JAK Inhibitor Shows Superiority in Active Rheumatoid Arthritis
Investigational drug used alone or in combination demonstrated superiority to methotrexate in patients with active rheumatoid arthritis.
Results from a phase 3 global study of an investigational drug for the treatment of patients with active rheumatoid arthritis (RA) showed superiority when used alone or in combination with methotrexate, (MTX) compared with MTX alone.
Researchers used the oral Janus kinase (JAK1/JAK2) inhibitor called baricitinib to test the efficacy in patients with RA who had zero or minimal prior conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs), and who are naïve to biologic DMARDs. Findings from the RA-BEGIN clinical trial were published in Arthritis & Rheumatology.
For the study, 558 patients were randomized 4:3:4 to receive either MTX alone, 4-mg baricitinib once daily, or 4-mg baricitinib plus MTX, for 52 weeks. The drug achieved the primary endpoint, which was defined as non-inferiority of baricitinib monotherapy to MTX based on American College of Rheumatology 20% (ACR20) response at week 24.
The results of the study revealed that baricitinib monotherapy was found to be superior to MTX at week 24, with a higher ACR20 response rate of 77% compared with 62% P ≤ 0.01. Additionally, similar findings were seen with the combination therapy.
As early as week 1, significant improvements in disease activity and physical function were observed for both of the baricitinib groups. Furthermore, compared with MTX, radiographic progression was reduced in the baricitinib arms.
The difference was statistically significant for baricitinib plus MTX. Serious adverse events (AEs) were similar across the treatment groups.
However, the rates of certain treatment-emergent adverse events, including infections, increased with baricitinib plus MTX. Malignancies, including non-melanoma skin cancer, were found in 1 patient in the MTX arm, 1 patient in the baricitinib monotherapy, and 4 patients in the baricitinib plus MTX groups.
Three deaths occurred during the trial, all of which occurred in patients in the MTX arm. The findings showed that baricitinib alone, or in combination with MTX, demonstrated superior efficacy and acceptable safety as initial therapy for patients with active RA, compared to MTX alone, according to the study.