In a groundbreaking development, the one-year findings from the open-label extension of a phase III assessment have revealed Upadacitinib's (Janus kinase inhibitor) sustained efficiency and safety  in people having ankylosing spondylitis (AS) refractory to biologics. In the phase III SELECT-AXIS programs, Upadacitinib had previously demonstrated effectiveness and a favorable safety profile in AS sufferers.

The study, known as SELECT-AXIS 2, enrolled subjects aged 18 and above with active AS who met the modified New York criteria for AS and had an unsatisfactory response to biologic disease-modifying antirheumatic drugs (bDMARD-IR). Out of 420 patients randomly selected for the study, 366 individuals (comprising 181 in the continuous Upadacitinib group and 185 in the placebo to Upadacitinib group) successfully completed the 52-week treatment period.

For a period of fourteen weeks, participants were initially randomized to get either a double-blind 15 mg Upadacitinib once daily (QD) or a placebo. Those volunteers who completed this phase were then eligible to enter an open-label extension, where they received Upadacitinib 15 mg QD for up to two years.

Key findings:

• Efficacy Outcomes: At the 52-week mark, the continuous Upadacitinib group illustrated remarkable improvements with 66% attaining Assessment of SpondyloArthritis International Society response (ASAS40), 26% attaining Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease, and 57% attaining ASDAS low disease activity.
• Pain Reduction: Both total and nocturnal back pain showed substantial reduction, with changes from baseline at -4.5 and -4.3, and -4.6 and -4.4, respectively.
• Functional Improvement: The Bath Ankylosing Spondylitis Functional Index (BASFI) exhibited noteworthy improvement, with changes from baseline at -3.6 and -3.5.

Subgroup Assessment:

Consistent Results: Evaluation of subgroups, considering the distinction between lack of effectiveness and intolerance to bDMARDs, as well as prior exposure to tumor necrosis factor inhibitors (TNFi) versus interleukin-17 inhibitors, revealed consistent effectiveness when compared to the broader study population.

Safety Profile:

No New Safety Risks: The study reported no novel safety risks linked with the usage of Upadacitinib. Safety assessments were based on adverse events, and the drug's safety profile remained acceptable.

Hence, Upadacitinib 15 mg QD showcased sustained improvement up to 52 weeks in patients with AS refractory to biologic therapy. Efficacy results were generally similar in patients with both a lack of efficacy and intolerance to bDMARDs, as well as in those with prior exposure to TNFi versus IL-17i. This research marks a pivotal step forward in the treatment of AS, offering hope to individuals who have not responded adequately to previous biologic therapies. The findings support the continued exploration of Upadacitinib as a promising therapeutic option for this challenging condition.