medwireNews: The oral small-molecule tyrosine kinase 2/Janus kinase (JAK)1 inhibitor brepocitinib improves several measures of disease activity, relative to placebo, without excessive toxicity in people with psoriatic arthritis (PsA), phase 2b study findings indicate.
The data, presented at the ACR Convergence 2021 virtual meeting, revealed that almost three-quarters of participants given the highest brepocitinib dose (60 mg/day) achieved the primary outcome of an ACR20 response at 16 weeks.
The study included 218 people who had active PsA despite treatment or were intolerant to nonsteroidal anti-inflammatory drugs or DMARDs. They were randomly assigned to receive once daily brepocitinib at doses of 60 mg (n=60), 30 mg (n=60), or 10 mg (n=31), or matching placebo (n=67) for 16 weeks.
This was followed by a 36-week period during which individuals originally assigned to placebo or brepocitinib 10 mg/day were given brepocitinib 30 mg/day or 60 mg/day. Individuals already receiving these doses continued with treatment until week 52.
Philip Mease (University of Washington, Seattle, USA) reported that, at week 16, the ACR20 response rate was significantly higher among people in the brepocitinib 30 mg and 60 mg groups than in the placebo group, at 66.7% and 74.6%, respectively, versus 43.3%. The response rate in the brepocitinib 10 mg group was 64.5%.
He added that the difference in response could be seen as early as week 4 and remained high until week 52 in both the 30 mg (67.6%) and 60 mg groups (60.9%).
Furthermore, the researchers observed that ACR50 and ACR70 response rates tended to increase between weeks 16 and 52, particularly with the 30 mg dose. Specifically, the proportion with an ACR50 response increased from 48.3% at week 16 to 54.6% at week 52, while that for an ACR70 response increased from 26.7% to 41.7%.
And there was a similar pattern of improvements for other secondary outcomes such as minimal disease activity, PASI75/90 response rates, enthesitis resolution, arthritis pain, and quality of life outcomes such as fatigue and functioning.
Mease said that “brepocitinib was well-tolerated over 52 weeks of treatment, and no unanticipated safety risks emerged for this [tyrosine kinase 2/JAK1] inhibitor.”
Serious adverse events (AEs) occurred in 9.3% of patients who received brepocitinib 30 mg and 1.8% of those who received the 60 mg dose.
Half of individuals given brepocitinib 30 mg and 40.0% of those given 60 mg experienced infections, with serious infection occurring in 4.6% and 0.9%, respectively, and herpes zoster infection was reported in a corresponding 1.9% and 1.8%. By comparison, the overall infection rate in the placebo group was 23.9%.
There were no major adverse cardiovascular events, venous thromboembolic events, or deaths.
Mease concluded that “teatment with brepocitinib significantly improved signs and symptoms of psoriatic arthritis.”
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