medwireNews: Results of a dose-ranging phase II trial support further investigation of the interleukin-23 inhibitor risankizumab for the treatment of psoriatic arthritis (PsA).
IL-23 “has been implicated in psoriatic skin lesions,” and “risankizumab has been shown to be highly effective in psoriasis,” lead author Philip Mease (Swedish Medical Center and University of Washington, Seattle, USA) told delegates at the 2017 ACR/ARHP Annual Meeting in San Diego, California, USA.
Mease and co-investigators randomly assigned 185 patients with active PsA to receive two, three, or five doses of risankizumab 150 mg, a single dose of risankizumab 75 mg, or placebo, over a 16-week period. A total of 172 participants completed the study; approximately 25% had undergone prior treatment with a tumor necrosis factor (TNF) inhibitor, and just over half were receiving methotrexate.
When the groups receiving three and five doses of risankizumab 150 mg were pooled in the primary endpoint analysis, 60% of patients achieved at least a 20% improvement in ACR criteria (ACR20) from baseline to week 16, compared with 36% of placebo-treated patients, a significant difference.
And all of the dose groups had significantly higher ACR20 response rates compared with the placebo arm, Mease told delegates, with rates ranging from 57% for the 42 patients given five 150 mg doses to 65% for the 20 patients who received a single 75 mg dose.
In a subgroup analysis of ACR20 responses based on prior treatment with TNF inhibitors, there was “some blunting” of the response to risankizumab among patients with prior exposure compared with TNF-naïve patients, noted Mease.
Risankizumab was also associated with significantly greater improvements in skin symptoms – as measured by the proportion of patients achieving a 75%, 90%, or 100% reduction in the Psoriasis Area and Severity Index (PASI) score – compared with placebo. In all, 67–75% of risankizumab-treated patients versus 10% of placebo-treated patients achieved a PASI 75 response, while 52–67% versus 10% and 33–56% versus 7% of patients achieved a PASI 90 or PASI 100 response, respectively.
The incidence of treatment-emergent adverse events (TEAEs) was comparable across the five treatment arms, with 52.4–69.2% of patients receiving risankizumab and 69.0% of those in the placebo group experiencing TEAEs. A corresponding 0–10.0% and 4.8% experienced serious TEAEs.
The most common TEAE was infection, reported in 30.0–41.0% of risankizumab-treated patients and 28.6% of patients in the placebo arm, and infections occurred most frequently in the upper respiratory tract.
“The safety and tolerability profile was consistent with observations from previous risankizumab trials,” said Mease.
He announced that risankizumab “is being taken forward into phase III [trials],” and noted that the pending phase II clinical and radiographic data at the 24-week follow-up are needed “so that we can best judge what will be the best doses to carry forward.”
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