Upadacitinib Shows Positive Results in Clinical Trials for AS, nr-axSpA Advances

Upadacitinib, a selective and reversible Janus kinase (JAK) inhibitor, has demonstrated superior efficacy over placebo in 2 phase 3 clinical trials among adult patients with active ankylosing spondylitis (AS) or nonradiographic axial spondyloarthritis (nr-axSpA).

The SELECT-AXIS 1 trial was a randomized, multicenter, double-blind, placebo-controlled, 2-period, parallel-group, phase 2/3 study. The trial enrolled adults patients in 62 sites in 20 countries with active AS who also fulfilled modified New York criteria, were naïve to biological disease-modifying antirheumatic drugs (bDMARDS), and had inadequate response to at least 2 nonsteroidal anti-inflammatory drugs (NSAIDS) or who were intolerant to NSAIDS or for whom NSAIDS were contraindicated.

At week 14, 52% of the adult patients with AS treated with upadacitinib 15 mg once daily had an Assessment of SpondyloArthritis international Society (ASAS) 40 response, compared to 26% of patients in the placebo group (48 of 93 patients vs 24 of 94 patients; p=0.0003; treatment difference 26% [95% CI 13–40]).

SELECT-AXIS 2 was the first trial to evaluate the efficacy and safety of upadacitinib in adult patients with nr-axSpA. Adult patients with nr-axSpA were randomized to upadacitinib 15 mg once daily (n=156) or placebo (n=157). Among the upadacitinib group, 42% achieved Ankylosing Spondylitis Disease Activity Score (ASDAS) Low Disease Activity vs 18% who received placebo (p<0.0001).

Upadacitinib 15 mg once daily showed sustained and consistent efficacy over 1 year in these clinical trials and showed similar efficacy among patients who had been on placebo but were switched to upadacitinib after week 14 and those who received upadacitinib throughout the trial.

Adverse events in SELECT-AXIS 1 were reported in 58 (62%) of 93 patients in the upadacitinib group vs 52 (55%) of 94 in the placebo group. The most common adverse event in the upadacitinib group was increased creatine phosphokinase (8 [9%] of 93 patients in the upadacitinib group vs 2 [2%] of 94 the placebo group). There were no serious infections, herpes zoster, malignancy, venous thromboembolic events, or deaths reported. One serious adverse event occurred in each group.

Safety data for SELECT-AXIS 2 were consistent with those of SELECT-AXIS 1 and with the known safety profile of upadacitinib, with no new risks identified. Through week 14, the most common adverse events (≥ 3 percent of patients) reported were headache, COVID-19, nasopharyngitis and nausea.

Upadacitinib has not been approved for use in nr-axSpA but is approved by the U.S. Food and Drug Administration for adults with moderately to severely active rheumatoid arthritis. The European Commission has approved upadacitinib for adults with adults with active ankylosing spondylitis as well as those with moderate to severe active rheumatoid arthritis and active psoriatic arthritis.

Phase 3 trials of upadacitinib in rheumatoid arthritis, atopic dermatitis, psoriatic arthritis, axial spondyloarthritis, Crohn disease, ulcerative colitis, giant cell arteritis and Takayasu arteritis are ongoing.

REFERENCES

Deodhar A, van der Heijde D, Sieper J, et al. Safety and efficacy of upadacitinib in patients with active ankylosing spondylitis and an inadequate response to nonsteroidal antiinflammatory drug therapy: one-year results of a double-blind, placebo-controlled study and open-label extension. Arthritis Rheumatol. July 1, 2021. Online ahead of print.  doi: 10.1002/art.41911

AbbVie's upadacitinib (RINVOQ®) met primary and most ranked secondary endpoints in phase 3 study for non-radiographic axial spondyloarthritis. [press release]. AbbVie. October 7, 2021. https://www.prnewswire.com/news-releases/abbvies-upadacitinib-rinvoq-met-primary-and-most-ranked-secondary-endpoints-in-phase-3-study-for-non-radiographic-axial-spondyloarthritis-301395109.html