The oral selective JAK-1 inhibitor upadacitinib (Rinvoq) showed efficacy through 1 year among patients with ankylosing spondylitis in a phase II/III trial.
During the extension phase of a trial known as SELECT-AXIS 1, a 40% improvement on the criteria of the Assessment of SpondyloArthritis International Society (ASAS40) at week 64 was seen in 85% of patients in an as-observed (AO) analysis and by 72% in an analysis using non-responder imputation (NRI) for missing data, according to Atul Deodhar, MD, of Oregon Health & Science University in Portland, and colleagues.
Similarly, low disease activity on the Ankylosing Spondylitis Disease Activity Score (ASDAS), defined as a score below 2.1, was achieved by 84% (AO) and 70% (NRI) at week 64, the investigators reported online in Arthritis & Rheumatology.
Upadacitinib was designed to increase the selectivity for JAK1 rather than JAK2, JAK3, or tyrosine kinase 2, and has been approved for use in rheumatoid arthritis.
In the initial 14-week double-blind placebo-controlled phase of SELECT-AXIS 1, ASAS40 was observed in 54% (AO) and 52% (NRI) of patients with ankylosing spondylitis given upadacitinib, 15 mg once daily, compared with 25.5% of patients receiving placebo (P<0.001).
After 14 weeks, all patients received open-label upadacitinib, 15 mg daily. The current report is an interim analysis at week 64, when all patients had received at least a year of upadacitinib treatment. It is intended to continue through week 104.
The study is being conducted at 62 centers in 20 countries, and initially enrolled 187 patients with active disease who had inadequate responses or intolerance to two or more nonsteroidal anti-inflammatory drugs (NSAIDs). Concomitant treatment with stable doses of conventional disease-modifying antirheumatic drugs, NSAIDs, and oral glucocorticoids was permitted; patients with previous use of JAK inhibitors or biologic agents were excluded.
The NRI analysis considered any patient who prematurely stopped the study drug as a non-responder for all subsequent visits, and any patient with missing data from a specific visit was considered a non-responder for that visit.
A total of 178 patients completed the randomized 14-week phase of the trial and entered the extension phase, with 160 remaining on treatment at week 64.
Most patients were male, and mean age at baseline was 45 years. Symptom duration was 14.5 years, and mean ASDAS at baseline was 3.6. More than three-quarters were on concomitant NSAIDs.
At week 64, ASDAS inactive disease, defined as a score below 1.3, was observed in 42% (AO) and 34% (NRI), while ASAS partial remission was seen in 46% (AO) and 40% (NRI).
Among patients who initially received placebo and switched to upadacitinib after week 14, outcomes were comparable to those seen for patients on the active treatment throughout. For instance, ASAS40 responses at week 64 were seen in 81% (AO) and 70% (NRI), and ASDAS inactive disease was reported in 44% and 36%, respectively.
Consistent improvements also were seen on various secondary endpoints including quality of life, spinal mobility, back and nocturnal pain, and enthesitis.
For patients who were employed at baseline, changes on the Work Productivity and Activity Impairment score showed continued improvement after week 14, from -20.5 (95% CI -27.1 to -14) to -35.6 (95% CI -43.2 to -28) at week 52 in the continuous upadacitinib group and from -12.3 (95% CI -19.8 to -4.8) at week 14 to -27.7 (95% CI -35.4 to -20) at week 52 in the placebo/upadacitinib group.
The most common adverse events included nasopharyngitis, occurring at a rate of 15.6 per 100 patient-years, increased blood creatine phosphokinase (11.8 per 100 patient-years), and upper respiratory tract infections (10.9 per 100 patient-years).
The rate of serious adverse events was 5.9 per 100 patient-years, and the rate of adverse events leading to withdrawal was 6.3 per 100 patient-years. There were no serious infections, major cardiovascular events, venous thromboembolic events, or cases of renal dysfunction or gastrointestinal perforation.
Five cases of non-serious herpes zoster occurred in four patients, and two cases of moderate esophageal candidiasis occurred in one patient. Hepatic events primarily were transient asymptomatic elevations of liver enzymes that were mild-to-moderate in severity; no cases led to study withdrawal.
Sustained benefits have been observed for other agents in ankylosing spondylitis, such as tumor necrosis factor (TNF) inhibitors and interleukin (IL)-17 inhibitors. “Although no head-to-head trials are available, overall the efficacy of upadacitinib appears to be in line with that described with TNF and IL-17 inhibitor therapy in ankylosing spondylitis,” Deodhar and colleagues wrote.
In the ongoing extension study, additional efficacy and safety data will be obtained, along with imaging studies.
Limitations of the study were the open-label design of the extension study and the lack of an active comparator.
Last Updated July 02, 2021
The study was funded by AbbVie.
The authors reported financial relationships with AbbVie, Eli Lilly, Novartis, Pfizer, UCB, GlaxoSmithKline, Janssen, Boehringer Ingelheim, Bristol Myers Squibb, Amgen, Astellas, AstraZeneca, Bayer, Cyxone, Daiichi, Eisai, Galapagos, Gilead, Merck Regeneron, Roche, Sanofi, Takeda, Asahi-Kasei, Ayumi, Chugai, Kyowa Kirin, Ono, and Tanabe-Mitsubishi.