Phase 3 Study Results Indicate Tofacitinib Is Safe and Effective in Treating Active Ankylosing Spondylitis

Researchers assessed the efficacy and safety of tofacitinib in adult patients with active ankylosing spondylitis.

Tofacitinib demonstrated greater efficacy compared with placebo in patients with active ankylosing spondylitis (AS) with an inadequate response to nonsteroidal anti-inflammatory drugs (NSAIDs), according to phase 3 study results published in Annals of the Rheumatic Diseases.

For AS, NSAIDs are the first-line treatment, followed by biologic disease-modifying antirheumatic drugs (bDMARDs). Given that many patients have an inadequate response or intolerance to NSAIDs and that bDMARDs are administered parenterally, there is an unmet need for alternative treatment options. Tofacitinib is an oral Janus kinase (JAK) inhibitor that is approved for use in patients with rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, and juvenile idiopathic arthritis.

The current phase 3 study examined the efficacy and safety of tofacitinib use in patients with active AS.

The double-blind, placebo-controlled study ( Identifier: NCT03502616) was conducted at 75 centers in 14 countries between June 2018 and August 2020. Patients aged 18 and older were included in the analysis if they had active AS, fulfilled the New York criteria (based on central reading of the radiograph of the sacroiliac joint), and had an inadequate response or intolerance to 2 or more NSAIDs. Patients were randomly assigned 1:1 to receive 5 mg tofacitinib twice per day or placebo during the double-blind phase (weeks 0 to 16). During the open-label phase (weeks 16 to 48), all patients received 5 mg tofacitinib twice per day.

The primary study endpoint was the Assessment in Ankylosing Spondylitis International Society response criteria for at least 20% improvement (ASAS20) at week 16. The secondary endpoint was the ASAS40 response (≥40% improvement) at week 16. Safety was assessed throughout the study.

A total of 269 patients (133 in the treatment group and 136 in the placebo group) were included in the analysis. The ASAS20 response rate at week 16 was significantly greater with tofacitinib vs placebo (56.4% vs 29.4%, respectively; P <.0001). The ASAS40 response rate at week 16 was also significantly greater with tofacitinib vs placebo (40.6% vs 12.5%, respectively; P <.0001).

The efficacy of tofacitinib in the treatment group was sustained from week 16 through week 48. In the placebo group that received tofacitinib from weeks 16 to 48, clinical response improved between weeks 16 and 24 and was sustained through week 48.

In the tofacitinib and the placebo groups, adverse event rates were 54.9% and 51.5%, respectively; serious adverse event rates were 1.5% and 0.7%, respectively. There were no deaths, malignancies, major adverse cardiovascular events, thromboembolic events, or opportunistic infections.

Limitations of the study included the relatively small sample size and short follow-up period. The study also lacked the use of imaging such as magnetic resonance imaging (MRI) to evaluate improvements.

Researchers concluded, “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. 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.”

Disclosure: This research was supported by Pfizer Inc. Please see the original reference for a full list of authors’ disclosures.


Deodhar A, Sliwinska-Stanczyk P, Xu H, et al. Tofacitinib for the treatment of ankylosing spondylitis: a phase III, randomized, double-blind, placebo-controlled study. Ann Rheum Dis. Published online April 27, 2021. doi:10.1136/annrheumdis-2020-219601