uk

Is trial part of an agreed paediatric investigation plan (PIP)

Yes

EMA paediatric investigation plan number(s)

EMEA-000366-PIP12-02

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

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

Yes

Analysis stage

Final

Date of interim/final analysis

02 Aug 2017

Is this the analysis of the primary completion data?

Yes

Primary completion date

16 Jun 2015

Global end of trial reached?

Yes

Global end of trial date

14 Dec 2016

Was the trial ended prematurely?

Main objective of the trial

To compare how effective the use of adalimumab, in combination with methotrexate versus methotrexate alone with regard to controlling disease activity in refractory uveitis associated with juvenile idiopathic arthritis. Please note: As stated in the protocol, the formal end of trial is defined as the date of final database lock which was on 02/08/17.

Protection of trial subjects

The first dose of IMP was administered by the research / clinical team looking after the patient. All participants or a family member were invited to self-administer the study treatment after the first dose and taught as such to do this under procedures in place within each participating centre for teaching this. The first dose they administered was also be under supervision of the clinical team, who ensured they are confident and able to carry out all parts of the procedure appropriately and accurately. This would allow patients to then have their remaining trial treatment in the familiar surroundings of their home to reduce distress. If they did not want to do this, then arrangements were put in place on an individual basis for ensuring trial medication is administered as prescribed. Study visits and study assessments were set around routine clinical care to minimise the inconvenience for patients and families, travel expenses were provided for visits outside of routine care that were specific for SYCAMORE.

Background therapy

All subjects to receive a stable dose of methotrexate

Evidence for comparator

Methotrexate (MTX) is well established as the first-line disease modifying agent in the management of JIA. MTX is also thought to be effective for JIA-associated uveitis in children with moderate-to-severe uveitis, but there have been no prospective randomised placebo-controlled trials of MTX or steroid regimens in JIA-associated uveitis. Adalimumab is a fully human monoclonal antibody engineered by gene technology that uses site-directed mutagenesis to enhance its binding efficiency to tumor necrosis factor (TNF). It does not contain nonhuman or artificial protein sequences. There are no prospective studies of efficacy and safety of anti-TNF agents in JIA-associated uveitis. In the randomised controlled trial of adalimumab in JIA that demonstrated safety and efficacy, the most commonly reported adverse events were infections and injection-site reactions. Serious adverse events considered possibly related to study drug by the investigator occurred in 14 patients.

Actual start date of recruitment

21 Oct 2011

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United Kingdom: 90

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

The trial took place in 17 United Kingdom centres; 14 of these centres randomised at least one participant. The first patient was randomised on the 27th October 2011 and the last patient was randomised on the 31st March 2015.

Screening details

There was a total of 332 patients assessed for eligibility from 519 screenings (patients could be screened on multiple occasions). 130 (39%) were eligible and 90 were consented and were randomised.

Number of subjects started

Number of subjects completed

Period 1 title

Blinded Phase

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Carer, Assessor

Blinding implementation details

This trial was placebo-controlled and all study assessments were carried out by health professionals, parents/carers and patients without knowledge of treatment allocation. The placebo solution for the injection was a clear, colourless solution presented in a single-use vial for the injection in volumes of 0.8mL. The packaging of the kit of adalimumab and placebo were identical. Each kit consisted of two vials of adalimumab or placebo in an outer carton.

Are arms mutually exclusive

Yes

Adalimumab (blinded phase)

Arm description

Adalimumab subcutaneous injection every 2 weeks for 18 months. Participants in the adalimumab group who were still on treatment at the point of the TSC decision to unblind subsequently took part in an open-label phase of the trial. Placebo participants moved straight to follow-up. See attached summary for the results of any analyses including the open-label phase data.

Arm type

Experimental

Investigational medicinal product name

Adalimumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

20mg for participants weighing <30kg; 40mg for participants weighing ≥ 30kg

Placebo (blinded phase)

Arm description

Placebo subcutaneous injection every 2 weeks for 18 months

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Placebo subcutaneous injection every 2 weeks for 18 months

Number of subjects in period 1	Adalimumab (blinded phase)	Placebo (blinded phase)
Started	60	30
Completed	58	29
Not completed	2	1
Consent withdrawn by subject	2	1

Period 2 title

Follow-up

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Adalimumab (follow-up)

Arm description

The original trial design included an 18 month treatment period followed by an 18 month follow-up period. If the patient was deemed to be classified as a treatment failure or discontinued their allocated treatment (either before or at 18 months) they were to enter into the follow-up period of the trial. During this follow-up period, patients were to be assessed at 3, 6, 9, 12, 15 and 18 months post treatment cessation. A later change to the study protocol (see More Information: Substantial Protocol Amendments section) allowed the follow-up period to be reduced from 18 months to 6 months. The assessments were then carried out at two follow-up visits at 3 months and 6 months post treatment cessation.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Placebo (follow-up)

Arm description

See above.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Number of subjects in period 2	Adalimumab (follow-up)	Placebo (follow-up)
Started	58	29
Completed	58	29

Baseline characteristics

Top of page

Reporting group title

Adalimumab (blinded phase)

Reporting group description

Reporting group title

Placebo (blinded phase)

Reporting group description

Placebo subcutaneous injection every 2 weeks for 18 months

Reporting group values	Adalimumab (blinded phase)	Placebo (blinded phase)	Total
Number of subjects	60	30	90
Age categorical
Units: Subjects
In utero	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0
Newborns (0-27 days)	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0
Children (2-11 years)	46	23	69
Adolescents (12-17 years)	14	7	21
Adults (18-64 years)	0	0	0
From 65-84 years	0	0	0
85 years and over	0	0	0
Age continuous
Age at randomisation
Units: years
arithmetic mean (standard deviation)	9.07 ( 3.94 )	8.56 ( 3.79 )	-
Gender categorical
Gender
Units: Subjects
Female	47	23	70
Male	13	7	20
Number of study eyes
Units: Subjects
Unilateral	43	22	65
Bilateral	17	8	25
Weight (kg)
Units: Subjects
<30kg	33	17	50
>=30kg	26	13	39
Unobtainable	1	0	1
Type of JIA (Internation League of Associations for Rheumatology (ILAR) classification)
Units: Subjects
Extended oligoarthritis	14	7	21
Persistent oligoarthritis	36	17	53
Polyarthritis RF negative	8	4	12
Polyarthritis RF positive	1	1	2
Psoriatic arthritis	1	1	2
Anti-nuclear antibody
Units: Subjects
Negative	24	10	34
Positive	33	15	48
Not carried out	3	5	8
Double-stranded deoxyribonucleic acid
Units: Subjects
Negative	47	22	69
Positive	3	2	5
Not carried out	10	6	16
Rheumatoid factor
Units: Subjects
Negative	46	20	66
Positive	1	3	4
Not carried out	13	7	20
Disease duration
6 adalimumab and 4 placebo participants had unobtainable disease duration.
Units: years
arithmetic mean (standard deviation)	5.58 ( 3.69 )	4.81 ( 3.19 )	-
Physician global assessment of disease activity
2 adalimumab and 1 placebo participants had unobtainable physician global assessment of disease activity.
Units: Physician global assessment
arithmetic mean (standard deviation)	0.76 ( 1.48 )	0.83 ( 1.09 )	-
Active joint count [all joints]
Units: Active joints
arithmetic mean (standard deviation)	0.57 ( 2.03 )	1.1 ( 2.23 )	-
Swollen joint count [all joints]
Units: Swollen joints
arithmetic mean (standard deviation)	0.55 ( 1.66 )	1 ( 1.55 )	-

End points

Top of page

Reporting group title

Adalimumab (blinded phase)

Reporting group description

Reporting group title

Placebo (blinded phase)

Reporting group description

Placebo subcutaneous injection every 2 weeks for 18 months

Reporting group title

Adalimumab (follow-up)

Reporting group description

Reporting group title

Placebo (follow-up)

Reporting group description

See above.

Primary: Blinded Phase: Time to treatment failure

Top of page

End point title

Blinded Phase: Time to treatment failure

End point description

Treatment failure was classified as occurrence of one of the following: 1) Anterior segment inflammatory score grade (SUN criteria) following at least 3 months of therapy. 2) Use of Concomitant Medications: At any time, requirement to use concomitant medications in manner out with pre-defined acceptable criteria, or any of the concomitant medications not allowed. 3) Intermittent or continuous suspension of study treatment (adalimumab/placebo) for a cumulative period longer than 4 weeks Full details on the treatment failure criteria can be found within the protocol.

End point type

Primary

End point timeframe

Participants were assessed for treatment failure from randomisation up until: -time of treatment failure -completion of 18 months of treatment -unblinding following TSC decision, whichever occurred first.

End point values	Adalimumab (blinded phase)	Placebo (blinded phase)
Number of subjects analysed	60	30
Units: Treatment Failures
Failed treatment	14	17
Censored	46	13

Attachments

Untitled (Filename: Blinded Phase - Primary Outcome.pdf)

Time to treatment failure

Comparison groups

Placebo (blinded phase) v Adalimumab (blinded phase)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Logrank

Parameter type

Cox proportional hazard

Point estimate

0.25

Confidence interval

level

95%

sides

2-sided

lower limit

0.12

upper limit

0.51

Secondary: Blinded phase: Number of participants failing treatment

Top of page

End point title

Blinded phase: Number of participants failing treatment

End point description

End point type

Secondary

End point timeframe

End point values	Adalimumab (blinded phase)	Placebo (blinded phase)
Number of subjects analysed	60	30
Units: Treatment Failures
Failed treatment	14	17
Did not fail treatment	46	13

Number of participants failing treatment

Comparison groups

Placebo (blinded phase) v Adalimumab (blinded phase)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002

Method

Chi-squared

Parameter type

Risk ratio (RR)

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

0.23

upper limit

0.72

Secondary: Blinded phase: Total oral corticosteroid dose

Top of page

End point title

Blinded phase: Total oral corticosteroid dose

End point description

The total dose is calculated by summing the daily doses and standardised to per patient years.

