Tofacitinib demonstrated very promising results for oral treatment of active ankylosing spondylitis in a phase 3 trial. New safety risks were not detected.
Several types of immune cells playing a role in the pathogenesis of spondyloarthritis use JAK pathways [1]. Hence, not surprisingly, JAK inhibitors such as tofacitinib have already shown promising results in phase 2 trials for ankylosing spondylitis (AS) and therefore have potential to become a therapeutic option for this indication in the future [2,3].
The oral JAK inhibitor tofacitinib is now investigated in phase 3 for the treatment of AS [4]. This randomised, placebo-controlled, double-blind study included 269 adult patients with active AS, who met the modified New York criteria in centrally read radiographs. All patients had inadequate response or were intolerant to treatment with at least 2 non-steroidal anti-inflammatory drugs (NSAIDs). A primary analysis of the still ongoing trial was reported.
Over 16 weeks, study subjects were either treated with twice daily 5 mg tofacitinib or placebo. In the following open-label extension, all patients received 5 mg tofacitinib twice daily until week 48. The primary endpoint was defined as Assessment in Ankylosing Spondylitis (ASAS)20 response at week 16. The key secondary endpoint was ASAS40 achievement. Furthermore, 4 groups of endpoints for efficacy were evaluated at week 16, including change in various outcome types. Safety data was available up to week 48.
Baseline patient characteristics were: 85% males, the average age was 41, symptom duration was ~13 years, Ankylosing Spondylitis Disease Activity Score (ASDAS) was 3.8 for the group receiving tofacitinib and 3.9 for the group receiving placebo. âThe majority of patients (80%) were naĂŻve to biologic disease-modifying antirheumatic drugs (DMARDs) and 20% were inadequate responders to TNF inhibitors or had experienced biologic DMARDs in the past,â explained Prof. Atul Deodhar (Oregon Health & Science University, USA).
The rate of patients achieving an ASAS20 response at week 16 was 56.4% with tofacitinib and 29.4% with placebo (P<0.0001; see Figure). Furthermore, the percentage of ASAS40-responding patients at week 16 was significantly higher in those treated with tofacitinib (40.6%) than in those receiving placebo (12.5%; P<0.0001). ASDAS was significantly reduced by 1.36 for tofacitinib versus 0.39 for placebo (P<0.001). Comparisons for the ASAS components as well as various other secondary endpoints including CRP reduction were all significant in favour of tofacitinib treatment.
Figure. Tofacitinib in ankylosing spondylitis: primary and key secondary endpoints were achieved [4]
ASAS, Assessment in Ankylosing Spondylitis; BID, twice daily.
Concerning safety up to week 16, adverse events (AEs) were registered for 54.1% in the tofacitinib and 51.5% in the placebo group, with rates for serious AEs of 1.5% and 0%, respectively. Study discontinuation due to AEs at week 16 was low: 2.3% for tofacitinib versus 0.7% for placebo. âThere were no unexpected side effects in this study,â said Prof. Deodhar. Concerning safety up to week 48, he further elaborated: âThere were no malignancies, no thromboembolic events, no major adverse cardiac events, and no gastrointestinal perforations.â
In conclusion, the study met its primary and secondary endpoints with the demonstration of significant superiority of tofacitinib over placebo in the treatment of active AS and adds to the body of literature supporting the efficacy of JAK inhibition in AS and the seronegative spondyloarthropathies.
- Veale DJ, et al. Rheumatology (Oxford). 2019;58:197-205
- Van der Heijde D, et al. Ann Rheum Dis. 2017;76:1340-7.
- Poddubnyy D, Sieper J. Curr Rheumatol Rep. 2020;22:47
- Deodhar A, et al. Tofacitinib for the treatment of adult patients with ankylosing spondylitis: primary analysis of a phase 3, randomized, double-blind, placebo-controlled study. L11, ACR Convergence 2020, 5-9 Nov.
