Baricitinib: JAK inhibition for rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA), a chronic autoimmune inflammatory disease characterized by inflammation and joint destruction, is associated with pain, progressive disability, systemic comorbidities and early death. Conventional disease-modifying antirheumatic drugs (DMARDs) and biological DMARDs (bDMARDs) have been able to achieve remission or a very low disease activity status for RA. Nevertheless, since many patients do not reach a sufficient response with DMARDs or present with unacceptable side effects, new therapies are needed. Baricitinib (LY-3009104, INCB-028050), a new potent and selective tyrosine-protein kinase JAK1/JAK2 inhibitor, has shown clinical efficacy in patients with RA refractory to aggressive standard-of-care treatment (with both conventional DMARDs and bDMARDs) when administered orally at 4 mg q.d. in pivotal phase III clinical trials. In these studies, radiographic joint damage assessments showed significant improvements with baricitinib, and the drug was well tolerated with no unexpected safety findings. A phase III study aimed at assessing long-term (4 years) safety and efficacy of baricitinib is ongoing. Registration processes are ongoing in Europe, the U.S. and Japan.

Keywords: Baricitinib; JAK1/2 inhibitors; LY-3009104; Rheumatoid arthritis; Signal transduction modulators.