End point type

Secondary

End point timeframe

Participants are assessed from randomisation until: -time of treatment failure -completion of 18 months of treatment -unblinding following TSC decision, whichever occurred first.

End point values	Adalimumab (blinded phase)	Placebo (blinded phase)
Number of subjects analysed	5 ^[1]	1 ^[2]
Units: miligrams per patient year
number (not applicable)
Total dose per patient years	804.31	3767.74

Notes
[1] - 5 participants were taking oral corticosteroids at randomisation.
[2] - 1 participant was taking oral corticosteroids at randomisation.

Total oral corticosteroid dose

Comparison groups

Adalimumab (blinded phase) v Placebo (blinded phase)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Poisson regression

Parameter type

Rate ratio

Point estimate

0.21

Confidence interval

level

95%

sides

2-sided

lower limit

0.2

upper limit

0.23

Secondary: Blinded phase: Reduction in systemic corticosteroid dose from entry dose to 0mg

Top of page

End point title

Blinded phase: Reduction in systemic corticosteroid dose from entry dose to 0mg

End point description

Reduction in systemic corticosteroid dose from entry dose to 0mg will be analysed for a subset of patients, as not everyone will be taking systemic corticosteroids at randomisation. The planned analysis was a competing risks time-to-event model. No comparative analysis was able to be performed due to the fact that statistical algorithm did not converge.

End point type

Secondary

End point timeframe

Participants were assessed from randomisation up until: -time of treatment failure -completion of 18 months of treatment -unblinding following TSC decision, whichever occurred first.

End point values	Adalimumab (blinded phase)	Placebo (blinded phase)
Number of subjects analysed	5 ^[3]	1 ^[4]
Units: Events
Reduced dose	3	1
Censored	2	0

Notes
[3] - 5 participants were prescribed systemic corticosteroids >0mg at baseline.
[4] - 1 participant was prescribed systemic corticosteroids >0mg at baseline.

No statistical analyses for this end point

Secondary: Blinded phase: Rate of systemic corticosteroid dose from entry dose

Top of page

End point title

Blinded phase: Rate of systemic corticosteroid dose from entry dose

End point description

The total dose is calculated by summing the daily doses and standardised to per patient years.

End point type

Secondary

End point timeframe

Participants were assessed from randomisation up until: -time of treatment failure -completion of 18 months of treatment -unblinding following TSC decision, whichever occurred first.

End point values	Adalimumab (blinded phase)	Placebo (blinded phase)
Number of subjects analysed	5 ^[5]	1 ^[6]
Units: miligrams per patient years
number (not applicable)
Total dose per patient years	804.31	3767.74

Notes
[5] - 5 participants were taking systemic corticosteroids at randomisation.
[6] - 1 participant was taking systemic corticosteroids at randomisation.

Rate of systemic corticosteroids from entry dose

Comparison groups

Placebo (blinded phase) v Adalimumab (blinded phase)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Poisson regression

Parameter type

Rate ratio

Point estimate

0.21

Confidence interval

level

95%

sides

2-sided

lower limit

0.2

upper limit

0.23

Secondary: Blinded phase: Time to reduction to <2 drops in topical corticosteroids

Top of page

End point title

Blinded phase: Time to reduction to <2 drops in topical corticosteroids

End point description

Time to reduction to < 2 drops for those patients already on >= 2 drops at randomisation.

End point type

Secondary

End point timeframe

Participants were assessed from randomisation up until: -time of treatment failure -completion of 18 months of treatment -unblinding following TSC decision, whichever occurred first.

End point values	Adalimumab (blinded phase)	Placebo (blinded phase)
Number of subjects analysed	45 ^[7]	18 ^[8]
Units: Events
Reduced drops	24	3
Censored	21	15

Notes
[7] - 45 participants were on ≥ 2 drops per day at baseline.
[8] - 18 participants were on ≥ 2 drops per day at baseline.

Time to reduction to <2 drops

Statistical analysis description

This was a competing risks analysis, accounting for the time to treatment failure.

Comparison groups

Placebo (blinded phase) v Adalimumab (blinded phase)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.03

Method

Fine and Gray

Parameter type

Hazard ratio (HR)

Point estimate

3.99

Confidence interval

level

95%

sides

2-sided

lower limit

1.18

upper limit

25.2

Secondary: Blinded phase: Need for pulsed corticosteroid

Top of page

End point title

Blinded phase: Need for pulsed corticosteroid

End point description

Need for pulsed corticosteroid.

End point type

Secondary

End point timeframe

Participants were assessed from randomisation up until: -time of treatment failure -completion of 18 months of treatment -unblinding following TSC decision, whichever occurred first.

End point values	Adalimumab (blinded phase)	Placebo (blinded phase)
Number of subjects analysed	60	30
Units: Events
Needed pulsed corticosteroids	2	1
Did not need pulsed corticosteroids	58	29

Need for pulsed corticosteroid

Comparison groups

Adalimumab (blinded phase) v Placebo (blinded phase)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

> 0.99

Method

Fisher exact

Parameter type

Risk ratio (RR)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.09

upper limit

10.59

Secondary: Blinded phase: Optic and Ocular: Number of participants with disease flares following a minimum of 3 months of disease control

Top of page

End point title

Blinded phase: Optic and Ocular: Number of participants with disease flares following a minimum of 3 months of disease control

End point description

Disease control is when a patient has a score of “0” for the field “AC cells (SUN)” for 3 months (12 weeks ± 7 days i.e. at least 11 weeks) from randomisation within each eligible eye and has had at least one topical treatment during this time. Disease flares are defined as an increase in the “AC cells (SUN)” score at two consecutive visits at least 4 weeks apart. Two analyses were performed for this outcome: 3 months disease control and a flare in at least one eye, and 3 months disease control in both eyes and a flare in at least one eye. The latter has been uploaded as a supplementary file.

End point type

Secondary

End point timeframe

Participants were assessed from randomisation up until: -time of treatment failure -completion of 18 months of treatment -unblinding following TSC decision, whichever occurred first.

End point values	Adalimumab (blinded phase)	Placebo (blinded phase)
Number of subjects analysed	60	30
Units: Events
Disease flare	5	1
No disease flare	55	29

Disease flares following 3 months disease control

Comparison groups

Adalimumab (blinded phase) v Placebo (blinded phase)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.66

Method

Fisher exact

Parameter type

Risk ratio (RR)

Point estimate

2.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.31

upper limit

20.45

Secondary: Blinded phase: Optic and Ocular: Number of participants with disease flares within the first 3 months of the study

Top of page

End point title

Blinded phase: Optic and Ocular: Number of participants with disease flares within the first 3 months of the study

End point description

Disease flare is defined by worsening based on SUN criteria. Two analyses were due to be performed for this outcome: disease flare in at least one eye, and disease flare in both eyes. No participants who had a flare were eligible on both eyes and therefore the second analysis was not possible.

End point type

Secondary

End point timeframe

Participants were assessed from randomisation up until: -time of treatment failure -completion of 18 months of treatment -unblinding following TSC decision, whichever occurred first.

End point values	Adalimumab (blinded phase)	Placebo (blinded phase)
Number of subjects analysed	60	30
Units: Events
Disease flare	0	3
No disease flare	60	27

Disease flare within first 3 months

Comparison groups

Adalimumab (blinded phase) v Placebo (blinded phase)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.03

Method

Fisher exact

Parameter type

Risk ratio (RR)

Point estimate

0.07

Confidence interval

level

95%

sides

2-sided

lower limit

0.004

upper limit

1.36

Secondary: Blinded phase: Optic and Ocular: Visual acuity as measured by age-appropriate LogMAR assessment

Top of page

End point title

Blinded phase: Optic and Ocular: Visual acuity as measured by age-appropriate LogMAR assessment

End point description

Change in assessment over time. Summary tables showing the number of assessments at each time point have been uploaded as a supplementary file.

End point type

Secondary

End point timeframe

Participants were assessed from randomisation up until: -time of treatment failure -completion of 18 months of treatment -unblinding following TSC decision, whichever occurred first.

End point values	Adalimumab (blinded phase)	Placebo (blinded phase)
Number of subjects analysed	60	30
Units: LogMAR
arithmetic mean (standard deviation)
Best-case: Baseline	0.04 ( 0.15 )	0.06 ( 0.12 )
Best-case: 1 month	0.03 ( 0.17 )	0.02 ( 0.16 )
Best-case: 2 months	0.02 ( 0.17 )	0.05 ( 0.18 )
Best-case: 3 months	0.00 ( 0.16 )	0.01 ( 0.11 )
Best-case: 6 months	0.02 ( 0.20 )	0.05 ( 0.16 )
Best-case: 9 months	-0.01 ( 0.14 )	0.00 ( 0.17 )
Best-case: 12 months	-0.01 ( 0.14 )	0.03 ( 0.14 )
Best-case: 15 months	0.00 ( 0.14 )	0.00 ( 0.26 )
Best-case: 18 months	0.02 ( 0.13 )	0.02 ( 0.21 )
Worst-case: Baseline	0.05 ( 0.16 )	0.08 ( 0.12 )
Worst-case: 1 month	0.04 ( 0.18 )	0.06 ( 0.17 )
Worst-case: 2 months	0.04 ( 0.19 )	0.06 ( 0.18 )
Worst-case: 3 months	0.02 ( 0.20 )	0.03 ( 0.12 )
Worst-case: 6 months	0.03 ( 0.20 )	0.07 ( 0.19 )
Worst-case: 9 months	-0.01 ( 0.14 )	0.04 ( 0.20 )
Worst-case: 12 months	0.00 ( 0.14 )	0.08 ( 0.17 )
Worst-case: 15 months	0.00 ( 0.13 )	0.00 ( 0.26 )
Worst-case: 18 months	0.04 ( 0.11 )	0.02 ( 0.21 )

Attachments

Untitled (Filename: Blinded Phase - LogMAR.pdf)

Joint Modelling for LogMAR (best-case)

Statistical analysis description

Joint modelling of LogMAR estimating longitudinal treatment effects adjusted for dropout due to treatment failure. In this analysis, when only one eye was involved the single LogMAR value was used. When there were two eyes involved, the best LogMAR measurement was used (the minimum of the 2 values).

