Tofacitinib, the first in a new class of oral treatments known as Janus kinase (JAK) inhibitors, was accepted for regulatory approval yesterday. JAK inhibitors interrupt signalling downstream of multiple cytokines, rather than blocking one cytokine at a time in the manner of tumour necrosis factor (TNF) inhibitors.
In the phase 3 ORAL trial programme involving more than 4000 patients with moderate to severe active RA, tofacitinib consistently reduced signs and symptoms of RA. Adverse events, including infections and reduced neutrophil counts, were generally mild to moderate.
"This looks like an impressive drug. This is some of the most important phase 3 data we’ve seen," said Paul Emery, Professor of Rheumatology and Head of the Academic Unit of Musculoskeletal Medicine at the University of Leeds.
In one 12-month study ('ORAL Standard'), investigators randomised 717 patients to receive tofacitinib (5mg or 10mg twice daily), adalimumab (40mg subcutaneously every two weeks) or placebo, in addition to methotrexate. Although the study was not designed as a head-to-head superiority or non-inferiority comparison, the data for tofacitinib and adalimumab were numerically similar for all outcomes.
After 6 months, ACR20 response rates were 51.5% and 52.6% for tofacitinib 5mg and 10mg, respectively, compared with 47.2% for adalimumab and 28.3% for placebo. Serious adverse events were more common with tofacitinib than adalimumab, although most adverse events were mild.
Tofacitinib, previously known as tasocitinib, has been developed by Pfizer. It is also being tested in psoriasis, inflammatory bowel disease and renal transplantation.