JAK inhibition for the treatment of rheumatoid arthritis: a new era in oral DMARD therapy

Introduction: In rheumatoid arthritis (RA) there is a significant medical need for safe and effective oral disease-modifying anti-rheumatic drugs (DMARDs) for patients who respond inadequately to methotrexate, the first-line therapy in RA. Oral agents targeting Janus-associated kinases (JAKs) are the most promising new agents in clinical development. This review describes the preclinical and clinical activities of the most advanced JAK inhibitors with different JAK selectivity profiles. Areas covered: This review first describes the current treatment landscape and the pathophysiology of RA. Role for cytokines in the disease pathogenesis followed by significance of JAK/STAT pathway in cytokine signaling are discussed. Available chemical description and enzymatic data on the most advanced JAK inhibitors in clinical development are provided. Preclinical and clinical results that are publicly available are summarized. Review of literature was conducted using National Library of Medicine (NLM) database, ‘PubMe...