Safety and Efficacy of Tofacitinib in the Treatment of NSAID Refractory Axial Spondyloarthritis:A Clinical Trial

• Status: Unknown status
• Trial end date: 2018-12-31
• Target enrollment: 0
• Participant gender: All

Summary

Title Efficacy and Safety of Tofacitinib in the Treatment of NSAID-Refractory Axial Spondyloarthritis: A Clinical Trial

Background:

Axial spondyloarthritis (axSpA) is a chronic systemic inflammatory rheumatic disease affecting mainly sacroiliac joints and spine. There are limited options for treatment. Initial treatments are patient's education, regular physical exercise and nonsteroidal antiinflammatory drugs(NSAID). If the patients do not respond to at least two NSAIDs in full dosages for at least one month then it is called NSAID refractory axSpA. In these cases biologics like-tumor necrosis factor α blockers are the options for treatment. Tofacitinib is a new drug has been proven to be effective for treatment of rheumatoid arthritis , psoriasis , inflammatory bowel disease and supposed to be effective in spondyloarthritis. This study is aimed to assess the efficacy and safety of tofacitinib in NSAID refractory ax SpA with a view to find a safe, effective and affordable treatment modality.

Method:

This open label uncontrolled clinical trial with tofacitinib will be conducted in NSAID refractory axSpA (age >18 years) patients. Study participants will be enrolled after having informed written consent from the outpatient department of Rheumatology, Bangabandhu sheikh mujib medical university. Assessment of Spondyloarthritis International Society (ASAS) criteria will be followed for diagnosis of ax SpA. Patients failing a trial of 2 different NSAID each for at least 2 weeks with optimum dosage without response or with partial response and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of ≥4 (range, 0-10) or Ankylosing spondylitis disease activity score-C reactive protein(ASDAS-CRP)>2.1 will be considered as primary entry criteria for this study.

Baseline evaluation will include Bath AS Disease Activity Index (BASDAI), Functional Index (BASFI) , Ankylosing spondylitis disease activity score-C reactive protein(ASDASCRP) and Ankylosing spondylitis disease activity score-erythrocyte sedimentation rate(ASDAS-ESR).

Laboratory tests like CBC, ESR, CRP, SGPT, Serum creatinine and X-ray pelvis A/P view or X-ray both SI joints modified Ferguson veiw (to see both SI and hip joints ), HLA-B27(if needed), CXR P/A view and MT test or Interferon Gamma Release Assay(IGRA) will be done.

After considering inclusion and exclusion criteria eligible patients will be included for this study. All patients will be put on 5mg tofacitinib BD. NSAID and adjuvant analgesics will be used if needed. Follow up will be done at 4th, 12th and 24th week. Response to treatment will be evaluated by assessement of spondyloarthritis society (ASAS) response criteria. More than 20% improvements from baseline will consider as primary response at the end of 12th week. Those patients who will not achieve ASAS20 response at 12th week, will be given 10 mg tofacitinib BD. Efficacy will be assessed at the end of 24th week by ASAS20, ASAS50, ASAS70, ASDAS-ESR, ASDAS-CRP, BASDAI, Bath ankylosing spondylitis functional index(BASFI). Adverse effects will be assesed by history, Physical examinations and investigations.

The entire study subjects will be informed about the nature, purpose and implication of the study as well as whole spectrum of benefits and risk of the study. Ethical clearance will be taken from the IRB of BSMMU.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Globe Pharmaceuticals Limited
• Collaborator: Globe pharmaceuticals Ltd, Dhaka, Bangladesh
• Treatments: Tofacitinib

Criteria

Inclusion Criteria:

• The subjects will be considered if they fulfill the following criteria

1. Subjects greater than 18 years of age

2. Patients fulfilling the ASAS classification criteria for axial SpA including both non radiographic axial spondyloarthritis (nr-Ax SpA) and ankylosing spondylitis(AS)

3. Patients with axSpA underwent a trial of at least 2 course of NSAIDs with optimum doses for at least 1 month without response or with partial response

4. Patients with BASDAI ≥4 or ASDAS-CRP>2.1

Exclusion Criteria:

• The subjects will be excluded if they have any of the

1. Systemic infections requiring hospital admission during the last 6 months

2. Active infections and/or a history of chronic or recurrent serious infective diseases, opportunistic infections

3. Hemoglobin (Hb) < 9 g/dl

4. White blood cell count < 4000, Neutrophil count < 1000, Platelet count < 100000/mm3

5. Live vaccines within 3 months prior to the first dose

6. Serum creatinine > upper limit of normal reference range

7. GFR less than 50 mL/min

8. Alanine aminotransaminase (ALT) more than 2 times of ULN

9. Pregnant or breast feeding females of child-bearing potential not using highly effective contraception

10. Evidence or history of malignancy, with the exception of adequately treated or excised non-metastatic basal or squamous cell cancer of the skin or cervical carcinoma in situ

11. New York Heart Association Class III and IV congestive heart failure

12. Any lymphoproliferative disorder, history of lymphoma, leukemia, or signs and symptoms suggestive of current lymphatic disease