Tofacitinib monotherapy reported to benefit rheumatoid arthritis patients
A number of medications are currently available or undergoing clinical trials for the treatment of rheumatoid arthritis and research is ongoing regarding the benefits of these drugs alone or in combination. A new study has evaluated the efficacy of tofacitinib (Xeljanz; Pfizer) alone (monotherapy) for the treatment of rheumatoid arthritis. An international team of researchers published their findings on August 9, 2012 in the New England Journal of Medicine.
The researchers conducted a phase 3, double-blind, placebo-controlled, parallel-group, six month trial. The study comprised 611 patients with rheumatoid arthritis. They were randomly assigned, in a 4:4:1:1 ratio, to 5 mg of tofacitinib twice daily, 10 mg of tofacitinib twice daily, placebo for 3 months followed by 5 mg of tofacitinib twice daily, or placebo for 3 months followed by 10 mg of tofacitinib twice daily. The primary outcome measures, assessed at month 3, were the percentage of patients with at least a 20% improvement in the American College of Rheumatology scale (ACR 20), the change from baseline in Health Assessment Questionnaire–Disability Index (HAQ-DI) scores (which range from 0 to 3, with higher scores indicating greater disability), and the percentage of patients with a Disease Activity Score for 28-joint counts based on the erythrocyte sedimentation rate (DAS28-4[ESR]) of less than 2.6 (with scores ranging from 0 to 9.4 and higher scores indicating more disease activity).
The investigators found that at month 3, a higher percentage of patients in the tofacitinib groups than in the placebo groups met the criteria for an ACR 20 response (59.8% in the 5 mg tofacitinib group and 65.7% in the 10 mg tofacitinib group vs. 26.7% in the combined placebo groups). The reductions from baseline in HAQ-DI scores were greater in the 5 mg and 10 mg tofacitinib groups than in the placebo groups (−0.50 and −0.57 points, respectively, vs. −0.19 points). The percentage of patients with a DAS28-4(ESR) of less than 2.6 was not significantly higher with tofacitinib than with the placebo (5.6% and 8.7% in the 5 mg and 10mg tofacitinib groups, respectively, and 4.4% with the placebo). Serious infections developed in six patients who were receiving tofacitinib. Common adverse events were headache and upper respiratory tract infection. Tofacitinib treatment was associated with elevations in low-density lipoprotein cholesterol (LDL; “bad cholesterol”) levels and reductions in neutrophil (white blood cell) counts.
The authors concluded that in patients with active rheumatoid arthritis, tofacitinib monotherapy was associated with reductions in signs and symptoms of rheumatoid arthritis and improvement in physical function.
In addition to its evaluation for rheumatoid arthritis, tofacitinib is being investigated for the treatment of psoriasis, inflammatory bowel disease and other autoimmune diseases; it also is being evaluated 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.
It should be noted that the trial was funded by the pharmaceutical manufacture Pfizer. The researchers are affiliated with: the Metroplex Clinical Research Center and Baylor Research Institute, both in Dallas, Texas; the Center for Rheumatology, Albany Medical College, Albany, NY ; the Division of Rheumatology, Medizinische Klinik und Poliklinik IV, University of Munich, Munich, Germany; and Pfizer, Groton, CT.
Reference: The New England Journal of Medicine