Comparison groups

Adalimumab (blinded phase) v Placebo (blinded phase)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.51

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.07

upper limit

0.02

Joint Modelling for LogMAR (worst-case)

Statistical analysis description

Joint modelling of LogMAR estimating longitudinal treatment effects adjusted for dropout due to treatment failure. In this analysis, when only one eye was involved the single LogMAR value was used. When there were two eyes involved, the worst LogMAR measurement was used (the maximum of the 2 values).

Comparison groups

Adalimumab (blinded phase) v Placebo (blinded phase)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.36

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.07

upper limit

0.02

Secondary: Blinded phase: Optic and Ocular: Number of participants with resolution of associated optic nerve

Top of page

End point title

Blinded phase: Optic and Ocular: Number of participants with resolution of associated optic nerve

End point description

Assessed by slit lamp biomicroscopy or optical coherence tomography (OCT) where available. Two analyses were due to be performed for this outcome: resolution in at least 1 eye, and resolution in both eyes. There were no participants who had associated optic nerve at baseline or developed this during the course of the study in the placebo group. It was, therefore, not possible to carry out either of the planned statistical tests of these data.

End point type

Secondary

End point timeframe

Participants were assessed from randomisation up until: -time of treatment failure -completion of 18 months of treatment -unblinding following TSC decision, whichever occurred first.

End point values	Adalimumab (blinded phase)	Placebo (blinded phase)
Number of subjects analysed	4 ^[9]	0 ^[10]
Units: Events
Resolved	2
Not resolved	2

Notes
[9] - There were 4 participants who had associated optic nerve at baseline or developed it later.
[10] - There were 0 participants who had associated optic nerve at baseline or developed it later.

No statistical analyses for this end point

Secondary: Blinded phase: Optic and Ocular: Number of participants with resolution of macular oedema

Top of page

End point title

Blinded phase: Optic and Ocular: Number of participants with resolution of macular oedema

End point description

Assessed by slit lamp biomicroscopy or optical coherence tomography (OCT) where available. Two analyses were performed for this outcome: resolution in at least 1 eye, and resolution in both eyes. The latter has been uploaded as a supplementary file.

End point type

Secondary

End point timeframe

End point values	Adalimumab (blinded phase)	Placebo (blinded phase)
Number of subjects analysed	4 ^[11]	2 ^[12]
Units: Events
Resolved	3	0
Not resolved	1	2

Attachments

Untitled (Filename: Blinded Phase - Macular Oedema.pdf)

Notes
[11] - There were 4 participants who had MO at baseline or developed it later.
[12] - There were 2 participants who had MO at baseline or developed it later.

Resolution of macular oedema

Comparison groups

Adalimumab (blinded phase) v Placebo (blinded phase)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4

Method

Fisher exact

Parameter type

Risk ratio (RR)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.34

upper limit

74.52

Secondary: Blinded phase: Optic and Ocular: Number of participants with disease control for 3 months

Top of page

End point title

Blinded phase: Optic and Ocular: Number of participants with disease control for 3 months

End point description

Disease control is defined as zero cells, with topical treatment for 3 months. Two analyses were performed for this outcome: disease control in at least 1 eye, and disease control in both eyes. The latter has been uploaded as a supplementary file.

End point type

Secondary

End point timeframe

End point values	Adalimumab (blinded phase)	Placebo (blinded phase)
Number of subjects analysed	60	30
Units: Events
Disease control	23	2
No disease control	37	28

Attachments

Untitled (Filename: Blinded Phase - Number of participants with disease control for 3 months.pdf)

Disease control for 3 months

Comparison groups

Adalimumab (blinded phase) v Placebo (blinded phase)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001

Method

Fisher exact

Parameter type

Risk ratio (RR)

Point estimate

5.75

Confidence interval

level

95%

sides

2-sided

lower limit

1.45

upper limit

22.78

Secondary: Blinded phase: Optic and Ocular: Number of participants with disease control for 6 months

Top of page

End point title

Blinded phase: Optic and Ocular: Number of participants with disease control for 6 months

End point description

Disease control is defined as zero cells, with topical treatment for 6 months. Two analyses were performed for this outcome: disease control in at least 1 eye, and disease control in both eyes. The latter has been uploaded as a supplementary file.

End point type

Secondary

End point timeframe

End point values	Adalimumab (blinded phase)	Placebo (blinded phase)
Number of subjects analysed	60	30
Units: Events
Disease control	17	1
No disease control	43	29

Attachments

Untitled (Filename: Blinded Phase - Number of participants with disease control for 6 months.pdf)

Disease control 6 months

Comparison groups

Adalimumab (blinded phase) v Placebo (blinded phase)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.005

Method

Fisher exact

Parameter type

Risk ratio (RR)

Point estimate

8.5

Confidence interval

level

95%

sides

2-sided

lower limit

1.19

upper limit

60.87

Secondary: Blinded phase: Optic and Ocular: Number of participants entering disease remission for 3 months

Top of page

End point title

Blinded phase: Optic and Ocular: Number of participants entering disease remission for 3 months

End point description

Disease remission is defined as zero cells without topical treatment for 3 months. Two analyses were performed for this outcome: disease remission in at least 1 eye, and disease remission in both eyes. The latter has been uploaded as a supplementary file.

End point type

Secondary

End point timeframe

End point values	Adalimumab (blinded phase)	Placebo (blinded phase)
Number of subjects analysed	60	30
Units: Events
Remission	15	1
No remission	45	29

Disease remission for 3 months

Comparison groups

Adalimumab (blinded phase) v Placebo (blinded phase)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.02

Method

Fisher exact

Parameter type

Risk ratio (RR)

Point estimate

7.5

Confidence interval

level

95%

sides

2-sided

lower limit

1.04

upper limit

54.12

Secondary: Blinded phase: Optic and Ocular: Number of participants entering disease remission for 6 months

Top of page

End point title

Blinded phase: Optic and Ocular: Number of participants entering disease remission for 6 months

End point description

Disease remission is defined as zero cells without topical treatment for 6 months. Two analyses were performed for this outcome: disease remission in at least 1 eye, and disease remission in both eyes. The latter has been uploaded as a supplementary file.

End point type

Secondary

End point timeframe

End point values	Adalimumab (blinded phase)	Placebo (blinded phase)
Number of subjects analysed	60	30
Units: Events
Remission	13	0
No remission	47	30

Attachments

Untitled (Filename: Blinded Phase - Number of participants with disease remission for 6 months.pdf)

Disease remission 6 months

Comparison groups

Adalimumab (blinded phase) v Placebo (blinded phase)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.004

Method

Fisher exact

Parameter type

Risk ratio (RR)

Point estimate

13.72

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

223.26

Secondary: Blinded phase: Optic and Ocular: Duration of sustaining inactive disease

Top of page

End point title

Blinded phase: Optic and Ocular: Duration of sustaining inactive disease

End point description

Inactive disease is defined as zero cells with or without topical treatment.

End point type

Secondary

End point timeframe

End point values	Adalimumab (blinded phase)	Placebo (blinded phase)
Number of subjects analysed	60	30
Units: Days
least squares mean (standard error)	180.91 ( 16.81 )	16.36 ( 23.79 )

Duration of inactive disease

Comparison groups

Adalimumab (blinded phase) v Placebo (blinded phase)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

164.55

Confidence interval

level

95%

sides

2-sided

lower limit

104.41

upper limit

224.69

Secondary: Blinded phase: Quality of life assessments: Childhood Health Questionnaire (CHQ)

Top of page

End point title

Blinded phase: Quality of life assessments: Childhood Health Questionnaire (CHQ)

End point description

The CHQ consists of two scores: Physical score (PhS) Psychosocial score (PsS) Summary tables showing the number of assessments at each time point have been uploaded as a supplementary file.

End point type

Secondary

End point timeframe

Participants were assessed from randomisation up until: -time of treatment failure -completion of 18 months of treatment -unblinding following TSC decision, whichever occurred first.

End point values	Adalimumab (blinded phase)	Placebo (blinded phase)
Number of subjects analysed	53 ^[13]	22 ^[14]
Units: CHQ
arithmetic mean (standard deviation)
PhS: Baseline	43.20 ( 11.84 )	40.48 ( 16.36 )
PhS: 1 month	45.54 ( 11.29 )	44.73 ( 12.10 )
PhS: 2 months	47.54 ( 10.69 )	43.65 ( 15.56 )
PhS: 3 months	46.50 ( 13.13 )	47.35 ( 7.97 )
PhS: 6 months	47.16 ( 11.84 )	41.95 ( 15.79 )
PhS: 9 months	47.50 ( 11.26 )	45.20 ( 14.77 )
PhS: 12 months	47.29 ( 13.06 )	53.09 ( 4.79 )
PhS: 15 months	42.85 ( 15.88 )	55.75 ( 2.48 )
PhS: 18 months	45.92 ( 12.06 )	53.77 ( 9.71 )
PsS: Baseline	51.17 ( 9.53 )	49.48 ( 7.55 )
PsS: 1 month	51.06 ( 10.36 )	50.01 ( 10.27 )
PsS: 2 months	53.02 ( 10.00 )	50.20 ( 10.75 )
PsS: 3 months	54.12 ( 9.02 )	54.21 ( 8.57 )
PsS: 6 months	53.94 ( 9.79 )	49.68 ( 11.56 )
PsS: 9 months	55.82 ( 6.84 )	50.26 ( 13.72 )
PsS: 12 months	54.08 ( 9.22 )	54.18 ( 8.83 )
PsS: 15 months	53.56 ( 7.76 )	53.27 ( 11.83 )
PsS: 18 months	53.58 ( 11.71 )	47.25 ( 18.64 )

Attachments

Untitled (Filename: Blinded Phase - CHQ.pdf)

Notes
[13] - 53 had a baseline measurement.
[14] - 22 had a baseline assessment.

