Reclassifying DMARDs: Targeted Versus Conventional Therapies

Rheumatologists in Austria and The Netherlands have proposed a reclassification of synthetic disease-modifying antirheumatic drugs (DMARDs) into targeted synthetic DMARDs and conventional synthetic DMARDs. The new classification also differentiates between biological original DMARDs and biosimilar DMARDs.

Disease-modifying antirheumatic drugs (DMARDs) are treatments for rheumatoid arthritis (RA) that slow the progression of joint damage and reduce the immune responses that contribute to pain and inflammation. A group of Austrian and Dutch rheumatologists recognize the broad categories of biologic and synthetic DMARDs, but propose further differentiation of synthetic DMARDs into conventional and targeted therapies and biologic DMARDs into original and biosimilar therapies.

According to Smolen and colleagues, conventional synthetic DMARDs (csDMARDs) were not developed based on a specific mechanism of action. For instance, although leflunomide specifically inhibits dihydroorotate dehydrogenase, leflunomide was not developed specifically to target this enzyme. Because the mechanism of action was discovered after the drug development stage, leflunomide is classified as a csDMARD.

Smolen and colleagues argue that the rational development and design of the newer synthetic medications differentiates the newer, targeted synthetic DMARDs (tsDMARDs) from the older csDMARDs, such as methotrexate, sulfasalazine, leflunomide, hydroxychloroquine, and gold salts. The orally bioavailable, synthetic, small-molecule Janus kinase (JAK) inhibitor tofacitinib is one example of a tsDMARD. The authors also classified several medications in development for RA treatment, and medications with pending indications for RA, such as fostamatinib, baricitinib, apremilast, imatinib, and ibrutinib as tsDMARDs.

Smolen and colleagues also propose a division of biologic DMARDs into 2 categories: biological original treatments (boDMARDs) and biosimilar treatments (bsDMARDs). Biosimilar treatments are generic drugs that meet regulatory criteria allowing generic manufacturers to emulate the design of innovator products after patent expiration.

To reiterate, the new terminology separates synthetic DMARDs into tsDMARDs and csDMARDs. The emerging availability of biosimilars warrants classification of biologic DMARDs into boDMARDs and bsDMARDs. Clarification of terminology in treatments for RA may lead to clearer communication about the nature of available treatments.