Tofacitinib brings rapid clinical response in ankylosing spondylitis
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Patients with ankylosing spondylitis demonstrated rapid clinical response to tofacitinib, which produced significantly greater efficacy than placebo, but with more adverse events, according to a speaker at ACR Convergence 2020.
“At week 16, the primary and type 1 error-controlled secondary efficacy endpoints were met, demonstrating significantly greater efficacy of tofacitinib 5 mg BID versus placebo in adult patients with active ankylosing spondylitis,” Atul Deodhar, MD, a professor of medicine at Oregon Health & Science University, in Portland, told attendees at the virtual meeting. “Patients had a rapid clinical response to tofacitinib.”
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To examine the safety and efficacy of tofacitinib (Xeljanz, Pfizer) in patients with AS, Deodhar and colleagues conducted a phase 3, randomized, double-blind, placebo-controlled study of 269 adults with active disease. All participants met the modified New York criteria, had centrally read radiographs and demonstrated an inadequate response or intolerance to at least two NSAIDs. In the 16-week double-blind phase, participants were randomized 1-to-1 to receive either 5 mg of tofacitinib twice daily or a placebo. After week 16, all participants received open label tofacitinib until week 48.
The researchers tested four separate families of efficacy endpoints, in hierarchical sequences to control for type 1 error. The first included ASAS20 response at week 16 — the study’s primary endpoint — and ASAS40 response at week 16 — the key secondary endpoint — as well as changes in ASDAS-CRP, hsCRP, ASQoL, SF36v2 PCS, BASMI–linear method and FACIT-F total score from baseline to week 16. The second family included change in baseline to week 16 in ASAS components — PtGA, total back pain, BASFI and inflammation. The third family was ASAS20 response over time, while the fourth was ASAS40 response over time. The researchers collected safety data up to weeks 16 and 48.
According to the researchers, 56.5% of patients who received tofacitinib achieved ASAS20 response at week 16, compared with 29.4% in the placebo group (P < .0001), while 40.6% of those in the tofacitinib group achieved the ASAS40 response during the same time, compared with 12.5% of those who received placebo (P < .0001). In addition, there were significant improvements with tofacitinib, compared with placebo, from baseline to week 16 in ASDAS-CRP, hsCRP, ASQoL, SF36v2 PCS, BASMI–linear method and FACIT-F total score.
Improvements in ASAS components were significantly greater with tofacitinib compared with placebo. The researchers also observed significant improvements with tofacitinib, compared with placebo, week 2 — the first post-baseline visit — in ASAS20 response, as well as at week 4 in ASAS40 response.
Adverse events up to week 16 were reported in 54.1% of participants receiving tofacitinib and in 51.5% of the placebo group, while serious and severe adverse events were each reported in 1.5% and 0% of participants, respectively. In all, three patients from the tofacitinib group, and one from the placebo group, discontinued due to adverse events. Safety trends remained similar up to week 48.
There were no cases of death, deep vein thrombosis, pulmonary embolism, arterial thromboembolism, gastrointestinal perforation, interstitial lung disease, major adverse cardiovascular events, malignancies or opportunistic infections up to week 48 in the tofacitinib group. Also among those treated with tofacitinib, adjudicated hepatic events were reported in one patient up to week 16, and in two patients up to week 48; one patient had meningitis up to week 16; and three patients had non-serious herpes zoster up to week 48.
There were no deaths or adverse events of special interest up to week 16 in the placebo group. Up to week 48, one patient who switched from placebo to tofacitinib demonstrated non-serious herpes zoster.
“The safety profile of tofacitinib in patients with ankylosing spondylitis was consistent with the known safety profile in patients with rheumatoid arthritis or psoriatic arthritis,” Deodhar said. “No new potential safety risks were identified in patients with ankylosing spondylitis.”
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