CHQ: Psychosocial subscale (PsS)

Statistical analysis description

Joint modelling for estimating longitudinal treatment effects adjusted for dropout due to treatment failure.

Comparison groups

Adalimumab (blinded phase) v Placebo (blinded phase)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.15

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

2.31

Confidence interval

level

95%

sides

2-sided

lower limit

-0.44

upper limit

5.4

CHQ: Physical subscale (PhS)

Statistical analysis description

Joint modelling for estimating longitudinal treatment effects adjusted for dropout due to treatment failure.

Comparison groups

Adalimumab (blinded phase) v Placebo (blinded phase)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.55

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

1.16

Confidence interval

level

95%

sides

2-sided

lower limit

-2.41

upper limit

5.05

Secondary: Blinded phase: Quality of life assessments: Childhood Health Assessment Questionnaire (CHAQ)

Top of page

End point title

Blinded phase: Quality of life assessments: Childhood Health Assessment Questionnaire (CHAQ)

End point description

The overall index is calculated by summing the overall scores for each of the categories in the CHAQ and dividing by the number of categories answered. This will give a score between 0 and 3. Summary tables showing the number of assessments at each time point have been uploaded as a supplementary file.

End point type

Secondary

End point timeframe

Participants were assessed from randomisation up until: -time of treatment failure -completion of 18 months of treatment -unblinding following TSC decision, whichever occurred first.

End point values	Adalimumab (blinded phase)	Placebo (blinded phase)
Number of subjects analysed	59 ^[15]	28 ^[16]
Units: CHAQ
arithmetic mean (standard deviation)
Baseline	0.52 ( 0.64 )	0.48 ( 0.49 )
1 month	0.41 ( 0.56 )	0.60 ( 0.55 )
2 months	0.38 ( 0.53 )	0.54 ( 0.59 )
3 months	0.36 ( 0.58 )	0.37 ( 0.47 )
6 months	0.36 ( 0.61 )	0.46 ( 0.63 )
9 months	0.35 ( 0.63 )	0.36 ( 0.57 )
12 months	0.33 ( 0.60 )	0.09 ( 0.15 )
15 months	0.43 ( 0.58 )	0.03 ( 0.04 )
18 months	0.30 ( 0.48 )	0.03 ( 0.05 )

Attachments

Untitled (Filename: Blinded Phase - CHAQ.pdf)

Notes
[15] - 59 had a baseline assessment.
[16] - 28 had a baseline assessment.

CHAQ

Statistical analysis description

Joint modelling for estimating longitudinal treatment effects adjusted for dropout due to treatment failure.

Comparison groups

Adalimumab (blinded phase) v Placebo (blinded phase)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.09

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.14

Confidence interval

level

95%

sides

2-sided

lower limit

-0.31

upper limit

0.02

Secondary: Blinded phase: American College of Rheaumatology (ACR) score

Top of page

End point title

Blinded phase: American College of Rheaumatology (ACR) score

End point description

The 6 paediatric core set criteria assessed at each study visit are:  Physician global assessment of disease activity (10 cm visual analogue scale).  Parent/patient assessment of overall well-being (10 cm visual analogue scale).  Functional ability (Childhood Health Assessment Questionnaire, CHAQ).  Number of joints with active arthritis.  Number of joints with limited range of movement.  Erythrocyte sedimentation rate. Summary tables showing the number of assessments at each time point have been uploaded as a supplementary file. The ACR Paediatric 30, 50, 70, 90 and 100 levels are defined as 30%, 50%, 70%, 90% and 100% improvement, respectively, in a minimum of three variables in the core set with worsening of one variable by no more than 30% as defined in the ACR criteria. The frequencies below show the number of participants who achieved each ACR level.

End point type

Secondary

End point timeframe

Participants were assessed from randomisation up until: -time of treatment failure -completion of 18 months of treatment -unblinding following TSC decision, whichever occurred first.

End point values	Adalimumab (blinded phase)	Placebo (blinded phase)
Number of subjects analysed	46 ^[17]	25 ^[18]
Units: ACR frequency
number (not applicable)
ACR30: 1 month	12	7
ACR30: 2 months	16	8
ACR30: 3 months	16	6
ACR30: 6 months	13	3
ACR30: 9 months	10	1
ACR30: 12 months	12	2
ACR30: 15 months	8	1
ACR30: 18 months	9	1
ACR50: 1 month	7	7
ACR50: 2 months	10	7
ACR50: 3 months	13	5
ACR50: 6 months	11	3
ACR50: 9 months	9	1
ACR50: 12 months	10	2
ACR50: 15 months	6	1
ACR50: 18 months	8	1
ACR70: 1 month	2	5
ACR70: 2 months	5	3
ACR70: 3 months	9	3
ACR70: 6 months	9	3
ACR70: 9 months	7	1
ACR70: 12 months	5	1
ACR70: 15 months	5	1
ACR70: 18 months	5	1
ACR90: 1 month	2	1
ACR90: 2 months	3	1
ACR90: 3 months	7	2
ACR90: 6 months	6	2
ACR90: 9 months	7	1
ACR90: 12 months	5	1
ACR90: 15 months	4	1
ACR90: 18 months	3	1
ACR100: 1 month	1	0
ACR100: 2 months	1	1
ACR100: 3 months	2	1
ACR100: 6 months	2	1
ACR100: 9 months	5	0
ACR100: 12 months	3	0
ACR100: 15 months	1	0
ACR100: 18 months	1	0

Attachments

Untitled (Filename: Blinded Phase - ACR.pdf)

Notes
[17] - There were 46 participants with a result at 1 month; see supp. tables for totals at later timepoints
[18] - There were 25 participants with a result at 1 month; see supp. tables for totals at later timepoints

ACR30

Statistical analysis description

Joint modelling for estimating longitudinal treatment effects adjusted for dropout.

Comparison groups

Adalimumab (blinded phase) v Placebo (blinded phase)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.98

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.04

Confidence interval

level

95%

sides

2-sided

lower limit

-1.37

upper limit

1.59

ACR50

Statistical analysis description

Joint modelling for estimating longitudinal treatment effects adjusted for dropout.

Comparison groups

Adalimumab (blinded phase) v Placebo (blinded phase)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.37

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.15

upper limit

0.77

ACR70

Statistical analysis description

Joint modelling for estimating longitudinal treatment effects adjusted for dropout.

Comparison groups

Adalimumab (blinded phase) v Placebo (blinded phase)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.16

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-1.08

Confidence interval

level

95%

sides

2-sided

lower limit

-2.7

upper limit

0.46

ACR90

Comparison groups

Adalimumab (blinded phase) v Placebo (blinded phase)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.72

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.33

Confidence interval

level

95%

sides

2-sided

lower limit

-2.22

upper limit

1.39

ACR100

Comparison groups

Adalimumab (blinded phase) v Placebo (blinded phase)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.65

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.32

Confidence interval

level

95%

sides

2-sided

lower limit

-1.85

upper limit

1.17

Secondary: Blinded phase: Number of participants undergoing disease flares

Top of page

End point title

Blinded phase: Number of participants undergoing disease flares

End point description

For this secondary outcome, ‘disease flare’ refers to a flare of arthritis rather than the eye. The definition of ‘disease flare’ is a worsening of 30% or more in 3 or more of the 6 variables of the JIA core set , with no more than one variable improving by 30% or more.

End point type

Secondary

End point timeframe

Participants were assessed from randomisation up until: -time of treatment failure -completion of 18 months of treatment -unblinding following TSC decision, whichever occurred first.

End point values	Adalimumab (blinded phase)	Placebo (blinded phase)
Number of subjects analysed	60	30
Units: Events
Disease flare	0	3
No disease flare	60	27

Disease flare

Comparison groups

Adalimumab (blinded phase) v Placebo (blinded phase)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.03

Method

Fisher exact

Parameter type

Risk ratio (RR)

Point estimate

0.07

Confidence interval

level

95%

sides

2-sided

lower limit

0.004

upper limit

1.36

Secondary: Blinded phase: Number of participants with minimum disease activity

Top of page

End point title

Blinded phase: Number of participants with minimum disease activity

End point description

Minimum disease activity is defined for those with Oligoarthritis and Polyarthritis.

End point type

Secondary

End point timeframe

Participants were assessed from randomisation up until: -time of treatment failure -completion of 18 months of treatment -unblinding following TSC decision, whichever occurred first.

End point values	Adalimumab (blinded phase)	Placebo (blinded phase)
Number of subjects analysed	59 ^[19]	29 ^[20]
Units: Events
Minimum disease activity	19	4
No minimum disease activity	40	25

Notes
[19] - There were 59 participants with Oligoarticular JIA or Polyarticular JIA.
[20] - There were 29 participants with Oligoarticular JIA or Polyarticular JIA.

