Brepocitinib superior to placebo in reducing psoriatic arthritis signs, symptoms
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Key takeaways:
- Patients with psoriatic arthritis who received 30 mg and 60 mg daily doses of brepocitinib had significantly greater ACR20 response rates vs. those who received placebo.
- Improvements in disease activity began as early as week 4 in those receiving brepocitinib.
Brepocitinib, in doses of either 30 mg or 60 mg, is superior to placebo in reducing signs and symptoms of psoriatic arthritis and is “generally well tolerated” through 52 weeks, according to data published in Arthritis & Rheumatology.
“Despite a variety of treatment options, the PsA treatment goals of decreasing disease activity, inducing remission and improving health-related quality of life (HRQoL) and function, as well as preventing structural damage and complications, remain an unmet need,” Philip Mease, MD, of Swedish Medical Center and the University of Washington, in Seattle, and colleagues wrote. “[Janus kinase inhibitors (JAKis)] are a promising class of emerging treatment options for PsA due to their mechanism of action.
“Brepocitinib is a JAKi with selectivity for [tyrosine kinase 2 (TYK2)] and JAK1 over JAK2 and JAK3,” they added. “TYK2 inhibition by brepocitinib provides greater blockade of IL-12 and IL-23 signaling compared with JAK1 inhibition alone; this reduces production of IL-17, one of the major effector cytokines in the pathogenesis of psoriatic disease.”
To investigate the safety and efficacy of brepocitinib (Priovant Therapeutics) in patients with PsA, Mease and colleagues conducted a phase 2b, randomized, double-blind, placebo-controlled, dose-ranging, parallel-treatment group study. Patients were eligible to participate in the trial if they were aged 18 to 75 years and had been diagnosed with PsA for at least 6 months. The analysis ultimately included 218 patients who were randomized to receive brepocitinib 10 mg, 30 mg, 60 mg or placebo once daily.
The primary efficacy endpoint was the proportion of patients who achieved the American College of Rheumatology 20% (ACR20) response at week 16. Secondary efficacy endpoints included the proportion of patients who achieved ACR20, ACR50, ACR70, PASI75 or PASI90 at any and all timepoints. Safety endpoints included the occurrence of treatment-emergent adverse events, serious adverse events and serious infection events. Additionally, the researchers monitored study withdrawals due to treatment-emergent adverse events, laboratory abnormalities, vital changes and changes in electrocardiogram findings.
According to the researchers, 66.7% of patients who received 30 mg, and 74.6% of those treated with 60 mg, of brepocitinib achieved ACR20 response, compared with 43.3% of those who received placebo, at 16 weeks (P = .0006). In addition, the patients receiving brepocitinib demonstrated “significantly higher” ACR50, ACR70, PASI75 and PASI90 response rates, the researchers noted. In all cases, response rates were maintained or improved through 52 weeks of surveillance.
There were 15 serious adverse events reported in 12 patients, of whom six were in the brepocitinib 30 mg and 60 mg groups. There were no deaths or major adverse cardiovascular events.
“Compared with placebo, treatment with brepocitinib 30 or 60 mg QD was significantly more effective at reducing the signs and symptoms of PsA and improving function and HRQoL at 16 weeks, including significant improvements in the primary endpoint of ACR20 response rate,” Mease and colleagues wrote. “Measurable improvements in disease activity were seen in the brepocitinib 30 and 60 mg groups as early as week 4.
“Consistent with findings from previous studies in patients with alopecia areata and plaque psoriasis, brepocitinib was generally well tolerated at all doses,” they added. “The 60 mg once daily group experienced the most [adverse events] and study discontinuations during the extension period, but the majority of AEs were mild or moderate in severity.”
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