Guselkumab shows promise for PsA
medwireNews: Findings from the DISCOVER-1 and DISCOVER-2 trials presented at the 2019 ACR/ARP Annual Meeting in Atlanta, Georgia, USA, suggest that the interleukin (IL)-23 inhibitor guselkumab may be a promising treatment option for people with psoriatic arthritis (PsA).
Following these results, there will be “an application for approval of guselkumab for the treatment of psoriatic arthritis, and we anticipate that [the approval] will follow in due course,” DISCOVER-2 lead investigator Philip Mease (Swedish Medical Center and University of Washington, Seattle, USA) told medwireNews.
In both phase III trials, adult patients with active PsA despite standard therapy were randomly assigned to receive subcutaneous guselkumab 100 mg every 4 weeks, guselkumab 100 mg every 8 weeks (after 100 mg loading doses at weeks 0 and 4), or placebo.
In DISCOVER-1, which involved 381 patients who were either biologic-naïve or had previously been treated with up to two tumor necrosis factor (TNF) inhibitors, ACR20 response rates at week 24 were significantly higher among patients treated with guselkumab every 4 weeks or every 8 weeks than among those given placebo, at 59.4% and 52.0% versus 22.2%, respectively.
Presenting author Atul Deodhar (Oregon Health & Science University, Portland, USA) said that consistent responses were seen regardless of prior TNF inhibitor use. Specifically, among the TNF inhibitor-experienced patients – 31% of the total study population – ACR20 response rates at week 24 were 57.9%, 56.1%, and 17.9% in the guselkumab every 4 weeks, guselkumab every 8 weeks, and placebo groups, respectively. The corresponding rates for the TNF inhibitor-naïve patients were 60.0%, 50.0%, and 24.1%.
The DISCOVER-2 trial was larger than DISCOVER-1 (n=739), involved only biologic-naïve patients, and included structural damage endpoints.
Philip Mease said that the findings from DISCOVER-2 “are very consistent with what was shown in DISCOVER-1.”
Indeed, a significantly greater proportion of patients treated with guselkumab every 4 weeks or every 8 weeks versus placebo achieved an ACR20 response at week 24, at rates of 63.7% and 64.1% versus 32.9%, respectively.
Mease said that ACR50 and ACR70 response rates were also significantly greater among patients treated with guselkumab versus placebo. Average changes in mTSS score – a measure of structural damage progression – were significantly smaller for participants treated with guselkumab every 4 weeks versus placebo.
Rates of enthesitis and dactylitis were assessed using pooled data from DISCOVER-1 and DISCOVER-2. A total of 63.5% and 59.4% of patients given guselkumab every 4 weeks and every 8 weeks, respectively, achieved complete resolution of dactylitis, compared with just 42.2% of those in the placebo group. A corresponding 44.9%, 49.6%, and 29.4% experienced resolution of enthesitis.
“Dactylitis and enthesitis are unique characteristics of psoriatic arthritis, and it is of great interest for us to see how these clinical domains respond to treatment,” because they do not respond well to other treatments such as methotrexate, explained Mease.
“Clearly in these domains, interleukin-23 inhibition is highly effective,” he added.
Overall, guselkumab had a favorable safety profile in the DISCOVER-1 and -2 studies, which the investigators say was consistent with the established profile demonstrated previously in patients with psoriasis.
Looking to the future, Mease thinks that further research should address persistence of response to guselkumab, as well as treat-to-target strategies using the agent, and treatment tapering.
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