By Lynda Williams, Senior MedWire Reporter
The novel oral Janus kinase (JAK) inhibitor tofacitinib significantly reduces signs and symptoms of rheumatoid arthritis (RA), report two phase III trials published in TheNew England Journal of Medicine.
The first study, conducted in 717 RA patients using a stable dose of methotrexate, showed that patients who were randomly assigned to receive tofacitinib 5 mg or 10 mg twice daily were significantly more likely to achieve a 20% reduction in the American College of Rheumatology (ACR 20) score after 6 months than placebo-treated patients (51.5 and 52.6 versus 28.3%, respectively).
Although the study was not powered for a formal inferiority comparison, tofacitinib also showed comparable efficacy to treatment with the anti-tumor necrosis factor (TNF) agent adalimumab (40 mg every 2 weeks), which gave a 47.2% reduction in ACR 20 scores, report Bethanie Wilkinson (Pfizer Inc., Groton, Connecticut, USA) and co-authors.
In an accompanying editorial, David Fox (University of Michigan, Ann Arbor, USA) notes, however, that extended research is required to determine the impact of tofacitinib on radiographic endpoints, commenting: "The combination of methotrexate and a TNF inhibitor arrests the progression of radiographic damage in most patients with rheumatoid arthritis, and it will be important to determine whether the combination of methotrexate and tofacitinib is similarly effective."
Tofacitinib at both 5 mg and 10 mg doses was associated with significantly more serious adverse events than adalimumab between months 6‑12 (4.9 and 3.0% vs 3.4%, respectively), and more serious infections throughout the study (3.4 and 4.0 vs 1.5%). Two patients given 10 mg doses developed pulmonary tuberculosis.
In addition, tofacitinib-treated patients experienced elevated high- and low-density lipoprotein cholesterol compared with adalimumab- and placebo-treated individuals, but a comparable mild decrease in neutrophils.
Acknowledging the nine biologic agents against five targets that are currently licensed in the USA for RA, Fox says: "A better understanding of the safety profile of tofacitinib will influence the consideration of when in the course of rheumatoid arthritis clinicians should consider this novel approach."
A second study published in the NEJM, by Roy Fleischmann (Metroplex Clinical Research Center, Dallas, Texas, USA) and co-authors, showed that for RA patients who failed to respond to at least one nonbiologic or biologic disease-modifying drug, tofacitinib therapy met two of the three specified efficacy outcomes.
The trial randomly assigned 611 patients to receive tofacitinib 5 mg or 10 mg twice daily, or placebo for 3 months followed by tofacitinib 5 mg or 10 mg for 3 months. An ACR 20 response was achieved at 3 months by 59.8% of patients given the 5 mg dose and 65.7% of 10 mg treated patients versus 26.7% of placebo-treated patients.
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