According to Atul Deodhar, MD, MRCP, of Oregon Health & Science University, in Portland, Oregon, and colleagues, “Tofacitinib, an oral Janus kinase (JAK) inhibitor, being investigated in order to treat adult patients with ankylosing spondylitis.”
Janus kinase inhibitors specifically directly bind to and modulate the intracellular catalytic activity of JAKs, which are essential enzymes in order to signal pathways, mediate cytokine signaling for multiple innate and adaptive immune responses underlying the complex pathogenesis of ankylosing spondylitis.
The tofacitinib 5 mg twice daily demonstrated significantly greater efficacy than placebo in adult patients with ankylosing spondylitis, according to researchers writing in the Annals of the Rheumatic Diseases.
Researchers suggested, “In a Phase-II, sixteen week, randomized, placebo-controlled, dose ranging study in patients with the ankylosing spondylitis, tofacitinib 5 mg and 10 mg twice daily demonstrated greater efficacy vs placebo at the week 12, with a safety profile consistent with that established in other indications. These outcomes suggested that Janus kinase inhibition could present a new function for the treatment of ankylosing spondylitis.”
In a Phase-III study, Deodhar and colleagues aimed to assess the safety and efficacy of tofacitinib (xeljanz 5 mg) in adults with active ankylosing spondylitis. In this, randomized, double-blind, placebo-controlled trial, the researchers enrolled a total of 269 candidates who met the modified New York criteria for the ankylosing spondylitis, with centrally read radiographs, and an inadequate response or not tolerance to minimum a couple of NSAIDs.
All the enrolled candidates were needed to have active disease, defined as a BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) score of 4 or greater and a back pain score of at least four, at screening and baseline.
In the double-blind phase, candidates 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 the participants were given tofacitinib until week 48.
Primary endpoints and secondary endpoints included improvement in Assessment of the Spondyloarthritis International Society 20% (ASAS20) and 40% (ASAS40) responses at week 16. The researchers specifically evaluated the safety throughout the trial.
According to the researchers, 56.4% of patients who were given tofacitinib in the double-blind phase achieved Spondyloarthritis International Society 20% response at week 16, compared with 29.4% in the placebo group (P < .0001). Spondyloarthritis International Society 40% response rates were also greater among patients in the tofacitinib population, 40.6% compared with 12.5% for placebo, during this time (p < .0001).
Proportions of the participants with adverse events up to week 16 were noted as 54.9% & 51.5% for the tofacitinib 5 mg tablet and placebo groups, respectively. The rates for serious adverse events during this time were noted as 1.5% & 0.7%, respectively.
Up to week 48, 2.3% of patients who were given tofacitinib noted adjudicated hepatic events, while 2.3% noticed non-serious herpes zoster and 0.8% had a serious infection.
Meanwhile, among all those who switched from placebo to tofacitinib for the open-label phase, 1.5% noted non-serious herpes zoster. There were no reported deaths, malignancies, major adverse cardiovascular events, thromboembolic events or opportunistic infections.
Deodhar and colleagues wrote, “Currently, the unmet requirement for the treatment options is greater in patients with ankylosing spondylitis, including a requirement for the effective oral treatment options after NSAIDs and a requirement for additional mechanisms of action.”
“In case approved by the regulatory agencies, tofacitinib could be one of a new class of drugs for the treatment of ankylosing spondylitis, providing an additional treatment option for patients with this disease,” they added.
The average wholesaler tofacitinib cost for a supply of 60 tablets is around ₹ 24,900/ Bottle.