Risankizumab disappoints in ankylosing spondylitis trial
medwireNews: Patients with ankylosing spondylitis (AS) who are treated with the interleukin (IL)-23 inhibitor risankizumab do not experience clinically meaningful improvements in the signs and symptoms of disease, phase II study results suggest.
These findings suggest that “IL-23 may not be a relevant driver of disease pathogenesis and symptoms in AS,” despite a previously reported genetic association, say James Cheng-Chung Wei (Chung Shan Medical University, Taichung, Taiwan) and colleagues.
As reported in the Annals of the Rheumatic Diseases, the investigators randomly assigned 159 biologic-naïve patients with active AS to receive subcutaneous risankizumab at a single dose of 18 mg, or at a dose of 90 mg or 180 mg at baseline and weeks 8, 16, and 24, or to receive placebo.
“The doses selected were informed by a phase 1 study in psoriasis and included a 10-fold dose range of risankizumab,” explain Wei and team.
At week 12, the proportion of patients achieving at least a 40% improvement in Assessment of SpondyloArthritis International Society score (ASAS40) was 25%, 21%, and 15% in the risankizumab 18 mg, 90 mg, and 180 mg groups, respectively, compared with 18% for those given placebo.
The differences in ASAS40 response rates were not statistically significant between groups, and subgroup analyses by morning stiffness, geographic region, and C-reactive protein levels “did not reveal a higher ASAS40 response for any risankizumab group compared with placebo,” say the study authors.
They add that prolonging treatment with risankizumab 180 mg for up to 40 weeks among patients who did not receive an ASAS20 response at week 12 “did not substantially improve” ASAS40 response rates, and that the lack of efficacy was confirmed by most secondary endpoints, including changes in AS Disease Activity Score based on C-reactive protein (ASDAS-CRP) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI).
Rates of adverse events were comparable between patients given risankizumab and those in the placebo group, and the majority of these events were mild or moderate in severity.
“Findings of this study are in contrast to those reported for secukinumab, an IL-17A inhibitor that demonstrated efficacy in patients with AS,” write Wei and colleagues.
The researchers speculate that the absence of a loading dose in this study “might have potentially contributed to the negative results.” However, “because there was no convincing evidence for a dose response […] it is unlikely that a loading dose would have improved the treatment response in AS,” they say.
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