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).
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
80
verum tablets
tablets containing placebo
Charite University, Rheumatology CCM
Berlin, Germany
RECRUITINGPraxis für Rheumatologie
Berlin, Germany
RECRUITINGCharite University - Dept. Rheumatology CBF
Berlin, Germany
RECRUITINGUniversity Cologne, Dept. Rheumatology
Cologne, Germany
RECRUITINGUniklinik, Forschungszentrum Rheumatologie
Düsseldorf, Germany
RECRUITINGPraxis Dilltal
Ehringshausen, Germany
RECRUITINGUniklinikum, Med. Klinik 3
Erlangen, Germany
RECRUITINGCIRI Zentrum f innovative Diagnsotik und Therapie
Frankfurt am Main, Germany
RECRUITINGUniklinikum, Dept. Rheumatologie
Freiburg im Breisgau, Germany
RECRUITINGHamburger Rheumaforschungszentrum
Hamburg, Germany
RECRUITING...and 9 more locations
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).
Time frame: Week 12 vs Baseline
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).
Time frame: 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).
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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)
Time frame: 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).
Time frame: 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).
Time frame: 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.
Time frame: 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.
Time frame: Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12
Response in CRP
C-reactive protein (CRP, mg per litre)
Time frame: Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12
Response in ESR
Erythrocyte Sedimentation Rate (ESR, mm per 1 hour)
Time frame: 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
Time frame: Week 24 vs Baseline, Week 24 vs Week 12
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