Minimum disease activity

Comparison groups

Adalimumab (blinded phase) v Placebo (blinded phase)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.08

Method

Chi-squared

Parameter type

Risk ratio (RR)

Point estimate

2.33

Confidence interval

level

95%

sides

2-sided

lower limit

0.87

upper limit

6.24

Secondary: Blinded phase: Number of participants requiring change in biologic and/or DMARD therapy for arthritis due to failure to respond

Top of page

End point title

Blinded phase: Number of participants requiring change in biologic and/or DMARD therapy for arthritis due to failure to respond

End point description

DMARDs are disease-modifying anti-rheumatic drugs.

End point type

Secondary

End point timeframe

End point values	Adalimumab (blinded phase)	Placebo (blinded phase)
Number of subjects analysed	60	30
Units: Events
Change in therapy	2	1
No change in therapy	58	29

Number of participants requiring change in DMARDs

Comparison groups

Adalimumab (blinded phase) v Placebo (blinded phase)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.99

Method

Fisher exact

Parameter type

Risk ratio (RR)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.2

upper limit

5.09

Secondary: Blinded phase: Participants score of the Juvenile Arthritis Disease Activity Score (JADAS)

Top of page

End point title

Blinded phase: Participants score of the Juvenile Arthritis Disease Activity Score (JADAS)

End point description

The JADAS is comprised of four components: -physician global assessment of disease activity,  -parent/patient global assessment of well-being,  -active joint count, in 27, 71 or 10 joints,  -erythrocyte sedimentation rate (ESR). The JADAS is calculated as a sum of scores giving global scores of 0-57, 0-101 and 0-40 for the JADAS-27, JADAS-71 and JADAS-10 respectively. Summary tables showing the number of assessments at each time point have been uploaded as a supplementary file.

End point type

Secondary

End point timeframe

Participants were assessed from randomisation up until: -time of treatment failure -completion of 18 months of treatment -unblinding following TSC decision, whichever occurred first.

End point values	Adalimumab (blinded phase)	Placebo (blinded phase)
Number of subjects analysed	60	30
Units: JADAS
arithmetic mean (standard deviation)
JADAS10: Baseline	3.48 ( 4.20 )	4.51 ( 5.61 )
JADAS10: 1 month	2.03 ( 2.31 )	3.12 ( 3.84 )
JADAS10: 2 months	1.62 ( 2.29 )	3.72 ( 5.76 )
JADAS10: 3 months	1.54 ( 2.13 )	3.56 ( 4.64 )
JADAS10: 6 months	1.78 ( 2.44 )	3.02 ( 3.80 )
JADAS10: 9 months	1.12 ( 1.51 )	1.42 ( 1.24 )
JADAS10: 12 months	1.46 ( 2.35 )	0.20 ( 0.26 )
JADAS10: 15 months	1.07 ( 1.28 )	1.33 ( 0.97 )
JADAS10: 18 months	1.62 ( 1.94 )	1.50 ( 1.31 )
JADAS27: Baseline	3.29 ( 3.89 )	3.65 ( 4.41 )
JADAS27: 1 month	1.92 ( 1.94 )	2.59 ( 2.71 )
JADAS27: 2 months	1.62 ( 2.29 )	3.43 ( 5.40 )
JADAS27: 3 months	1.49 ( 1.97 )	3.25 ( 4.04 )
JADAS27: 6 months	1.73 ( 2.34 )	3.02 ( 3.80 )
JADAS27: 9 months	1.12 ( 1.51 )	1.42 ( 1.24 )
JADAS27: 12 months	1.46 ( 2.35 )	0.20 ( 0.26 )
JADAS27: 15 months	1.02 ( 1.24 )	1.33 ( 0.97 )
JADAS27: 18 months	1.62 ( 1.94 )	1.50 ( 1.31 )
JADAS71: Baseline	3.54 ( 4.43 )	4.24 ( 5.95 )
JADAS71: 1 month	2.03 ( 2.31 )	3.29 ( 4.38 )
JADAS71: 2 months	1.62 ( 2.29 )	3.72 ( 5.76 )
JADAS71: 3 months	1.54 ( 2.13 )	3.79 ( 5.23 )
JADAS71: 6 months	1.78 ( 2.44 )	3.02 ( 3.80 )
JADAS71: 9 months	1.12 ( 1.51 )	1.42 ( 1.24 )
JADAS71: 12 months	1.46 ( 2.35 )	0.20 ( 0.26 )
JADAS71: 15 months	1.07 ( 1.28 )	1.33 ( 0.97 )
JADAS71: 18 months	1.62 ( 1.94 )	1.50 ( 1.31 )

Attachments

Untitled (Filename: Blinded Phase - JADAS.pdf)

JADAS10

Statistical analysis description

Joint modelling for estimating longitudinal treatment effects adjusted for dropout.

Comparison groups

Adalimumab (blinded phase) v Placebo (blinded phase)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.07

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.35

Confidence interval

level

95%

sides

2-sided

lower limit

-0.78

upper limit

0.01

JADAS27

Statistical analysis description

Joint modelling for estimating longitudinal treatment effects adjusted for dropout.

Comparison groups

Adalimumab (blinded phase) v Placebo (blinded phase)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.08

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.34

Confidence interval

level

95%

sides

2-sided

lower limit

-0.76

upper limit

0.03

JADAS71

Comparison groups

Adalimumab (blinded phase) v Placebo (blinded phase)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.07

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-0.36

Confidence interval

level

95%

sides

2-sided

lower limit

-0.78

upper limit

0.004

Secondary: Blinded phase: Compliance according to participant diaries

Top of page

End point title

Blinded phase: Compliance according to participant diaries

End point description

Treatment diaries were used to estimate participant compliance by dividing the number of doses recorded as taken in the treatment diary by the expected number of doses the participant should have taken (according to the time the participant was on treatment). No formal statistical analysis was undertaken.

End point type

Secondary

End point timeframe

Participants were assessed from randomisation up until: -withdrawal -time of treatment failure -completion of 18 months of treatment -unblinding following TSC decision, whichever occurred first.

End point values	Adalimumab (blinded phase)	Placebo (blinded phase)
Number of subjects analysed	60	30
Units: percent
number (not applicable)
Compliance	84	74

No statistical analyses for this end point

Secondary: Blinded phase: Compliance according to accountability logs

Top of page

End point title

Blinded phase: Compliance according to accountability logs

End point description

Accountability logs were used to provide another estimate of adalimumab and placebo compliance by dividing the sum of the number of vials returned used and the number of missing vials, by the number of vials issued.

End point type

Secondary

End point timeframe

Participants were assessed from randomisation up until: -withdrawal -time of treatment failure -completion of 18 months of treatment -unblinding following TSC decision, whichever occurred first.

End point values	Adalimumab (blinded phase)	Placebo (blinded phase)
Number of subjects analysed	60	30
Units: percent
number (not applicable)
Compliance	94	90

No statistical analyses for this end point

Secondary: Blinded phase: Laboratory parameters

Top of page

End point title

Blinded phase: Laboratory parameters

End point description

The parameters reported on for haematological assessments are:  -Heamatocrit  -Haemoglobin  -Red blood cell count  -White blood cell count  -Neutrophils  -Lymphocytes  -Monocytes  -Basophils  -Eosinophils  -Platelet count  -Erythrocyte sedimentation rate  -Plasma viscosity (only done if ESR not available The parameters reported on for biochemical assessments are:  -C- Reactive protein (CRP)  -Urea  -Creatinine  -Sodium  -Potassium  -Calcium  -Inorganic phosphate  -Glucose  -Chloride  -Bicarbonate  -Total bilirubin  -Alanine aminotransferase (ALT)  -Aspartate aminotransferase (AST) The parameters reported on for urinalysis are:  -Protein  -Glucose  -Blood  -Leukocyte esterase  -Specific gravity  -pH Supplementary tables summarising the data have been uploaded.

End point type

Secondary

End point timeframe

Participants were assessed from randomisation up until: -time of treatment failure -completion of 18 months of treatment -unblinding following TSC decision, whichever occurred first.

End point values	Adalimumab (blinded phase)	Placebo (blinded phase)
Number of subjects analysed	60	30
Units: See supplementary tables.	60	30

Attachments

Untitled (Filename: Blinded Phase - Laboratory Parameters.pdf)

No statistical analyses for this end point

Secondary: Blinded phase: Incremental cost-effectiveness and cost utility

Top of page

End point title

Blinded phase: Incremental cost-effectiveness and cost utility

End point description

End point type

Secondary

End point timeframe

This analysis is reported separately by Health Economists at the Universtiy of Bangor. See HTA report for full details upon publication.

End point values	Adalimumab (blinded phase)	Placebo (blinded phase)
Number of subjects analysed	60	30
Units: Unit costs	60	30

No statistical analyses for this end point

Secondary: Follow-up phase: Use of corticosteroids over duration of study period (blinded, open label and follow up phase)

Top of page

End point title

Follow-up phase: Use of corticosteroids over duration of study period (blinded, open label and follow up phase)

End point description

The total dose is calculated separately for the treatment phase and follow up period, by summing the daily doses of each oral treatment on the Concomitant Medication Form taken during each period. The total dose for each time period of interest (treatment, follow up and whole trial) should be summed across each treatment arm and standardised to per patient years for that treatment. This is calculated by dividing the total oral dose in each arm by the cumulative years all patients in the corresponding arm are on treatment for.

End point type

Secondary

End point timeframe

Duration of study period (blinded, open-label and follow-up phase).

End point values	Adalimumab (follow-up)	Placebo (follow-up)
Number of subjects analysed	5 ^[21]	1 ^[22]
Units: miligrams per patient year
number (not applicable)
Total dose per patient years	790.27	3767.74

Notes
[21] - 5 participants were taking oral corticosteroids at randomisation.
[22] - 1 participant was taking oral corticosteroids at randomisation.

