Researchers are assessing the oral JAK inhibitor tofacitinib as a treatment option for adults with ankylosing spondylitis (AS). Atul Deodhar, MD, is one of those researchers. In this video, he provides an overview of a primary analysis of a phase 3, randomized, double-blind, placebo-controlled study on tofacitinib in AS that he and his colleagues performed. He had presented the late-breaking abstract during the American College of Rheumatology’s (ACR) annual meeting, ACR Convergence.
Atul Deodhar, MD, is a professor of medicine in the Division of Arthritis and Rheumatic Diseases at Oregon Health & Science University’s School of Medicine in Portland where he is also medical director of rheumatology clinics.
- Deodhar A, Sliwinska-Stanczyk P, Xu H, et al. Tofacitinib for the treatment of adult patients with ankylosing spondylitis: primary analysis of a phase 3, randomized, double-blind, placebo-controlled study. Study presented at: American College of Rheumatology Convergence 2020; November 5-9, 2020; Virtual. Accessed November 11, 2020. https://acrabstracts.org/abstract/tofacitinib-for-the-treatment-of-adult-patients-with-ankylosing-spondylitis-primary-analysis-of-a-phase-3-randomized-double-blind-placebo-controlled-study/
- van der Heijde D, Deodhar A, Wei JC, et al. Tofacitinib in patients with ankylosing spondylitis: a phase II, 16-week, randomised, placebo-controlled, dose-ranging study. Ann Rheum Dis. 2017;76(8):1340-1347. doi:10.1136/annrheumdis-2016-210322 https://ard.bmj.com/content/76/8/1340
- Ward MM, Deodhar A, Gensler LS, et al. 2019 update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis. Arthritis Rheumatol. 2019;71(10):1599-1613. doi:10.1002/art.41042
Hello, my name is Atul Deodhar. I’m a professor of medicine at Oregon Health and Science University, Portland, Oregon.
At this year’s American College of Rheumatology Annual Meeting, I presented a late‑breaking abstract on tofacitinib for the treatment of ankylosing spondylitis, a phase III study. This was a randomized, double‑blind, placebo‑controlled study.
As you know, for ankylosing spondylitis, we do not have many oral drugs, apart from nonsteroidal anti‑inflammatory drugs. In patients with ankylosing spondylitis, after the nonsteroidal anti‑inflammatory drugs stopped working or if somebody cannot tolerate them because of gastrointestinal side effects, we straight go to biologics which are all injectable.
Tofacitinib has completed a phase II study in ankylosing spondylitis, and that study was successful, and that was published, and based on that, in fact, tofacitinib was already mentioned in the American College of Rheumatology, Spondylitis Association of America or SAA, and SPARTAN, which is Spondyloarthritis Research and Treatment Network, guidelines.
These are the 2019 treatment guidelines for axial spondyloarthritis. Tofacitinib, even though it is not yet approved by the FDA for the treatment of ankylosing spondylitis, the ACR, SAA, SPARTAN treatment guidelines already mentioned it. That was the third‑line agent after anti‑TNFs and IL‑17 drugs had failed or had inadequate response.
This was the phase III randomized, double‑blind, placebo‑controlled study of tofacitinib vs placebo. This was conducted in about 270 patients to evaluate the efficacy and safety of this drug in patients with active ankylosing spondylitis which is typically the disease in patients who are above the age of 18.
They had centrally read x-rays, so they had bilateral sacroiliitis, or at least sacroiliitis that can be classified as ankylosing spondylitis by the New York criteria.
The primary endpoint was ACR20 response at week 16. After week 16, patients who were on placebo went on to receive tofacitinib, 5 mg, twice a day. That is the dose. You’ll be able to see the details about the several secondary endpoints, which were controlled for type I error, below this presentation.
The primary endpoint was the ASAS20 response, and the ASAS20 response was 56.4% of patients on tofacitinib, 5 mg, BID compared to 29% of patients on placebo.
The study also met all of the global type I error‑controlled endpoints, as I said, and there are many of them, including the ASAS components, also efficacy over time up to week 16.
In the abstract presentation that I did, I presented the safety up to week 48, and there were no unusual adverse events. In fact, the safety profile was as expected, consistent with the known safety profile of tofacitinib as we found out in patients with rheumatoid arthritis or psoriatic arthritis. There were no new potential safety risks identified.
This was a successful study. As I said, this drug is not yet approved for the treatment of ankylosing spondylitis. JAK inhibitors is a new class of drugs now coming for the treatment of ankylosing spondylitis, which is certainly welcomed news. Thank you.