The small molecule deucravacitinib led to a significantly better ACR20 response and better physical function independent of prior TNF inhibitor use in 180 psoriatic arthritis patients in a randomised, double-blind, placebo-controlled phase 2 trial.
Deucravacitinib (formerly BMS-986165) is a novel oral tyrosine kinase (TYK)2 inhibitor. It is far more selective than other drugs in this class, as it does not bind to the kinase domain, but only to a regulatory domain of TYK2 outside the active site [1]. Thus, it inhibits downstream pathways important in psoriasis and psoriatic arthritis (PsA) pathophysiology, including interleukin (IL)-23 and IL-22, while limiting off-target effects observed with other kinase inhibitors. In an earlier phase 2 dose-finding study in psoriasis, this drug showed to be significantly more effective compared with placebo: 67-75% of patients treated with ≥3 mg deucravacitinib achieved a ≥75% reduction from baseline in Psoriasis Area and Severity Index (PASI)75 at 12 weeks (vs 7% with placebo; P<0.001) with only mild-to-moderate adverse events. During the meeting, Prof. Philip J. Mease (University of Washington, USA) presented results from the initial 16-week placebo-controlled phase of a phase 2 trial (NCT03881059) that evaluated the efficacy and safety of the selective TYK2 inhibitor in patients with active PsA.
The 16 weeks of treatment were completed by 180 of 203 patients (89%). Baseline characteristics were comparable between all groups. An inadequate response to TNF inhibitors was observed in 15% of patients. Both deucravacitinib 6 and 12 mg demonstrated significantly greater ACR20 responses (primary endpoint) versus placebo (52.9% and 62.7% versus 31.8%, respectively). The selective TYK2 inhibitor was also superior regarding ACR50 and ACR70 improvement. Significant results were observed regardless of previous TNF inhibitor exposure or body weight (<90 kg vs ≥90 kg). Moreover, functional improvements (assessed using the Health Assessment Questionnaire–Disability Index) were significantly more pronounced in both deucravacitinib doses compared with placebo. Moreover, the treatment led to an increased quality of life and a resolution of enthesitis, while psoriasis-related and composite outcomes were improved compared with the placebo group.
The treatment was generally well tolerated with a safety profile consistent with that observed in the earlier psoriasis trial. “These results suggest that deucravacitinib may be a promising treatment for patients with active PsA and support its continued clinical development for this disease,” Prof. Mease concluded. Overall, it will be interesting to see whether TYK2 inhibition that selectively interferes with the PsA disease-associated IL-23/IL-17 axis will compare against pan-JAK or predominantly JAK1 inhibitors.
- Mease PJ, et al. Efficacy and safety of deucravacitinib (BMS-986165), an oral, selective tyrosine kinase 2 inhibitor, in patients with active psoriatic arthritis: results from a phase 2, randomized, double-blind placebo controlled trial. L03, ACR Convergence 2020, 5-9 Nov.
- Presented By
- Prof. Thomas MacDonald, University of Dundee, UK
- Presented By
- Dr Maria Cinta Cid, Hospital Clínic 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 Universitätsmedizin 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 Children’s Hospital, USA
- Presented By
- Ms Emily Sirotich, COVID‐19 Global Rheumatology Alliance Steering Committee and McMaster University, Canada
Posted on
Table of Contents: ACR 2020
Featured articles
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 – 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 – 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 – 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 – New Data
Bisphosphonate use: Asian American women have a smaller treatment benefit
Inflammatory disease as a risk factor for fractures
Best of the Posters
No progression of osteoarthritis with corticosteroid injections
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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