Rinvoq (upadacitinib), an oral therapy recently approved for rheumatoid arthritis, was effective in treating adults with active ankylosing spondylitis (AS) who failed to respond to or are not eligible for non-steroidal anti-inflammatory drugs (NSAIDs), a Phase 2/3 trial shows.
After 14 weeks of treatment, taking daily pills of Rinvoq was found to ease disease symptoms in twice as many patients as a placebo. Other benefits included a greater proportion of individuals with both reduced disease activity and better quality of life.
The study, “Efficacy and Safety of Upadacitinib in a Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase 2/3 Clinical Study of Patients with Active Ankylosing Spondylitis,” was presented at the 2019 American College of Rheumatology (ACR)/Association for Rheumatology Professionals (ARP) Annual Meeting, held recently in Atlanta. A detailed report was published in the journal The Lancet.
Rinvoq is used to reduce joint pain, swelling, and stiffness in adults with moderate-to-severe rheumatoid arthritis who had an inadequate response or intolerance to methotrexate. Sold by Abbvie, Rinvoq was approved in August 2019 by the U.S. Food and Drug Administration. In the E.U., the Committee for Medicinal Products for Human Use, an arm of the European Medicines Agency, recently recommended marketing authorization for the medication.
Available in 15 mg prolonged-release tablets, the therapy is taken once daily. The active compound, upadacitinib, is a selective and reversible Janus kinase (JAK) inhibitor that works as an immunosuppressant by targeting the cellular enzyme JAK.
Given its ability to suppress the immune system, Abbvie also is investigating Rinvoq as a potential treatment for other inflammatory diseases, including AS.
“Unlike rheumatoid arthritis or psoriatic arthritis, therapy options for axial spondyloarthritis are limited because conventional synthetic [non-biologic] disease-modifying antirheumatic drugs [DMARDs] or glucocorticoids are not effective for the treatment of axial (spine) symptoms,” the researchers said. Axial spondyloarthritis includes AS, when joint damage is visible through X-rays, and non-radiographic axial spondyloarthritis — when such damage is not visible on radiographs.
To address this unmet need, Abbvie is running SELECT-Axis 1 (NCT03178487), a Phase 2/3 trial evaluating the safety and efficacy of Rinvoq in adults with active AS. Participants were not treated with DMARDs, and responded poorly or are intolerant or contraindicated to receive NSAIDs.
The study enrolled 187 patients across 20 countries. Participants were randomly assigned to receive 15 mg of Rinvoq or placebo daily. Among the participants, the mean age was 45.4 years and symptom duration was 14.4 years.
The trial consists of two parts. The first part, completed in January 2019, comprised a double-blind treatment period of 14 weeks. The second part is an open-label extension period designed to evaluate the long-term safety, tolerability, and efficacy of Rinvoq in participants who completed the first part.
At the ACR/ARP annual meeting, the researchers presented the results of the study’s first part, completed by nearly all participants (178). The results showed that significantly more patients taking Rinvoq (52%) experienced an improvement of at least 40% in their health condition or function, and relief in pain or inflammation compared with the placebo group (26%) at week 14. Improvement was measured by the ASAS40 Assessment in Ankylosing Spondylitis.
Other multiple secondary measures of efficacy also favored Rinvoq. These included the proportion of patients in partial remission and those with a reduction in disease activity as measured by ASAS and the Bath AS Disease Activity Index, or BASDAI. Improvement in daily life abilities, as measured by the BASFI, and the results of spinal MRI scans also were evaluated.
Rinvoq’s safety profile was consistent with that of previous studies, with no new safety findings observed. Adverse events were reported by 62% of participants taking Rinvoq and 55% of those on placebo.
The most common side effect associated with Rinvoq was elevated levels of creatine phosphokinase, a marker of tissue damage. No serious infections, cancers,or deaths were reported. The proportions of patients with adverse events leading to discontinuation was similar with Rinvoq (2.2%) and placebo (3.2%).
“Overall, these results support the further investigation of upadacitinib [Rinvoq] for the treatment of axial spondyloarthritis,” the scientists said.
“Apart from biologics, there are limited options available for patients who have an inadequate response or contraindication to NSAIDs,” Désirée van der Heijde, MD, PhD, the study’s lead investigator and a professor at Leiden University Medical Center, the Netherlands, said in a press release.
“The results of this study highlight the potential of Rinvoq as an additional treatment option for patients living with ankylosing spondylitis, ” she added.