medwireNews: Three phase III trials have failed to demonstrate efficacy of the interleukin (IL)-12 and -23 inhibitor ustekinumab in patients with axial spondyloarthritis (axSpA).
As reported in Arthritis & Rheumatology, patients in all three trials were randomly assigned to receive subcutaneous ustekinumab 45 mg or 90 mg at weeks 0, 4, and 16, and every 12 weeks thereafter, or to receive placebo.
In the first trial, which included 346 tumor necrosis factor (TNF) inhibitor-naïve patients with radiographic axSpA and an inadequate response or intolerance to nonsteroidal anti-inflammatory drugs, ASAS40 response rates at week 24 were not significantly different among participants given ustekinumab 45 mg, ustekinumab 90 mg, or placebo, at 31.0%, 28.1%, and 28.4%, respectively.
Furthermore, patients receiving either dose of ustekinumab did not experience significant improvements in other endpoints, including ASAS20 response rates, BASFI score, and inactive disease according to an ASDAS-CRP score of less than 1.3 points, compared with those in the placebo group.
Because the primary and major secondary endpoints were not met in this trial, all three trials were terminated early, say Atul Deodhar (Oregon Health & Science University, Portland, USA) and co-investigators.
They add that not all patients in the other two trials had reached the 24-week timepoint when the studies were discontinued, and that efficacy analyses in these trials were limited. However, “no consistent trends of clinically relevant response were observed among primary and major secondary endpoints,” they report.
In the second trial, involving 213 patients with radiographic axSpA who were refractory to treatment with a TNF inhibitor, 19%, 27%, and 12% of patients in the ustekinumab 45 mg, ustekinumab 90 mg, and placebo groups, respectively, achieved an ASAS40 response at week 24.
And in the third trial of 250 patients with nonradiographic axSpA, a similar proportion of patients in the ustekinumab 45 mg, 90 mg, and placebo groups met the primary endpoint of an ASAS20 response (55%, 49%, and 48%, respectively).
Deodhar and colleagues say that the adverse events (AEs) observed in the three trials were “consistent with the known safety profile of ustekinumab.” A total of 39.7–48.3% of patients across the treatment arms experienced AEs, while serious AEs were reported in 0.8–4.8%.
Taken together, these findings suggest that “[a]dditional research is needed to better understand the pathogenic mechanisms and the cytokine pathways that manifest as axSpA,” conclude the investigators.
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