Total oral corticosteroid dose

Comparison groups

Adalimumab (follow-up) v Placebo (follow-up)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Poisson regression

Parameter type

Rate ratio

Point estimate

0.21

Confidence interval

level

95%

sides

2-sided

lower limit

0.19

upper limit

0.23

Secondary: Follow-up phase: Reduction in systemic corticosteroid dose from entry dose to 0mg

Top of page

End point title

Follow-up phase: Reduction in systemic corticosteroid dose from entry dose to 0mg

End point description

Reduction in systemic corticosteroid dose from entry dose to 0mg from randomisation to end of trial. It was not possible to undertake this analysis due to the fact that the statistical algorithm did not converge.

End point type

Secondary

End point timeframe

Participants were assessed from randomisation to the end of the trial.

End point values	Adalimumab (follow-up)	Placebo (follow-up)
Number of subjects analysed	5 ^[23]	1 ^[24]
Units: Events
Reduced dose	5	1
Censored	0	0

Notes
[23] - At baseline 5 participants were prescribed systemic corticosteroids >0mg.
[24] - At baseline 1 participant was prescribed systemic corticosteroids >0mg.

No statistical analyses for this end point

Secondary: Follow-up phase: Reduction in systemic corticosteroid dose from entry dose to <5mg

Top of page

End point title

Follow-up phase: Reduction in systemic corticosteroid dose from entry dose to <5mg

End point description

Reduction in systemic corticosteroid dose from entry dose to less than 5mg from randomisation to end of trial. It was not possible to undertake the analysis as the statistical algorithm did not converge.

End point type

Secondary

End point timeframe

Participants were assessed from randomisation to the end of the trial.

End point values	Adalimumab (follow-up)	Placebo (follow-up)
Number of subjects analysed	2 ^[25]	1 ^[26]
Units: Events
Reduced dose	2	1
Censored	0	0

Notes
[25] - At baseline 2 participants were prescribed systemic corticosteroids >=5mg.
[26] - At baseline 1 participant was prescribed systemic corticosteroids >=5mg.

No statistical analyses for this end point

Secondary: Follow-up phase: Time to reduction to <2 drops in topical corticosteroids

Top of page

End point title

Follow-up phase: Time to reduction to <2 drops in topical corticosteroids

End point description

See blinded phase for full description of end-point.

End point type

Secondary

End point timeframe

Participants were assessed from randomisation to the end of the trial.

End point values	Adalimumab (follow-up)	Placebo (follow-up)
Number of subjects analysed	45 ^[27]	18 ^[28]
Units: Events
Reduced drops	27	3
Censored	18	15

Notes
[27] - There were 45 participants who were on >=2 drops at baseline.
[28] - There were 18 participants who were on >=2 drops at baseline.

Time to reduction to <2 drops

Statistical analysis description

This was a competing risks analysis, accounting for the time to treatment failure.

Comparison groups

Adalimumab (follow-up) v Placebo (follow-up)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.012

Method

Fine and Gray

Parameter type

Hazard ratio (HR)

Point estimate

4.74

Confidence interval

level

95%

sides

2-sided

lower limit

1.41

upper limit

Secondary: Follow-up phase: Need for pulsed corticosteroid

Top of page

End point title

Follow-up phase: Need for pulsed corticosteroid

End point description

See blinded phase for full description of end-point.

End point type

Secondary

End point timeframe

Participants were assessed from randomisation to the end of trial.

End point values	Adalimumab (follow-up)	Placebo (follow-up)
Number of subjects analysed	58	29
Units: Events
Needed pulsed corticosteroids	4	1
Did not need pulsed corticosteroids	54	28

Need for pulsed corticosteroids

Comparison groups

Placebo (follow-up) v Adalimumab (follow-up)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.66

Method

Fisher exact

Parameter type

Risk ratio (RR)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.23

upper limit

17.12

Secondary: Follow-up phase: Laboratory parameters

Top of page

End point title

Follow-up phase: Laboratory parameters

End point description

Supplementary tables summarising the data have been uploaded.

End point type

Secondary

End point timeframe

Participants were followed up for a maximum of 18 months post treatment.

End point values	Adalimumab (follow-up)	Placebo (follow-up)
Number of subjects analysed	58	29
Units: See supplementary tables.	58	29

Attachments

Untitled (Filename: Follow-up Phase - Laboratory Parameters.pdf)

No statistical analyses for this end point

Secondary: Blinded phase: Reduction in systemic corticosteroid dose from entry dose to <5mg

Top of page

End point title

Blinded phase: Reduction in systemic corticosteroid dose from entry dose to <5mg

End point description

Reduction in systemic corticosteroid dose from entry dose to <5mg will be analysed for a subset of patients, as not everyone will be taking systemic corticosteroids at randomisation.

End point type

Secondary

End point timeframe

Participants were assessed from randomisation up until: -time of treatment failure -completion of 18 months of treatment -unblinding, whichever occurred first.

End point values	Adalimumab (blinded phase)	Placebo (blinded phase)
Number of subjects analysed	2 ^[29]	1 ^[30]
Units: Events
Reduced dose	1	1
Censored	1	0

Notes
[29] - 2 participants were prescribed systemic corticosteroids >=5mg at baseline.
[30] - 1 participant was prescribed systemic corticosteroids >=5mg at baseline.

No statistical analyses for this end point

Secondary: Follow-up phase: Rate of systemic corticosteroid dose from entry dose

Top of page

End point title

Follow-up phase: Rate of systemic corticosteroid dose from entry dose

End point description

The total dose is calculated by summing the daily doses and standardised to per patient years.

End point type

Secondary

End point timeframe

Participants were assessed from randomisation to end of trial.

End point values	Adalimumab (follow-up)	Placebo (follow-up)
Number of subjects analysed	5 ^[31]	1 ^[32]
Units: miligrams per patient year
number (not applicable)
Total dose per patient years	790.27	3767.74

Notes
[31] - 5 participants were taking oral corticosteroids at randomisation.
[32] - 1 participant was taking oral corticosteroids at randomisation.

Rate of systemic corticosteroid dose

Comparison groups

Placebo (follow-up) v Adalimumab (follow-up)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Poisson regression

Parameter type

Rate ratio

Point estimate

0.21

Confidence interval

level

95%

sides

2-sided

lower limit

0.19

upper limit

0.23

Post-hoc: Blinded phase: Time to reduction to 0 drops in topical corticosteroids

Top of page

End point title

Blinded phase: Time to reduction to 0 drops in topical corticosteroids

End point description

This outcome is the time to reduction to 0 drops for those patients already on >0 drop at randomisation.

End point type

Post-hoc

End point timeframe

End point values	Adalimumab (blinded phase)	Placebo (blinded phase)
Number of subjects analysed	49 ^[33]	25 ^[34]
Units: Events
number (not applicable)
Events	25	4
Censored	24	21

Notes
[33] - 49 participants were on >0 drops at randomisation.
[34] - 25 participants were on >0 drops at randomisation.

Time to reduction to 0 drops

Statistical analysis description

This was a competing risks analysis, accounting for the time to treatment failure.

Comparison groups

Adalimumab (blinded phase) v Placebo (blinded phase)

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.01

Method

Fine and Gray

Parameter type

Hazard ratio (HR)

Point estimate

4.02

Confidence interval

level

95%

sides

2-sided

lower limit

1.4

upper limit

11.5

Post-hoc: Follow-up phase: Time to reduction to 0 drops in topical corticosteroid

Top of page

End point title

Follow-up phase: Time to reduction to 0 drops in topical corticosteroid

End point description

This outcome is the time to reduction to 0 drops for those patients already on >0 drops at randomisation.

End point type

Post-hoc

End point timeframe

Participants were assessed from randomisation to the end of the trial.

End point values	Adalimumab (follow-up)	Placebo (follow-up)
Number of subjects analysed	49 ^[35]	25 ^[36]
Units: Events
Reduced drops	30	4
Censored	19	21

Notes
[35] - 49 participants were on >= 0 drops per day at baseline.
[36] - 25 participants were on >= 0 drops per day at baseline.

Time to reduction to 0 drops

Comparison groups

Adalimumab (follow-up) v Placebo (follow-up)

Number of subjects included in analysis

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.0022

Method

Fine and Gray

Parameter type

Hazard ratio (HR)

Point estimate

5.24

Confidence interval

level

95%

sides

2-sided

lower limit

1.82

upper limit

15.1

Adverse events

Top of page

Timeframe for reporting adverse events

Adverse events were collected up to 30 days following treatment cessation.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

Reporting group title

Adalimumab

Reporting group description

Adalimumab subcutaneous injection every 2 weeks for 18 months.

