Axial Spondyloarthritis Clinical Trial
Official title:
Safety and Efficacy of Tofacitinib in the Treatment of NSAID Refractory Axial Spondyloarthritis:A Clinical Trial
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.
Status | Recruiting |
Enrollment | 30 |
Est. completion date | December 31, 2018 |
Est. primary completion date | December 30, 2018 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility |
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 |
Country | Name | City | State |
---|---|---|---|
Bangladesh | Bangabandhu sheikh mujib medical university | Dhaka |
Lead Sponsor | Collaborator |
---|---|
Globe Pharmaceuticals Limited | Globe pharmaceuticals Ltd, Dhaka, Bangladesh |
Bangladesh,
Anderson JJ, Baron G, van der Heijde D, Felson DT, Dougados M. Ankylosing spondylitis assessment group preliminary definition of short-term improvement in ankylosing spondylitis. Arthritis Rheum. 2001 Aug;44(8):1876-86. — View Citation
Boonen A, van der Heijde D, Landewé R, Guillemin F, Rutten-van Mölken M, Dougados M, Mielants H, de Vlam K, van der Tempel H, Boesen S, Spoorenberg A, Schouten H, van der Linden S. Direct costs of ankylosing spondylitis and its determinants: an analysis among three European countries. Ann Rheum Dis. 2003 Aug;62(8):732-40. — View Citation
Braun J, Inman R. Clinical significance of inflammatory back pain for diagnosis and screening of patients with axial spondyloarthritis. Ann Rheum Dis. 2010 Jul;69(7):1264-8. doi: 10.1136/ard.2010.130559. Review. — View Citation
Braun J, Pham T, Sieper J, Davis J, van der Linden S, Dougados M, van der Heijde D; ASAS Working Group. International ASAS consensus statement for the use of anti-tumour necrosis factor agents in patients with ankylosing spondylitis. Ann Rheum Dis. 2003 Sep;62(9):817-24. Review. — View Citation
Sykes WS, Lawrence RC. Helium in Anaesthesia. Br Med J. 1938 Aug 27;2(4051):448-9. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Assessment of spondyloarthritis international society 20 response(ASAS 20) | ASAS 20:It is a composite measurement which means improvement of = 20% in 3 of the following 4 domains without 20% worsening in the remaining domain Four domains Bath ankylosing spondylitis functional index(BASFI)-The 10 items index of daily functional activities completed on a numerical rating scale (NRS) 0-10. The higher the BASFI score, the more severe the limitation of function due to AxSpA Morning stiffness Patient global assessment Pain |
At the end of 3rd month | |
Secondary | Ankylosing Spondylitis Disease Activity Score- C reactive protein(ASDASCRP) | ASDAS-CRP: 0.121×total back pain+0.110×patient global+0.073×peripheral pain/swelling+0.058×duration of morning stiffness+0.579×Ln(CRP+1). | At the end of 6 month | |
Secondary | Ankylosing Spondylitis Disease Activity Score-Erythrocyte sedimentation rate(ASDASESR) | ASDAS-ESR: 0.113×patient global+0.293xESR----v+0.086×peripheral pain/swelling+0.069×duration of morning stiffness+0.079×total back pain. | At the end of 6th month |
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