- Presented By
- Prof. Thomas MacDonald, University of Dundee, UK
- Presented By
- Dr Maria Cinta Cid, Hospital ClĂnic of Barcelona, Spain
- Presented By
- Prof. Dinesh Khanna, University of Michigan Scleroderma Program, USA
- Presented By
- Prof. Atul Deodhar, Oregon Health & Science University, USA
- Presented By
- Prof. Josef Smolen, Medical University of Vienna, Austria
- Presented By
- Prof. Daniel Aletaha, Medical University Vienna, Austria
- Presented By
- Prof. Joan Bathon, Columbia University, USA
- Presented By
- Dr Akhil Sood, University of Texas Medical Branch, USA
- Presented By
- Prof. Rebecca Grainger, University of Otago, New Zealand
- Presented By
- Dr Naomi Serling-Boyd, Massachusetts General Hospital, USA
- Presented By
- Prof. Chaim Putterman, Albert Einstein College of Medicine, USA
- Presented By
- Prof. Joan T. Merrill, Oklahoma Medical Research Foundation, USA
- Presented By
- Prof. Denis Poddubnyy, Charité UniversitÀtsmedizin Berlin, Germany
- Presented By
- Prof. Dennis McGonagle, University of Leeds, UK
- Presented By
- Prof. Philip J. Mease, University of Washington, USA
- Presented By
- Dr Anisha Dua, Northwestern Medical Group, USA
- Presented By
- Dr Peter Grayson, National Institutes of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH, USA
- Presented By
- Prof. Biswadip Ghosh, Institute of Post Graduate Medical Education and Research, India
- Presented By
- Dr Priyanka Ballal, Boston University Medical Center, USA
- Presented By
- Prof. Jinoos Yazdany, University of California San Francisco, USA
- Presented By
- Dr Giovanni Adami, University of Verona, Italy
- Presented By
- Dr Justin J. Bucci, Boston University School of Medicine, USA
- Presented By
- Dr Elizabeth Park, Columbia University Irving Medical Center, USA
- Presented By
- Dr Jonathan S. Hausmann, Harvard Medical School and Boston Childrenâs Hospital, USA
- Presented By
- Ms Emily Sirotich, COVIDâ19 Global Rheumatology Alliance Steering Committee and McMaster University, Canada
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Table of Contents: ACR 2020
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Late-Breaking News
Gout treatment with febuxostat: no higher cardiovascular mortality
New agent with great potential for the treatment of giant cell arteritis in the pipeline
Autotaxin inhibitor successful in the first trial in diffuse cutaneous systemic sclerosis
JAK inhibition as a treatment option for ankylosing spondylitis
Spotlight on Rheumatoid Arthritis
Persuasive long-term results for JAK inhibition in rheumatoid arthritis
Rheumatoid arthritis: new EULAR treatment guidelines
Rheumatoid arthritis and interstitial lung disease: a deadly combination
COVID-19 â What Rheumatologists Need to Know
COVID-19 in patients with rheumatic disease: most report mild disease
Poor disease control: a risk factor for severe COVID-19
No heightened outcome risk for rheumatic patients with COVID-19
What Is Hot in Lupus Nephritis?
Lupus nephritis biomarkers: moving toward an omic-driven approach
Lupus nephritis: new therapies on the horizon in 2020
Spondyloarthritis â The Beat Goes On
Artificial intelligence can help in the diagnosis of axSPA
Resolution of dactylitis or enthesitis is associated with improvements in joint and skin symptoms
Promising novel treatment option for psoriatic arthritis
How to Diagnose Large Vessel Vasculitis: Promises and Pitfalls
How to choose imaging modalities in large vessel vasculitis
Diagnosis of large vessel vasculitis with imaging
Osteoarthritis â Novel Developments
Knee osteoarthritis patients with indicators of inflammation could profit from methotrexate
Anticoagulation with vitamin K antagonist is associated with risk of knee and hip replacement
Osteoporosis â New Data
Bisphosphonate use: Asian American women have a smaller treatment benefit
Inflammatory disease as a risk factor for fractures
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Hydroxychloroquine use: no indication for arrhythmias in RA and SLE patients
Children with rheumatic disease have no greater risk of a COVID-19 infection
Insufficient antimalarial supply for rheumatic disease treatment in the early COVID-19 pandemic
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