Patients with active ankylosing spondylitis (AS) experienced rapid clinical response to the oral Janus kinase (JAK) inhibitor tofacitinib (Xeljanz) in a phase 3, randomized, double-blind, placebo-controlled study.
Tofacitinib was significantly more effective than placebo at primary and secondary endpoints. Adverse events were more frequent with tofacitinib than with placebo, but there were no new safety risks.
Results were presented on Monday at ACR Convergence 2020 by Atul Deodhar, MD, medical director of rheumatology clinics at the Oregon Health and Science University, Portland, Oregon.
At week 16, 56.4% of patients who received tofacitinib met ASAS20 criteria (Assessment of Ankylosing Spondylitis, a validated measure of 20% improvement), compared to 29.4% in the placebo group (P < .0001). The percentage of ASAS40 responders (40% improvement) at week 16 was also significantly greater with tofacitinib (40.6%) than placebo (12.5%) (P < .0001).
The trial, sponsored by Pfizer, enrolled 269 adults with active AS who had had a poor response to or were intolerant of at least two nonsteroidal anti-inflammatory drugs. Most in the active treatment and placebo groups were men (about 85%); the average age was 41 years. Most (77%) had no prior exposure to biologic disease-modifying antirheumatic drugs (DMARDs).
"Symptom duration was about 13 years," Deodhar said.
In the 4-month double-blind phase, patients were randomly assigned in a 1:1 ratio to receive either tofacitinib 5 mg twice a day or placebo. After 16 weeks, all patients received open-label tofacitinib until week 48.
Safety was a secondary endpoint, Deodhar said.
In the tofacitinib group, 72 patients (54.1%) experienced adverse events (AEs), compared to 70 patients in the placebo group (51.5%). Two patients in the treatment group experienced severe AEs; none in the placebo group did so. In the treatment group, three patients left the trial because of AEs; in the placebo group, one patient did so.
The most common AEs were upper respiratory tract infection and nasopharyngitis.
"There were no unexpected side effects in this study," Deodhar said. He noted that the risks were similar to known risks for those taking the drug for rheumatoid arthritis and psoriatic arthritis.
With tofacitinib there were no deaths, thromboembolic events, malignancies, major cardiac events, or gastrointestinal perforation. By week 48, three patients in the tofacitinib group had had nonserious herpes zoster, vs one in the placebo group.
Deodhar said, "There's a lot of hand-wringing" about why a JAK inhibitor would be effective for AS, inasmuch as it does not target the tumor necrosis factor (TNF) pathway or interleukin-17 (IL-17).
"Somehow, JAK inhibitor drugs are downstream, affecting several cytokines that we know are important in the pathogenesis and the phenotypic expression of the disease," he said.
Sonali Khandelwal, MD, at Rush University Medical Center, Chicago, Illinois, who did not take part in the research, told Medscape Medical News that tofacitinib holds promise as a much-needed option.
"JAK inhibitors have been used with success in RA, and it is reassuring to see these phase 3 data for AS," especially for those patients whose disease was not well controlled with other approved agents, she said.
She added that oral administration is a plus for patients.
"AS, like all other chronic rheumatologic conditions, has no cure," Khandelwal noted. "The advent of biologics has changed the course of these conditions, but not one drug works for everyone."
She said it would be helpful if future trials were to compare the safety and efficacy of tofacitinib to those of biologics that have already been approved for AS, such as anti-TNF agents and IL-17 antagonists.
The study was sponsored by Pfizer. Deodhar reported relationships with Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, UCB, AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Janssen, Galapagos, and Gilead. Khandelwal has disclosed no relevant financial relationships.
American College of Rheumatology (ACR) 2020 Annual Meeting: Abstract L11. Presented November 9, 2020.
Marcia Frellick is a freelance journalist based in Chicago. She has previously written for the Chicago Tribune and Nurse.com and was an editor at the Chicago Sun-Times, the Cincinnati Enquirer, and the St. Cloud (Minnesota) Times. Follow her on Twitter at @mfrellick.
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Cite this: Tofacitinib Effective for Ankylosing Spondylitis in Phase 3 - Medscape - Nov 10, 2020.