Tofacitinib displays 'significantly greater' efficacy vs. placebo in ankylosing spondylitis
Tofacitinib 5 mg twice daily demonstrated “significantly greater” efficacy than placebo in adults with ankylosing spondylitis, according to researchers writing in the Annals of the Rheumatic Diseases.
“Tofacitinib is an oral Janus kinase (JAK) inhibitor that is being investigated for the treatment of adult patients with AS,” Atul Deodhar, MD, MRCP, of Oregon Health & Science University, in Portland, Oregon, and colleagues wrote. “JAK inhibitors directly bind to and modulate the intracellular catalytic activity of JAKs, which are essential enzymes in signaling pathways that mediate cytokine signaling for many innate and adaptive immune responses underlying the complex pathogenesis of AS.”
“In a phase 2, 16-week, randomized, placebo-controlled, dose-ranging study in patients with AS, tofacitinib 5mg and 10mg two times per day demonstrated greater efficacy versus placebo at week 12, with a safety profile consistent with that established in other indications,” they added. “These results suggested that JAK inhibition could present a new mechanism of action for treating AS.”
In a phase 3 study, Deodhar and colleagues aimed to assess the safety and efficacy of tofacitinib (Xeljanz, Pfizer) in adults with active AS. In this, randomized, double-blind, placebo-controlled trial, the researchers enrolled 269 participants who met the modified New York criteria for AS, with centrally read radiographs, and an inadequate response or intolerance to at least two NSAIDs. All participants were required to have active disease — defined as a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of fouror greater and a back pain score (BASDAI question two) at least four — at screening and baseline.
In the double-blind phase, participants were randomly assigned 1:1 to receive either 5 mg of tofacitinib twice daily or a placebo for 16 weeks. Then, in the open label phase, all participants received tofacitinib until week 48. Primary and secondary endpoints included improvement in Assessment of Spondyloarthritis International Society 20% (ASAS20) and 40% (ASAS40) responses at week 16. The researchers assessed safety throughout the trial.
According to the researchers, 56.4% of patients who received tofacitinib in the double-blind phase achieved ASAS20 response at week 16, compared with 29.4% in the placebo group (P < .0001). ASAS40 response rates were also significantly greater among patients in the tofacitinib group — 40.6% compared with 12.5% for placebo — during this time (p < .0001). The proportions of participants with adverse events up to week 16 were 54.9% and 51.5% for the tofacitinib and placebo groups, respectively. The rates for serious adverse events during this time were 1.5% and 0.7%, respectively.
Up to week 48, 2.3% of patients who received tofacitinib demonstrated adjudicated hepatic events, while 2.3% developed non-serious herpes zoster and 0.8% experienced a serious infection. Meanwhile, among those who switched from placebo to tofacitinib for the open-label phase, 1.5% demonstrated non-serious herpes zoster. There were no reported deaths, malignancies, major adverse cardiovascular events, thromboembolic events or opportunistic infections.
“Currently, the unmet need for treatment options is high in patients with AS, including a need for effective oral treatment options following NSAIDs and a need for additional mechanisms of action,” Deodhar and colleagues wrote. “If approved by regulatory agencies, tofacitinib could be one of a new class of drugs for use in AS, providing an additional treatment option for patients with this disease.”
“In this phase 3 study, patients with active AS and an [inadequate response or intolerance] to NSAIDs had a rapid, sustained and clinically meaningful response to tofacitinib 5mg two times per day, with no new potential safety risks identified,” they added. “This suggests a favorable benefit–risk balance in patients with active AS treated with tofacitinib.”