Tofacitinib for the treatment of ankylosing spondylitis: a phase III, randomised, double-blind, placebo-controlled study

Abstract

ObjectiveTo assess the efficacy/safety of tofacitinib in adult patients with active ankylosing spondylitis (AS).MethodsThis phase III, randomised, double-blind, placebo-controlled study enrolled patients aged ≥18 years diagnosed with active AS, meeting the modified New York criteria, with centrally read radiographs, and an inadequate response or intolerance to ≥2 non-steroidal anti-inflammatory drugs. Patients were randomised 1:1 to receive tofacitinib 5 mg two times per day or placebo for 16 weeks. After week 16, all patients received open-label tofacitinib until week 48. The primary and key secondary endpoints were Assessment of SpondyloArthritis international Society ≥20% improvement (ASAS20) and ≥40% improvement (ASAS40) responses, respectively, at week 16. Safety was assessed throughout.Results269 patients were randomised and treated: tofacitinib, n=133; placebo, n=136. At week 16, the ASAS20 response rate was significantly (p<0.0001) greater with tofacitinib (56.4%, 75 of 133) versus placebo (29.4%, 40 of 136), and the ASAS40 response rate was significantly (p<0.0001) greater with tofacitinib (40.6%, 54 of 133) versus placebo (12.5%, 17 of 136). Up to week 16, with tofacitinib and placebo, respectively, 73 of 133 (54.9%) and 70 of 136 (51.5%) patients had adverse events; 2 of 133 (1.5%) and 1 of 136 (0.7%) had serious adverse events. Up to week 48, with tofacitinib, 3 of 133 (2.3%) patients had adjudicated hepatic events, 3 of 133 (2.3%) had non-serious herpes zoster, and 1 of 133 (0.8%) had a serious infection; with placebo→tofacitinib, 2 (1.5%) patients had non-serious herpes zoster. There were no deaths, malignancies, major adverse cardiovascular events, thromboembolic events or opportunistic infections.ConclusionsIn adults with active AS, tofacitinib demonstrated significantly greater efficacy versus placebo. No new potential safety risks were identified.Trial registration numberNCT03502616

Monocytes and Macrophages in Spondyloarthritis: Functional Roles and Effects of Current Therapies

“…Since JAK receptors are also involved in different proinflammatory signalling pathways observed in the pathogenesis of SpA, JAKi are promising therapeutic options [156]. In fact, Tofacitinib, a JAK1 and JAK3 inhibitor, is a drug already approved in PsA [157] and with promising results in a phase III trial in AS [158]. However, the effect of Tofacitinib on SpA monocyte/macrophages activation is still unknown and further research is needed in this context.…”

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“…Adverse events were similar across treatment groups [ 34 ]. This trial was next completed by a phase-three study enrolling patients with AS and an inadequate response to at least two NSAIDs [ 35 ]. Patients were randomized to receive tofacitinib 5 mg twice daily, or placebo, for 16 weeks, followed by an open-label tofacitinib period until week 48.…”

Responding to and Driving Change in Rheumatology: Report from the 12th International Immunology Summit 2021

“…SpA and PsA are both complex diseases that can be difficult to treat. For patients with radiographical axial SpA or ankylosing spondylitis (AS), non-head-to-head clinical trials show that agents with varying mechanisms of action, including TNF inhibitors [ 24 – 27 ], IL-17A inhibitors [ 28 , 29 ] and Janus kinase (JAK) inhibitors [ 30 , 31 ], have broadly similar efficacy, with treatment response rates of 41–69% after 12–16 weeks of treatment (based on a 20% improvement in Assessment Of Spondyloarthritis International Society [ASAS20] response criteria) (Fig. 3 ).…”