The effect of baricitinib in uncoupling the disease activity and structural damage progression in RA

Janus kinase inhibitor, baricitinib, is found to be beneficial in enhancing disease-modifying effects in patients with rheumatoid arthritis, according to the findings published in Annals of the Rheumatic Diseases. This effect is conferred by detaching the connection between structural progression and disease activity in patients with rheumatoid arthritis (RA).

The study included two phases III randomized, double-blinded trials.  In a 52-week RA-BEAM trial study, RA patients with the insufficient response towards methotrexate (MTX-IR) were administered with placebo (PBO), baricitinib 4 mg, or adalimumab 40 mg on the background of methotrexate (MTX). In the RA-BEGIN study, patients who were conventional synthetic disease-modifying antirheumatic drug (csDMARD)-naïve were administered with MTX and baricitinib 4 mg or baricitinib 4 mg along with MTX.

A decrease in structural damage progression was noted in MTX-IR patients, irrespective of the disease activity states in baricitinib-treated patients (P=0.6). However, direct dependence on the disease activity states was observed in patients who received PBO, due to significant reduction in structural damage progression in patients who accomplished remission/low disease activity (REM/LDA) as opposed to patients with moderate/high disease activity (MDA/ HDA) (P=0.02). A lesser structural damage progression was noted in MDA/ HDA group of patients on baricitinib compared to PBO MDA/HDA group (P <0.001). The structural damage progression was decreased in REM/LDA compared to MDA/HDA within the MTX group (P <0.001) for csDMARD-naïve patients; whereas, comparable structural damage progression was observed, irrespective of disease activity in case of patients who received baricitinib along with MTX (P=0.5) or baricitinib monotherapy (P=0.07). Reduced structural damage progression was noted in MDA/HDA groups who received baricitinib along with MTX (p<0.001) and numerically lower with baricitinib monotherapy (p=0.07) compared to MTX.

Pedro Lopez-Romero and co-researchers concluded reduction in structural damage progression by baricitinib compared to PBO with background MTX and/ or MTX. The reduction was observed in MDA/HAD, indicating that baricitinib can induce a disease-modifying effect in all disease activity states. The present study provides a positive effect on future clinical practice or developments in the treatment of those patients, who lacked sufficient clinical improvement.

Reference: Lopez-Romero P, de la Torre I, Haladyj E, Aletaha D, Smolen JS. Baricitinib further enhances disease-modifying effects by uncoupling the link between disease activity and joint structural progression in patients with rheumatoid arthritis. Ann Rheum Dis. 2022 Feb 22:annrheumdis-2021-221323.