12/17/2021
The U.S. FDA has approved a new medication to treat ankylosing spondylitis (AS) – tofacitinib, known as Xeljanz or Xeljanz XR.
Tofacitinib is the first Janus kinase (JAK) inhibitor, or JAKi, to receive approval to treat adults with active AS. The medication has been cleared for use in those who cannot tolerate or do not respond adequately to TNF inhibitors (TNFi), according to drugmaker Pfizer.1
As detailed in a comprehensive, recent Spondylitis Plus article, JAKi are the latest class of synthetic (non-biologic) drugs that have been proven remarkably effective in clinical trials in treating multiple forms of arthritis, including AS and psoriatic arthritis (PsA).2
Not only does tofacitinib’s approval usher in a new treatment approach for AS patients, but it is also the first new pill since NSAIDs were indicated for the disease.
“We are proud to offer Xeljanz, a treatment option for ankylosing spondylitis that does not require an injection or an infusion, to treat this debilitating and chronic immuno-inflammatory disease,” said Mike Gladstone, Global President, Inflammation & Immunology, Pfizer.
In a phase III clinical trial involving 269 adults with AS, 56% of patients who received 5mg of tofacitinib twice daily saw an improvement in symptoms of 20% or more as measured by the Assessment of Spondyloarthritis International Society criteria (ASAS 20) after 16 weeks of treatment, compared with 29% of those who received a placebo – a significant difference. A 40% improvement (according to ASAS 40) was seen in 41% of those treated with the medication, as opposed to 13% in the placebo group.4,5
A rapid clinical response was also observed among those treated with tofacitinib, as early as week two.2
Patients treated with tofacitinib also showed significant improvements in other clinical measures and outcomes related to disease activity, mobility, function, fatigue, and health-related quality of life, compared with the placebo group.
“Despite the tremendous advances within the last two decades, up to 40% of people living with AS in the U.S. do not show adequate response to the current treatments, including the use of biologics,” said rheumatologists Nurullah Akkoç, MD and Muhammad Asim Khan, MD, the authors of the Spondylitis Plus article linked above. “Therefore, the very recent approval of Tofacitinib by the FDA provides not only an additional treatment option for such patients but also for those who may favor taking tablets rather than getting injections or intravenous infusions.”
In September, the FDA issued a new drug safety report for JAKi, after a review of a large, randomized safety clinical trial of tofacitinib that included RA patients aged 50 or older who had a preexisting cardiovascular risk factor. The trial results showed that treatment with either 5mg or 10mg twice-daily doses of tofacitinib, compared with TNFi, was associated with an increased risk of heart attack, stroke, lymphoma, and lung cancer, among other adverse events.3
Based on that data, the FDA has required new boxed warnings for tofacitinib and two other JAKi, baricitinib, and upadacitinib. The FDA also recommended limiting the use of these drugs to patients with an inadequate response to or intolerance of TNFi.
“We are unsure whether these safety concerns and FDA warnings would also apply to patients with axial spondyloarthritis (axSpA), who are more likely to be younger than a typical RA population. Moreover, not everyone in the axSpA population is expected to have a cardiovascular risk factor, like those in the tofacitinib safety study sample,” wrote Drs. Khan and Akkoç in the Spondylitis Plus article linked in this article.
Experts believe further JAKi approvals could come in 2022.
1. U.S. FDA Approves Pfizer’s XELJANZ® (tofacitinib) for the Treatment of Active Ankylosing Spondylitis | Pfizer
2. JAK Inhibitors: A New Treatment Option on the Horizon for Spondyloarthritis – SAA (spondylitis.org)
3. FDA Posts Warnings on JAK Inhibitors Over Heart Safety, Other Health Risks – SAA (spondylitis.org)
4. The ASAS Response Criteria (ASAS 20) is defined as an improvement of at least 20%, and an absolute improvement of at least 10 units on a 0-100 scale, in at least three of the following domains: Patient Global Assessment, Pain Assessment, Function (BASFI), and Inflammation (last 2 questions of BASDAI).
5. The ASAS Response Criteria (ASAS 40) is defined as an improvement of at least 40%, and an absolute improvement of at least 10 units on a 0-100 scale, in at least three of the following domains: Patient Global Assessment, Pain Assessment, Function (BASFI), and Inflammation (last 2 questions of BASDAI).
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