Tofacitinib Recommended for FDA Approval to Treat Rheumatoid Arthritis
The Arthritis Advisory Committee to the U.S. FDA has voted 8-2 to recommend approval of tofacitinib for the treatment of adult patients with moderately to severely active rheumatoid arthritis. If approved, tofacitinib would be the first new oral disease-modifying anti-rheumatic drug (DMARD) for rheumatoid arthritis in more than 10 years and the first oral biologic drug belonging to a new class of drugs known as JAK (Janus kinase) inhibitors.
The FDA is expected to make their decision on Pfizer’s new drug for rheumatoid arthritis in August 2012.
Unlike other currently existing biologic drugs that target extracellular entities, such as proinflammatory cytokines, tofacitinib targets intracellular pathways that operate as hubs in the inflammatory cytokine network, according to Pfizer. Tofacitinib has been studied in about 4,800 patients.
There have been five Phase III trials and two ongoing, long-term extension studies in numerous countries around the world. The drug was recommended for approval despite some concern over side effects including lymphoma, infection, and elevated cholesterol levels. Proponents believe there is a need for more treatment options, especially for rheumatoid arthritis patients who have not responded to other treatments or for those who develop antibodies to current biologic treatments and have to discontinue use.
Tofacitinib (formerly tasocitinib, CP-690550) is a drug being investigated by Pfizer for the treatment of rheumatoid arthritis (RA), psoriasis, inflammatory bowel disease, and other immunological diseases, as well as for the prevention of organ transplant rejection. It is an inhibitor of the enzyme Janus kinase 3 (JAK3), which means that it interferes with the JAK-STAT signaling pathway, which transmits extracellular information into the cell nucleus, influencing DNA transcription.
Recently it has been shown in a murine model of established arthritis, tofacitinib rapidly improved disease by inhibiting the production of inflammatory mediators and suppressing STAT1-dependent genes in joint tissue. This efficacy in this disease model correlated with the inhibition of both JAK1 and 3 signaling pathways, suggesting that tofacitinib may exert therapeutic benefit via pathways that are not exclusive to inhibition of JAK3.[
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Carol Eustice