Psoriatic Arthritis, Sacroilitis, Spondylitis
Conditions
Keywords
Psoriatic Arthritis, Sacroiliitis, Spondylitis, MRI
Brief summary
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
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.
Interventions
DRUGTofacitinib 5 MG Oral Tablet [Xeljanz]
verum tablets
DRUGPlacebo oral tablet
tablets containing placebo
Sponsors
Charite University, Berlin, Germany
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Placebo controlled parallel group for 12 weeks followed by 12 weeks open label
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MRI Berlin Score | Week 12 vs Baseline | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Responses in ASAS Health Index | Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 | 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). |
| Responses in ASDAS | Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 | 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. |
| Responses in BASDAI | Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 | Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Calculated score from 6 questions VAS; range 0-10, the higher the worse. |
| Responses in BASFI | Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 | Bath Ankylosing Spondylitis Functional Index (BASFI). Mean of 10 questions VAS, range 0-10; higher value = more impaired function. |
| Responses in BASMI(lin) | Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 | 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. |
| Responses in HAQ-DI | Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 | 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. |
| Responses in Patient Global Score | Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 | Patient Global Score of overall disease activity - VAS 0-10 (higher = worse) |
| The Assessment of Spondyloarthritis International Society (ASAS) response criteria | Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 | 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). |
| Responses in DAPSA | Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 | 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). |
| Responses in PASI | Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 | Psoriasis Area and Severity Index (PASI) - description of skin involvement regarding scaling, redness, thickness and body surface area. Range 0-72. |
| Responses in MASES | Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 | Maastricht Ankylosing Spondylitis Enthesitis Score (MASES;Heuft-Dorenbosch Ann Rheum Dis 2003). Assessing 13 clinical enthesial sites (yes / no). Range 0-13. |
| Response in CRP | Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 | C-reactive protein (CRP, mg per litre) |
| Response in ESR | Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 | Erythrocyte Sedimentation Rate (ESR, mm per 1 hour) |
| MRI Berlin Score | Week 24 vs Baseline, Week 24 vs Week 12 | Improvement of the Berlin MRI score (description see primary outcome) for sacroiliac joints and spine |
| Responses in Physician Global Score | Week 12 vs Baseline, Week 24 vs Baseline, Week 24 vs Week 12 | Physician Global Score of overall disease activity - VAS 0-10 (higher = worse). |
Countries
Germany
Contacts
Primary ContactFabian N Proft, MD
Backup ContactBianca Mandt, SN
Outcome results
None listed