medwireNews: The SELECT-PsA-1 and SELECT-PsA-2 trials presented at the EULAR 2020 E-Congress have demonstrated that the Janus kinase (JAK)-1 selective inhibitor upadacitinib may be a promising treatment option for psoriatic arthritis (PsA) patients with and without prior exposure to biologic agents.
SELECT-PsA-1, presented by Iain McInnes (University of Glasgow, UK), included 1704 patients with active PsA and an inadequate response or intolerance to at least one nonbiologic DMARD who were randomly assigned to receive upadacitinib 15 mg or 30 mg once daily, placebo, or the active comparator adalimumab at a dose of 40 mg every other week.
With over 400 participants per arm, “this makes for a very sizeable clinical trial indeed,” said McInnes.
At the 12-week follow-up, ACR20 response rates were significantly higher among patients given upadacitinib 15 mg (n=429) or 30 mg (n=423) compared with those given placebo (n=423), at 71% and 79% versus 36%, respectively. The ACR20 response rate in the adalimumab arm (n=429) was 65%.
McInnes said that there was noninferiority between both doses of upadacitinib and adalimumab, while the higher dose of upadacitinib resulted in significantly higher ACR20 response rates than adalimumab. The investigators observed a similar overall pattern of results for ACR50 and ACR70 response rates, and McInnes reported that a “very satisfactory” proportion of upadacitinib-treated patients experienced resolution of enthesitis and dactylitis.
The SELECT-PsA-2 trial, involving patients with active PsA and an inadequate response or intolerance to at least one biologic agent, also demonstrated significant benefits with upadacitinib over placebo.
Lead investigator Philip Mease (Swedish Medical Center and University of Washington, Seattle, USA) reported that ACR20 response rates at week 12 were significantly higher among the 211 patients randomly assigned to receive upadacitinib 15 mg/day and the 218 given upadacitinib 30 mg/day compared with the 212 given placebo, at 57% and 64% versus 24%.
ACR50 and 70 response rates, the proportion of patients achieving resolution of enthesitis and dactylitis, and PASI75, 90, and 100 response rates were also significantly higher in the upadacitinib groups versus the placebo arm. Adalimumab was not included as a study drug in SELECT-PsA-2.
“Efficacy [of upadacitinib] was demonstrated in all measures of the various clinical domains of psoriatic arthritis,” summarized Mease, noting that “efficacy was observed as early as week 2.”
Both presenters said that the safety profile of upadacitinib in the SELECT-PsA-1 and SELECT-PsA-2 trials was consistent with the known safety profile in patients with rheumatoid arthritis.
In SELECT-PsA-1, “broadly speaking, the adverse events [AEs] were balanced across the groups,” said McInnes. A total of 66.9%, 72.3%, 59.6%, and 64.8% of patients in the upadacitinib 15 mg, upadacitinib 30 mg, placebo, and adalimumab groups experienced AEs, and the corresponding rates of serious AEs were 3.3%, 6.1%, 3.1%, and 3.7%.
Similarly, the proportion of patients experiencing AEs in SELECT-PsA-2 was 64.0%, 78.0%, and 65.6% in the upadacitinib 15 mg, upadacitinib 30 mg, and placebo arms, respectively, and a corresponding 5.7%, 8.3%, and 1.9% experienced serious AEs.
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Alexis Ogdie comments on the results of the SELECT-PsA-1 and SELECT-PsA-2