By Phoebe Starr
Washington, DC—Tofacitinib (Xeljanz), an oral Janus kinase (JAK) inhibitor, is effective in the treatment of patients with rheumatoid arthritis (RA) whose disease has an inadequate response to previous treatment with biologic therapies, and the response with tofacitinib is maintained for 24 months. These were the findings of an analysis of data from randomized trials in the development program for tofacitinib and were presented at the 2012 meeting of the American College of Rheumatology (ACR).
“We observed a consistent improvement in signs and symptoms, physical function, and patient-reported outcomes with tofacitinib regardless of whether patients had an inadequate response to 1 or 2 prior TNF [tumor necrosis factor] inhibitors. No new safety signals emerged during the trial,” stated lead investigator Gerd Burmeister, MD, Professor, Charité Hospital Clinic for Rheumatology and Clinical Immunology, Berlin, Germany.
Tofacitinib was recently approved by the US Food and Drug Administration for the treatment of moderate-to-severe RA that is not responsive to methotrexate (Trexall). This new JAK inhibitor works by a different mechanism than other biologics used for the treatment of RA, and its oral formulation is perceived as an advantage.
This pooled analysis included data for 614 patients whose disease had an inadequate response to TNF inhibitors and who were enrolled in 9 randomized phase 2 and phase 3 clinical trials of tofacitinib lasting ≥3 months.
At month 3, tofacitinib 5-mg and 10-mg doses were superior to placebo for the treatment of the signs and symptoms of RA as measured by the ACR criteria for at least a 20%, 50%, or 70% improvement (ACR20/ACR50/ACR70) from baseline. Improvement was observed regardless of whether patients had failed treatment with 1, 2, or 3 previous TNF inhibitors.
Both dosages were significantly superior to placebo based on the patient-reported outcomes for physical function (ie, Health Assessment Questionnaire Disability Index [HAQ-DI]), body pain (ie, the 36-Item Short-Form Health Survey [SF-36]), and fatigue (ie, Functional Assessment of Chronic Illness Therapy [FACIT]).
In addition, the investigators looked at the long-term efficacy of tofacitinib based on 2 large phase 3 clinical trials and 3 long-term, open-label, 24-month extension studies. In this analysis, data were pooled for the 5-mg and the 10-mg doses of tofacitinib.
ACR20/ACR50/ACR70 responses to tofacitinib that were observed at month 3 were maintained over 24 months. The rates of remission, as defined by DAS28 (Disease Activity Score in 28 joints), were also maintained for 24 months.
Approximately 40% of the patients with RA that had failed on other biologic therapies had low disease activity over 24 months, Dr Burmeister said.
Patient-reported outcomes measures (ie, HAQ-DI, SF-36, and FACIT) showed that responses favoring tofacitinib remained consistent over 24 months.
Despite these encouraging results, the investigators noted that more data are needed to determine the role of this drug in clinical practice.
“Tofacitinib looks good in the initially promising trials. We need experience in routine clinical practice to define the role of this agent in moderate-to-severe RA,” stated Eric L. Matteson, MD, Chief of Rheumatology, Mayo Clinic, Rochester, MN, who was not involved in this study.