Reporting group title

Placebo

Reporting group description

Placebo subcutaneous injection every 2 weeks for 18 months

Serious adverse events	Adalimumab	Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	14 / 60 (23.33%)	2 / 30 (6.67%)
number of deaths (all causes)	0	0
number of deaths resulting from adverse events
Surgical and medical procedures
Antiviral prophylaxis
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Testes exploration
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorders
Syncope
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Eye disorders
Anterior chamber flare
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Cataract
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Uveitis
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Food poisoning
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Tonsillar hypertrophy
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Joint swelling
Additional description: This SAE occurred during follow-up and outside the reporting timelines as stated in the SYCAMORE protocol.
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Cellulitis
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infected bite
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Lower respiratory tract infection
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Scarlet fever
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Streptococcal infection
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Tonsillitis
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Varicella
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Viral infection
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	Adalimumab	Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	60 / 60 (100.00%)	26 / 30 (86.67%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma
subjects affected / exposed	5 / 60 (8.33%)	0 / 30 (0.00%)
occurrences all number	5	0
Surgical and medical procedures
Tonsillectomy
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
General disorders and administration site conditions
Chest discomfort
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Crying
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Drug intolerance
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Fatigue
subjects affected / exposed	1 / 60 (1.67%)	1 / 30 (3.33%)
occurrences all number	1	1
Feeling hot
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Hangover
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	2	0
Influenza like illness
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Injection site bruising
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences all number	3	0
Injection site erythema
subjects affected / exposed	3 / 60 (5.00%)	1 / 30 (3.33%)
occurrences all number	4	1
Injection site mass
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences all number	8	0
Injection site pain
subjects affected / exposed	5 / 60 (8.33%)	2 / 30 (6.67%)
occurrences all number	15	5
Injection site pruritus
subjects affected / exposed	3 / 60 (5.00%)	0 / 30 (0.00%)
occurrences all number	3	0
Injection site reaction
subjects affected / exposed	8 / 60 (13.33%)	0 / 30 (0.00%)
occurrences all number	40	0
Injection site swelling
subjects affected / exposed	4 / 60 (6.67%)	1 / 30 (3.33%)
occurrences all number	9	1
Injection site vesicles
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Malaise
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences all number	3	0
Pain
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	2	0
Pyrexia
subjects affected / exposed	15 / 60 (25.00%)	3 / 30 (10.00%)
occurrences all number	39	6
Swelling
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Immune system disorders
Immunisation reaction
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Seasonal allergy
subjects affected / exposed	3 / 60 (5.00%)	1 / 30 (3.33%)
occurrences all number	3	1
Reproductive system and breast disorders
Dysmenorrhoea
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	7	0
Pruritus genital
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	2	0
Vaginal lesion
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Vulvovaginal pruritus
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Respiratory, thoracic and mediastinal disorders
Adenoidal disorder
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Asthma
subjects affected / exposed	1 / 60 (1.67%)	1 / 30 (3.33%)
occurrences all number	1	2
Chronic obstructive pulmonary disease
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Cough
subjects affected / exposed	22 / 60 (36.67%)	3 / 30 (10.00%)
occurrences all number	32	3
Dyspnoea
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Epistaxis
subjects affected / exposed	3 / 60 (5.00%)	0 / 30 (0.00%)
occurrences all number	5	0
Nasal congestion
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Nasal discomfort
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences all number	4	0
Oropharyngeal pain
subjects affected / exposed	19 / 60 (31.67%)	2 / 30 (6.67%)
occurrences all number	43	3
Productive cough
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Rhinorrhoea
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Sinus congestion
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences all number	2	0
Snoring
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Wheezing
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Psychiatric disorders
Aggression
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Agitation
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Anxiety
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Emotional distress
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	2	0
Irritability
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	2	0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	6 / 60 (10.00%)	1 / 30 (3.33%)
occurrences all number	11	1
Aspartate aminotransferase abnormal
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Aspartate aminotransferase increased
subjects affected / exposed	5 / 60 (8.33%)	1 / 30 (3.33%)
occurrences all number	6	1
Blood alkaline phosphatase increased
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Blood glucose abnormal
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Blood potassium increased
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences all number	2	0
C-reactive protein abnormal
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
C-reactive protein increased
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences all number	2	0
Haematocrit abnormal
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Haemoglobin decreased
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Intraocular pressure increased
subjects affected / exposed	4 / 60 (6.67%)	0 / 30 (0.00%)
occurrences all number	7	0
Liver function test abnormal
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Neutrophil count decreased
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Red blood cell count abnormal
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Red blood cell sedimentation rate abnormal
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Red blood cell sedimentation rate increased
subjects affected / exposed	4 / 60 (6.67%)	1 / 30 (3.33%)
occurrences all number	5	1
Rubulavirus test positive
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Urine protein/creatinine ratio abnormal
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Vitamin D decreased
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Injury, poisoning and procedural complications
Animal bite
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Arthropod bite
subjects affected / exposed	2 / 60 (3.33%)	1 / 30 (3.33%)
occurrences all number	2	2
Arthropod sting
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Bite
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Contusion
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences all number	2	0
Fall
subjects affected / exposed	4 / 60 (6.67%)	0 / 30 (0.00%)
occurrences all number	4	0
Injury
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Joint dislocation
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	2
Joint injury
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Laceration
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	2	0
Ligament sprain
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences all number	2	0
Upper limb fracture
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Foreign body
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Nervous system disorders
Headache
subjects affected / exposed	15 / 60 (25.00%)	4 / 30 (13.33%)
occurrences all number	26	10
Hypoaesthesia
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Hyposmia
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Migraine
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	3	0
Paraesthesia
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences all number	3	0
Psychomotor hyperactivity
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Blood and lymphatic system disorders
Increased tendency to bruise
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Lymphadenopathy
subjects affected / exposed	3 / 60 (5.00%)	0 / 30 (0.00%)
occurrences all number	3	0
Neutropenia
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Ear and labyrinth disorders
Ear pain
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Eye disorders
Dry eye
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences all number	2	0
Eye discharge
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Eye inflammation
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Eye swelling
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences all number	2	0
Eyelid oedema
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Glaucoma
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Iridocyclitis
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Iris disorder
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Photopsia
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Uveitis
subjects affected / exposed	4 / 60 (6.67%)	4 / 30 (13.33%)
occurrences all number	4	4
Vision blurred
subjects affected / exposed	1 / 60 (1.67%)	1 / 30 (3.33%)
occurrences all number	1	1
Visual impairment
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Gastrointestinal disorders
Abdominal discomfort
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Abdominal pain
subjects affected / exposed	3 / 60 (5.00%)	0 / 30 (0.00%)
occurrences all number	4	0
Abdominal pain upper
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences all number	4	0
Constipation
subjects affected / exposed	2 / 60 (3.33%)	2 / 30 (6.67%)
occurrences all number	2	3
Dental caries
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences all number	2	0
Diarrhoea
subjects affected / exposed	7 / 60 (11.67%)	1 / 30 (3.33%)
occurrences all number	11	1
Dyspepsia
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Haematochezia
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Haemorrhoids
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Nausea
subjects affected / exposed	6 / 60 (10.00%)	2 / 30 (6.67%)
occurrences all number	10	2
Stomatitis
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Toothache
subjects affected / exposed	3 / 60 (5.00%)	0 / 30 (0.00%)
occurrences all number	4	0
Vomiting
subjects affected / exposed	19 / 60 (31.67%)	6 / 30 (20.00%)
occurrences all number	43	8
Skin and subcutaneous tissue disorders
Acne
subjects affected / exposed	1 / 60 (1.67%)	1 / 30 (3.33%)
occurrences all number	1	1
Dermatitis
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Erythema
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Ingrowing nail
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Night sweats
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Pruritus
subjects affected / exposed	1 / 60 (1.67%)	1 / 30 (3.33%)
occurrences all number	1	1
Rash
subjects affected / exposed	3 / 60 (5.00%)	2 / 30 (6.67%)
occurrences all number	6	2
Rash papular
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Swelling face
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	2	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	13 / 60 (21.67%)	2 / 30 (6.67%)
occurrences all number	25	3
Arthritis
subjects affected / exposed	1 / 60 (1.67%)	1 / 30 (3.33%)
occurrences all number	1	1
Back pain
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Joint stiffness
subjects affected / exposed	1 / 60 (1.67%)	1 / 30 (3.33%)
occurrences all number	1	1
Joint swelling
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Juvenile idiopathic arthritis
subjects affected / exposed	0 / 60 (0.00%)	2 / 30 (6.67%)
occurrences all number	0	2
Pain in extremity
subjects affected / exposed	2 / 60 (3.33%)	1 / 30 (3.33%)
occurrences all number	2	1
Pain in jaw
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Infections and infestations
Candida infection
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Cestode infection
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Conjunctivitis
subjects affected / exposed	3 / 60 (5.00%)	0 / 30 (0.00%)
occurrences all number	3	0
Conjunctivitis viral
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Ear infection
subjects affected / exposed	7 / 60 (11.67%)	2 / 30 (6.67%)
occurrences all number	8	2
Escherichia urinary tract infection
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	2	0
Eye infection
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Herpes simplex
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	6	0
Herpes zoster
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Impetigo
subjects affected / exposed	4 / 60 (6.67%)	1 / 30 (3.33%)
occurrences all number	5	1
Infected bite
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Infection
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Influenza
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Localised infection
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Lower respiratory tract infection
subjects affected / exposed	8 / 60 (13.33%)	2 / 30 (6.67%)
occurrences all number	9	4
Molluscum contagiosum
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences all number	2	0
Nasopharyngitis
subjects affected / exposed	17 / 60 (28.33%)	8 / 30 (26.67%)
occurrences all number	29	10
Oral herpes
subjects affected / exposed	3 / 60 (5.00%)	1 / 30 (3.33%)
occurrences all number	3	1
Otitis media
subjects affected / exposed	1 / 60 (1.67%)	1 / 30 (3.33%)
occurrences all number	1	1
Paronychia
subjects affected / exposed	3 / 60 (5.00%)	1 / 30 (3.33%)
occurrences all number	3	1
Pharyngitis
subjects affected / exposed	4 / 60 (6.67%)	0 / 30 (0.00%)
occurrences all number	4	0
Pneumonia
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Rhinitis
subjects affected / exposed	2 / 60 (3.33%)	1 / 30 (3.33%)
occurrences all number	2	1
Rubella
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Skin infection
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences all number	2	0
Staphylococcal infection
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Streptococcal infection
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Tonsillitis
subjects affected / exposed	13 / 60 (21.67%)	0 / 30 (0.00%)
occurrences all number	24	0
Tonsillitis streptococcal
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Upper respiratory tract infection
subjects affected / exposed	5 / 60 (8.33%)	1 / 30 (3.33%)
occurrences all number	8	1
Urethritis
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Urinary tract infection
subjects affected / exposed	10 / 60 (16.67%)	3 / 30 (10.00%)
occurrences all number	13	4
Varicella
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences all number	2	0
Viral infection
subjects affected / exposed	11 / 60 (18.33%)	1 / 30 (3.33%)
occurrences all number	15	1
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences all number	2	0
Dehydration
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

08 Sep 2011

The first amendment to the protocol made corrections to typographical errors in the original protocol.

