Lilly's Oral JAK Inhibitor Olumiant (Baricitinib) Demonstrates Superior Improvement in Pain, Physical Function, and Morning Joint Stiffness Versus Humira in Rheumatoid Arthritis

RA-Rheumatoid Arthritis (Image source: rheumatologyadvisor.com)

June 07, 2021 / Bioon -- Eli Lilly and partner Incyte recently presented new post-hoc analysis data from a Phase 3 clinical trial of the oral JAK inhibitor Olumiant® (baricitinib) for moderate-to-severe rheumatoid arthritis (RA) at the 2021 European Congress of Rheumatology (EULAR 2021). The results showed that at 12 weeks of treatment, compared with Humira® (adalimumab) and placebo, across all levels of disease activity in patients,Olumiant 4 mg tablets demonstrated greater improvement in patient-reported outcomes: reduced duration of pain and morning joint stiffness (morning stiffness), and improved overall physical function.

Olumiant is an oral JAK inhibitor discovered by Incyte and licensed toEli Lilly。In China, Olumiant® (baricitinib) 2 mg tablets were approved in July 2019 for the treatment of moderate-to-severe active rheumatoid arthritis (RA) in adults.

Olumiant is a Janus kinase (JAK) 1/2 inhibitor administered orally once daily, indicated for adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs), and may be used in combination with methotrexate or other non-biologic DMARDs.

In this post-hoc analysis, 1,305 patients from the Phase 3 RA-BEAM study were randomized into three treatment arms: Olumiant (oral, once daily, 4 mg), Humira (injection, every other week, 40 mg), and placebo, all receiving concurrent background methotrexate therapy. Pain was assessed using a 0–100 mm visual analog scale (VAS), with higher scores indicating greater pain severity. Physical function was evaluated using the HAQ-DI scale, where lower scores denote better physical function and less disability. Patient-reported duration of morning joint stiffness (in minutes) and fatigue were assessed using the FACIT-F scale, with higher scores indicating less severe fatigue. Disease activity was measured using the CDAI and categorized as remission (REM, ≤2.8), low disease activity (LDA, >2.8 to ≤10), moderate disease activity (MDA, >10 to ≤22), or high disease activity (HDA, >22).

A linear regression model was fitted to assess the relationship between the change in patient-reported outcomes (response) at Week 12 and the CDAI score at Week 12 (primary explanatory variable), to evaluate the degree of improvement in patient-reported outcomes across the spectrum of disease activity levels in patients receiving 4 mg Olumiant compared with placebo and Humira. Missing values were imputed using the Last Observation Carried Forward (LOCF) method.

The analysis results showed that: during the 12-week treatment period, compared with Humira and placebo, patients treated with Olumiant 4 mg demonstrated greater improvements in pain relief and physical function, as well as a reduction in the duration of morning joint stiffness. These differences in pain relief were independent of disease activity during treatment. In this analysis, after 12 weeks of treatment, patients receiving Olumiant 4 mg showed greater improvement in fatigue compared with placebo, which was similar to that of Humira. Safety results were consistent with the established classRheumatic arthritisThe safety analysis results for patients receiving oral Olumiant were consistent. Detailed efficacy data are presented in the table below.

Peter C. Taylor, first author of this post-hoc analysis and Professor of Musculoskeletal Medicine at the University of Oxford, stated: “Despite the availability of treatment options, patients with rheumatoid arthritis continue to live with daily symptoms, including pain, which continue to limit their daily activities. This analysis provides valuable insights for rheumatologists to help reduce disease activity and address the daily symptoms that are important to patients.”

Post hoc analysis data (Click image to view larger version)

The active pharmaceutical ingredient of Olumiant is baricitinib, a selective, reversible JAK1 and JAK2 inhibitor currently under clinical development for various inflammatory diseases andAutoimmunitytreatment of diseases, including rheumatoid arthritis (RA), psoriasis,DiabetesKidney disease, atopic dermatitis (AD), systemicLupus Erythematosus(SLE), etc. There are four JAK enzymes: JAK1, JAK2, JAK3, and TYK2. JAK-dependent cytokines are involved in various inflammatory andAutoimmunity…the pathogenesis of the disease, suggesting that JAK inhibitors could potentially be widely utilized in the treatment of various inflammatory diseases. In kinase assays, baricitinib demonstrated a 100-fold greater inhibitory potency against JAK1 and JAK2 compared to JAK3.

Olumiant is an oral JAK inhibitor discovered by Incyte and licensed toEli LillyTo date, Olumiant has been approved and marketed in more than 75 countries (including the United States, China, the European Union, and Japan) for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA). Additionally, Olumiant has been approved in more than 40 countries (including the entire European Union and Japan) for the treatment of adult patients with moderate-to-severe atopic dermatitis (AD). Recently, Olumiant has also been approved in Japan for the treatment of COVID-19-associated pneumonia in hospitalized adult patients.

For the treatment of RA, the approved doses of Olumiant are 4 mg and 2 mg in the European Union, and 2 mg in both the United States and China. Regarding administration, Olumiant is administered orally once daily and may be used as monotherapy or in combination with methotrexate (MTX) or other non-biologic disease-modifying antirheumatic drugs (non-biologic DMARDs). Concomitant use of Olumiant with other JAK inhibitors, biologic DMARDs, or potent immunosuppressants (such as azathioprine and cyclosporine) is not recommended. Notably, the US prescribing label for Olumiant includes a boxed warning regarding serious infections and malignancies...Tumorand the risk of thrombosis. (Bioon.com)

Original Source: OLUMIANT® Improved Pain, Physical Function and Morning Joint Stiffness in Rheumatoid Arthritis in Phase 3 Post-Hoc Analyses