Xeljanz Shows Promise for Ankylosing Spondylitis in Phase 2 Trial

Ana Belo van Wijk, PhD avatar

by Ana Belo van Wijk, PhD |

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TNF inhibitors and risk

Xeljanz (tofacitinib) showed promising results for ankylosing spondylitis (AS) patients in a 16-week Phase 2 clinical trial. AS patients with active disease receiving Xeljanz treatment showed great improvement in symptoms and clinical disease profiles when compared to patients treated with placebo.

The study, “Tofacitinib in patients with ankylosing spondylitis: a phase II, 16-week, randomised, placebo-controlled, dose-ranging study,” was published in the journal Annals of the Rheumatic Diseases.

AS patients are normally treated with non-steroidal anti-inflammatory drugs aided by regular physical therapy. In prolonged active AS, patients receive tumor necrosis factor inhibitors (TNFi).

Xeljanz, developed by Pfizer, was approved in 2012 for rheumatoid arthritis by the U.S. Food and Drug Administration (FDA). The drug has been studied in several immune-mediated inflammatory diseases, such as rheumatoid arthritis, psoriasis, and ulcerative colitis.

Tofacitinib is described as an oral Janus kinase (JAK) inhibitor. JAK protein is involved in a cascade of reactions that are very important for inflammation. The drug inhibits this inflammation cascade leading to the relief of inflammatory symptoms. Also, the drug has been reported to decrease serum levels of the inflammatory factor TNF in patients.

The goal of the now completed Phase 2 clinical trial (NCT01786668) was to determine if Xeljanz was effective and safe for patients with active AS. In addition, researchers assessed which dose was the best in the treatment of AS patients.

The team recruited adult patients with active AS from several countries, including in Europe (Czech Republic, Germany, Hungary, Poland, Spain), Asia (Republic of Korea, Russia, Taiwan), the United States, and Canada.

In this first proof-of-concept clinical trial, 207 patients were randomly separated to receive either placebo or Xeljanz 2, 5 or 10 mg twice daily over 12 weeks. Follow-up continued for four weeks after the end of treatment.

The study’s primary objective was to analyze the patient’s response rate at week 12 through the Assessment of SpondyloArthritis International Society 20% improvement (ASAS20), which refers to a 20% improvement in symptoms after treatment.

Results showed that 80.8% of the patients receiving twice a day 5 mg of Xeljanz reached an ASAS20 response, which was significantly higher than in the placebo group, with 41.2%.

Treatment with 2 and 10 mg of Xeljanz, twice daily, also yielded a better response than in the placebo group; however, the difference was not statistically significant. Nevertheless, it indicates a trend in improvement in patients’ response rates after Xeljanz treatment.

The second goal of the study was to analyze how patients improved in treatment. Researchers measured disease activity, patient-reported outcomes, and MRI of sacroiliac joints and spine.

Overall, researchers found greater improvements in the Xeljanz 5 and 10 mg groups, compared with placebo, over 12 weeks of treatment across most endpoints assessed, with minimal clinical difference between the two doses.

Concerning safety, patients showed similar adverse events across the treatment groups, with no unexpected safety findings.

“Tofacitinib 5 and 10 mg twice daily demonstrated greater clinical efficacy versus placebo in reducing the signs, symptoms and spinal inflammation of AS in adults with active disease. The 12-week safety profile was similar to that reported for tofacitinib studies in other indications and no new safety signals or concerns were identified,” the researchers concluded.

The team believes that “JAK inhibition may present a new mode of action for managing AS and could add to the currently limited treatment options; however, other trials are needed to adequately evaluate the treatment effect of JAK inhibitors in AS.”