Loading

Commentary Open Access

Rethinking leflunomide in rheumatoid arthritis: Can innovative drug delivery approaches open new horizons?

  • 1Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A), Palaj, Opposite Airforce Station, Gandhinagar-382355, Gujarat, India
+ Affiliations - Affiliations

Corresponding Author

Kalpna Garkhal, Kalpna.garkhal@niperahm.res.in

Received Date: September 15, 2025

Accepted Date: November 10, 2025

Abstract

Leflunomide (LEF) is one of the most effective synthetic disease-modifying antirheumatic drugs (DMARD) which is widely prescribed for rheumatoid arthritis. But the safety issues of LEF makes its use compromised due to various side effects like hepatotoxicity, GIT disturbances, etc, and variable patient responses. The longer retention period of LEF in body is another issue which requires the washout period of almost 2 weeks using cholestyramine or activated charcoal for complete removal from the body, hence, contraindicated in pregnant women. However, the arrival of biologics and targeted synthetic DMARDs have diminished the use of LEF, although, this molecule has excellent anti-arthritic potential with maximum efficacy. Recent progress in innovative and novel drug delivery strategies for RA have yielded promising outcomes, opening new horizons for safer delivery of LEF to RA patients. Approaches like polymeric, transdermal, and lipid-based nano-cargoes have shown potential in increasing efficacy, solubility and minimizing the systemic toxicity. Furthermore, combination of LEF with other DMARDs and stimuli-triggered drug release techniques could lead to the development of integrated modalities for LEF delivery in RA patients. Here, in this commentary, we believe that if safety and efficacy issues with LEF is successfully addressed to a significant extent using smart and innovative drug delivery approaches, the underutilization can be reduced and can open new avenues for safer LEF delivery in RA patients. 

Keywords

Rheumatoid arthritis, Leflunomide, Novel drug delivery systems, Arthritis, Disease-modifying antirheumatic drugs (DMARDs)

Author Information X