Tofacitinib for Reduction of Spinal Inflammation in Patients With Psoriatic ArthritiS PresenTing With Axial InvOlvement

Study Overview
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Brief Summary
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To evaluate the efficacy of Tofacitinib in reducing inflammation in the sacroiliac joints and spine on magnetic resonance imaging (MRI) in patients with active Psoriatic Arthritis (PsA) with axial Involvement (BASDAI [Bath Ankylosing Spondylitis Disease Activity Index] ≥ 4 and total backpain ≥ 4 despite treatment with NSAIDs plus evidence of active inflammation in the sacroiliac joints or spine on MRI).

Detailed Description
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This study is a prospective, randomized, double-blind, placebo-controlled, multicenter study to investigate the efficacy of Tofacitinib in reducing inflammation in the sacroiliac joints and in the spine on MRI in patients with active axial PsA. Eligible patients (n=80) will be randomized 1:1 to receive either Tofacitinib 5mg orally twice daily or placebo for a 12-week period. After week 12, all patients will receive Tofacitinib 5mg orally twice daily for another 12 weeks. The study duration will include a 6-week screening period, a 24-week treatment period and a safety follow-up period of 4 weeks. Patients will be closely monitored throughout the study on a total of 11 visits. Safety data will be collected in the form of adverse events, vital parameters, physical examinations, and laboratory parameters throughout the study. The baseline MRI of the whole spine and sacroiliac (SI) joints will be performed within the 6-week screening period to confirm the presence of active inflammation (bone marrow edema) compatible with Spondyloarthritis (will be assessed by a central reader), at week 12 to evaluate the primary study endpoint, and at week 24 to evaluate the secondary endpoint. The primary study endpoint will be an improvement of the total Berlin MRI score for sacroiliac joints and spine at week 12 as compared to baseline.

Official Title
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Efficacy of Tofacitinib in Reduction of Inflammation Detected on MRI in Patients With Psoriatic ArthritiS PresenTing With Axial InvOlvement - a Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial

Conditions
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Psoriatic Arthritis, Spondylitis, Sacroilitis

Intervention / Treatment
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* Drug: Tofacitinib 5 MG Oral Tablet [Xeljanz]
* Drug: Placebo oral tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Psoriatic Arthritis fulfilling ClASsification for Psoriatic ARthritis (CASPAR) criteria chronic back pain > 3 months BASDAI value ≥ 4 and backpain ≥ 4 / 10 VAS presence of active inflammation in Screening MRI of sacroiliac joints and / or spine (central reading) history of inadequate response to ≥ 2 NSAIDs or intolerance / contraindications Exclusion Criteria: active current infection, severe infections in the last 3 months history of recurrent Herpes zoster or disseminated Herpes simplex immunodeficiency chronic Hepatitis B, C or HIV infection women: pregnant or lactating (have to practice reliable method of contraception) other severe diseases conflicting with a clinical study, contraindications for MRI

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Placebo controlled parallel group for 12 weeks followed by 12 weeks open label
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Tofacitinib<br>5 mg oral BID | Drug: Tofacitinib 5 MG Oral Tablet [Xeljanz]<br>* verum tablets<br>* Other names: Xeljanz;|
| Placebo Comparator: Placebo<br>matching Placebo BID | Drug: Placebo oral tablet<br>* tablets containing placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MRI Berlin Score | Improvement of the Berlin MRI score for sacroiliac joints and spine. Scoring includes spinal inflammation (Lucas C et al, J Rheumatol 2007): 23 vertebral units with semiquantitative range of inflammation between 0 to 3 (min. score = 0, max. score = 69, the higher the worse). Additionally, inflammation of the sacroiliac joints is scored (Hermann KG, Rheumatologe 2004; scoring each quadrant between 0 and 4, max. score 16, the higher, the worse). | Week 12 vs Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Assessment of Spondyloarthritis International Society (ASAS) response criteria | Assessment of Spondyloarthritis International Society Response Criteria (Anderson JJ, Arthritis Rheum 2001): change in percent of at least 3 of 4 subcores (Patient Global VAS, Pain VAS, BASFI and BASDAI questions 5&6). | Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 | 
| Responses in ASAS Health Index | Assessment of Spondyloarthritis International Society ASAS Health Index (Kiltz U, Ann Rheum Dis 2015). Consisting of 17 questions answered, calculated in percent (100 % = best spondylarthritis related health). | Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 | 
| Responses in ASDAS | Ankylosing Spondylitis Disease Activity Score (ASDAS) combining 3 questions VAS (back pain, peripheral pain and morning stiffness) with CRP or ESR; formulas used as described in Lucas C, Ann Rheum Dis 2009. Values <1.3 inactive disease, <2.1 low disease activity, 2.1-3.5 high disease activity, >3.5 very high disease activity. | Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 | 
| Responses in BASDAI | Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Calculated score from 6 questions VAS; range 0-10, the higher the worse. | Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 | 
| Responses in BASFI | Bath Ankylosing Spondylitis Functional Index (BASFI). Mean of 10 questions VAS, range 0-10; higher value = more impaired function. | Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 | 
| Responses in BASMI(lin) | Bath Ankylosing Spondylitis Metrology Index - linear score (BASMI; van der Heijde Ann Rheum Dis 2008). Measuring Schober´s test (cm), intermalleolar distance (cm), cervical rotation (degree), lateral lumbar flexion (cm) and tragus-to-wall-distance (cm) and calculate the score as reported in the citation. | Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 | 
| Responses in HAQ-DI | Health assessment questionnaire disability index (HAQ-DI; Princus T, Arthritis Rheum 1983) measuring influence of arthritis on quality of life. Patient questionnaire recalculated in scores 0 to 3, higher = worse. | Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 | 
| Responses in Patient Global Score | Patient Global Score of overall disease activity - VAS 0-10 (higher = worse) | Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 | 
| Responses in Physician Global Score | Physician Global Score of overall disease activity - VAS 0-10 (higher = worse). | Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 | 
| Responses in DAPSA | Disease Activity in PSoriatic Arthritis (DAPSA; Schoels M, Arthritis Rheum 2010); calculated by summing swollen joint count (max. 66) + tender joint count (max. 68) + patient pain VAS + patient global assessments VAS + CRP. Value ranges 0 to >28 (the higher, the worse). | Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 | 
| Responses in PASI | Psoriasis Area and Severity Index (PASI) - description of skin involvement regarding scaling, redness, thickness and body surface area. Range 0-72. | Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 | 
| Responses in MASES | Maastricht Ankylosing Spondylitis Enthesitis Score (MASES;Heuft-Dorenbosch Ann Rheum Dis 2003). Assessing 13 clinical enthesial sites (yes / no). Range 0-13. | Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 | 
| Response in CRP | C-reactive protein (CRP, mg per litre) | Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 | 
| Response in ESR | Erythrocyte Sedimentation Rate (ESR, mm per 1 hour) | Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 | 
| MRI Berlin Score | Improvement of the Berlin MRI score (description see primary outcome) for sacroiliac joints and spine | Week 24 vs Baseline, Week 24 vs Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MRI, Psoriatic Arthritis, Sacroiliitis, Spondylitis