Published online Sep 18, 2014. doi: 10.5312/wjo.v5.i4.504
Revised: March 26, 2014
Accepted: May 31, 2014
Published online: September 18, 2014
Tofacitinib is the first in a new class of nonbiologic disease-modifying antirheumatic drugs (DMARDs), a targeted, synthetic DMARD, approved for the treatment of rheumatoid arthritis (RA) as monotherapy or in combination with methotrexate or other non-biologic DMARD. Tofacitinib, an orally administered Janus kinase (JAK) inhibitor, decreases T-cell activation, pro-inflammatory cytokine production, and cytokine signaling by inhibiting binding of type I cytokine receptors family and γ-chain cytokines to paired JAK1/JAK3 receptors. The net effect of tofacitinb’s mechanism of action is decreased synovial inflammation and structural joint damage in RA patients. To date, six phase 3 trials have been conducted to evaluate the safety and efficacy of tofacitinib under the oral rheumatoid arthritis triaLs (ORAL) series. This review describes the pharmacology of the novel agent, tofacitinib, and details the safety and efficacy data of the ORAL trials.
Core tip: Tofacitinib, a Janus kinase inhibitor, is a targeted, synthetic, disease-modifying antirheumatic drug (DMARD) approved for the treatment of moderately to severely active rheumatoid arthritis in patients who have had an inadequate response to methotrexate. In numerous phase 2 and 3 trials, tofacitinib has proven to be safe and effective as monotherapy or in combination with methotrexate or other non-biologic DMARDs.