30 Sep 2011

The second amendment added clarification to the Tissue Bank section, clarification to the primary endpoint section and introduction of endpoint for intermittent or continuous suspension of adalimumab/placebo, clarification that patients cannot have previously received adalimumab, addition of two further exclusion criteria points relating to intra-ocular pressure, removal of limit on how many times patients can be screened, addition of window for adalimumab/placebo injections, clarification of topical treatment after 3 months trial treatment, change to dose range of allowed methotrexate to 10-20mg/m2 and clarification of treatment timelines and visit windows.

25 Apr 2013

The third amendment to the protocol made changes to the monthly visit windows to allow a window of 7 days, clarified in the table of assessments that CSRI questionnaire is completed at baseline only, changed the timeline for tuberculosis assessment from 4 weeks to 12 weeks prior to baseline and clarified that haematological and biochemical samples taken at screening can be used for the baseline visit.

25 Sep 2013

The fourth amendment to the protocol reduced the sample size from 154 to 114 and the duration of follow up post treatment from 18 months to 6 months, changed the assessment of reduction of vision from number of letters to LogMAR units, clarification to inclusion and exclusion criteria, addition of systemic acetazolamide as medication not permitted, removal of the collection of human anti-human antibody samples, window for methotrexate administration added, change to the collection of routine patient-level information and costing systems (PLICS) data and clarification on definition of end of trial added.

11 Aug 2014

The fifth amendment to the protocol added text to say that the IDSMC may request an interim analysis of the primary outcome.

11 Aug 2014

The sixth change to the protocol clarified that patients are classed as withdrawals and not treatment failures if they miss more than 4 weeks of methotrexate treatment, added further clarification that haematological and biochemical blood results can be used for baseline if taken at screening only if assessment was completed within the previous 15 days, clarification added to Tissue Bank samples to state that 3 months sample should be taken at the very next opportunity if not taken at 3 months and that the 18 months samples should be taken if patient ends treatment early.

17 Apr 2015

The seventh change to the protocol stated that the blinded phase of the trial has been stopped, all patients on adalimumab will continue to be treated but patients on placebo will stop treatment and proceed to follow up.

14 Jul 2016

The eighth change to the protocol clarified that JADAS was a secondary outcome and SAE reporting procedures.

Were there any global interruptions to the trial? Yes

Date	Interruption	Restart date
17 Apr 2015	Following the results of an interim analysis, the IDSMC recommended that recruitment to SYCAMORE stop and the allocations of patients who were currently in the trial be unblinded. They recommended that patients who were on placebo stop taking the allocated treatment and enter the 6 month follow-up period of the trial (treatment of these patients was then at the discretion of the treating clinician). Patients who were on adalimumab were to continue on their allocated treatment as per protocol in an ‘open label’ fashion. Following completion of this ‘open label’ period, adalimumab patients entered the 6 month follow-up period. The IDSMC recommended that the results of the double blind period be made publically available. On the 17th April 2015, following the IDSMC recommendation, the TSC made the decision to unblind the trial.	-

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

N/A

http://www.ncbi.nlm.nih.gov/pubmed/28445659

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: Randomised Control Trial of the Clinical Effectiveness, Safety and Cost Effectiveness of Adalimumab in Combination with Methotrexate for the Treatment of Juvenile Idiopathic Arthritis Associated Uveitis.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Blinded Phase: Time to treatment failure

Primary: Blinded Phase: Time to treatment failure

Secondary: Blinded phase: Number of participants failing treatment

Secondary: Blinded phase: Number of participants failing treatment

Secondary: Blinded phase: Total oral corticosteroid dose

Secondary: Blinded phase: Total oral corticosteroid dose

Secondary: Blinded phase: Reduction in systemic corticosteroid dose from entry dose to 0mg

Secondary: Blinded phase: Reduction in systemic corticosteroid dose from entry dose to 0mg

Secondary: Blinded phase: Rate of systemic corticosteroid dose from entry dose

Secondary: Blinded phase: Rate of systemic corticosteroid dose from entry dose

Secondary: Blinded phase: Time to reduction to <2 drops in topical corticosteroids

Secondary: Blinded phase: Time to reduction to <2 drops in topical corticosteroids

Secondary: Blinded phase: Need for pulsed corticosteroid

Secondary: Blinded phase: Need for pulsed corticosteroid

Secondary: Blinded phase: Optic and Ocular: Number of participants with disease flares following a minimum of 3 months of disease control

Secondary: Blinded phase: Optic and Ocular: Number of participants with disease flares following a minimum of 3 months of disease control

Secondary: Blinded phase: Optic and Ocular: Number of participants with disease flares within the first 3 months of the study

Secondary: Blinded phase: Optic and Ocular: Number of participants with disease flares within the first 3 months of the study

Secondary: Blinded phase: Optic and Ocular: Visual acuity as measured by age-appropriate LogMAR assessment

Secondary: Blinded phase: Optic and Ocular: Visual acuity as measured by age-appropriate LogMAR assessment

Secondary: Blinded phase: Optic and Ocular: Number of participants with resolution of associated optic nerve

Secondary: Blinded phase: Optic and Ocular: Number of participants with resolution of associated optic nerve

Secondary: Blinded phase: Optic and Ocular: Number of participants with resolution of macular oedema

Secondary: Blinded phase: Optic and Ocular: Number of participants with resolution of macular oedema

Secondary: Blinded phase: Optic and Ocular: Number of participants with disease control for 3 months

Secondary: Blinded phase: Optic and Ocular: Number of participants with disease control for 3 months

Secondary: Blinded phase: Optic and Ocular: Number of participants with disease control for 6 months

Secondary: Blinded phase: Optic and Ocular: Number of participants with disease control for 6 months

Secondary: Blinded phase: Optic and Ocular: Number of participants entering disease remission for 3 months

Secondary: Blinded phase: Optic and Ocular: Number of participants entering disease remission for 3 months

Secondary: Blinded phase: Optic and Ocular: Number of participants entering disease remission for 6 months

Secondary: Blinded phase: Optic and Ocular: Number of participants entering disease remission for 6 months

Secondary: Blinded phase: Optic and Ocular: Duration of sustaining inactive disease

Secondary: Blinded phase: Optic and Ocular: Duration of sustaining inactive disease

Secondary: Blinded phase: Quality of life assessments: Childhood Health Questionnaire (CHQ)

Secondary: Blinded phase: Quality of life assessments: Childhood Health Questionnaire (CHQ)

Secondary: Blinded phase: Quality of life assessments: Childhood Health Assessment Questionnaire (CHAQ)

Secondary: Blinded phase: Quality of life assessments: Childhood Health Assessment Questionnaire (CHAQ)

Secondary: Blinded phase: American College of Rheaumatology (ACR) score

Secondary: Blinded phase: American College of Rheaumatology (ACR) score

Secondary: Blinded phase: Number of participants undergoing disease flares

Secondary: Blinded phase: Number of participants undergoing disease flares

Secondary: Blinded phase: Number of participants with minimum disease activity

Secondary: Blinded phase: Number of participants with minimum disease activity

Secondary: Blinded phase: Number of participants requiring change in biologic and/or DMARD therapy for arthritis due to failure to respond

Secondary: Blinded phase: Number of participants requiring change in biologic and/or DMARD therapy for arthritis due to failure to respond

Secondary: Blinded phase: Participants score of the Juvenile Arthritis Disease Activity Score (JADAS)

Secondary: Blinded phase: Participants score of the Juvenile Arthritis Disease Activity Score (JADAS)

Secondary: Blinded phase: Compliance according to participant diaries

Secondary: Blinded phase: Compliance according to participant diaries

Secondary: Blinded phase: Compliance according to accountability logs

Secondary: Blinded phase: Compliance according to accountability logs

Secondary: Blinded phase: Laboratory parameters

Secondary: Blinded phase: Laboratory parameters

Secondary: Blinded phase: Incremental cost-effectiveness and cost utility

Secondary: Blinded phase: Incremental cost-effectiveness and cost utility

Secondary: Follow-up phase: Use of corticosteroids over duration of study period (blinded, open label and follow up phase)

Secondary: Follow-up phase: Use of corticosteroids over duration of study period (blinded, open label and follow up phase)

Secondary: Follow-up phase: Reduction in systemic corticosteroid dose from entry dose to 0mg

Secondary: Follow-up phase: Reduction in systemic corticosteroid dose from entry dose to 0mg

Secondary: Follow-up phase: Reduction in systemic corticosteroid dose from entry dose to <5mg

Secondary: Follow-up phase: Reduction in systemic corticosteroid dose from entry dose to <5mg

Secondary: Follow-up phase: Time to reduction to <2 drops in topical corticosteroids

Secondary: Follow-up phase: Time to reduction to <2 drops in topical corticosteroids

Secondary: Follow-up phase: Need for pulsed corticosteroid

Secondary: Follow-up phase: Need for pulsed corticosteroid

Secondary: Follow-up phase: Laboratory parameters

Secondary: Follow-up phase: Laboratory parameters

Secondary: Blinded phase: Reduction in systemic corticosteroid dose from entry dose to <5mg

Secondary: Blinded phase: Reduction in systemic corticosteroid dose from entry dose to <5mg

Clinical Trial Results:
Randomised Control Trial of the Clinical Effectiveness, Safety and Cost Effectiveness of Adalimumab in Combination with Methotrexate for the Treatment of Juvenile Idiopathic Arthritis Associated Uveitis.