Dose-ranging study of decernotinib as monotherapy in patients with active RA
Multidrug therapy is the common treatment approach for rheumatoid arthritis (RA). In this study the author has successfully cater the area of unmet need by assessing the efficacy and safety of decernotinib monotherapy in patients with RA.
To assess the efficacy and safety of oral decernotinib monotherapy in a 12-week, randomized, double-blind, placebo-controlled, dose-ranging study of patients with RA.
Two hundred four adults with active RA who had been unsuccessfully treated with ≥1 disease-modifying antirheumatic drug were administered placebo tablets or decernotinib twice a day at dosages of 25 mg, 50 mg, 100 mg, or 150 mg.
Primary measures of efficacy at week 12 were the response rate according to the American College of Rheumatology 20% improvement criteria (ACR20) and mean change from baseline in the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP).
At week 12, ACR20 response rates were 39.0%, 61.0%, 65.0%, and 65.9% in 25-mg, 50-mg, 100-mg and 150-mg groups, respectively, and were significantly higher in 50-mg group (P = 0.007) and 100-mg and 150-mg groups (P = 0.002) as compared to the response rates in the placebo group (29.3%).
The mean change from baseline in DAS28-CRP was greater in 50-mg, 100-mg, and 150-mg groups as compared to the placebo group (P < 0.001). Decernotinib treatment resulted in higher ACR50 and ACR70 response rates, more patients with DAS28-CRP scores <2.6, and improvements in the Health Assessment Questionnaire disability index as compared to placebo. The most common adverse events in any decernotinib group were nausea (6.1%), headache (4.3%), an increase in levels of alanine aminotransferase (4.3%), and hypercholesterolemia (3.7%). In the groups receiving decernotinib, there was an increased risk of infections and increased liver transaminase levels.
Decernotinib was efficacious in improving clinical signs and symptoms of RA at week 12 at dosages of 50–150 mg twice a day. Infections and increases in liver transaminase and lipid levels were noted as potential safety signals.