CHICAGO—The investigational oral immunomodulator tofacitinib shows promise, when combined with methotrexate, in treating active rheumatoid arthritis (RA) that does not respond well to tumor necrosis factor (TNF) inhibitors, a phase III study finds.
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Explore This IssueApril 2012
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Six-month results of this multicenter trial, named the Oral Step Study, were reported here at the 2011 ACR/ARHP Annual Scientific Meeting in November. The abstract (number 718) was among the clinical studies presented during the “Discovery 2011” plenary session, which included research on scleroderma. [Editor’s note: This session was recorded and is available via ACR SessionSelect at www.rheumatology.org.]
In the Oral Step Study, four groups of patients, with a mean RA duration of 11 years, received methotrexate at a dose of 7.5 to 25 mg weekly. Two of the groups also received tofacitinib twice daily, either 5 mg (n=133) or 10 mg (n=134). The other two groups (with 66 patients each) received placebo for three months and then crossed over in a blinded, prerandomized order to either 5 or 10 mg of tofacitinib for the final three months.
Compared with placebo, tofacitinib demonstrated significantly better improvement in signs and symptoms of RA, physical function, and disease activity at both doses, said study investigator Gerd R. Burmester, MD.
All groups showed improved mobility, pain, and function, but diet and exercise was superior in virtually all measures.
—Stephen P. Messier, PhD
“It’s quite remarkable that even if the patients had failed two or more TNF-inhibiting agents, they still had a significantly increased response to tofacitinib,” said Dr. Burmester, professor of medicine and director of rheumatology and clinical immunology at Charité-University Medicine Berlin. “This was a really sick patient population.”
About 35% of patients had used two or more TNF inhibitors without success, and 65% had inadequate response to one prior TNF inhibitor. Effects of tofacitinib were as rapid as typically seen with TNF inhibitors, said Dr. Burmester, who reports receiving research funding and consulting and speaking fees from the study sponsor, Pfizer.
One death due to pulmonary embolism occurred in the 10-mg tofacitinib group. Dr. Burmester said the cause possibly was concomitant postmenopausal hormone therapy.
The meeting’s basic science chair, Richard F. Loeser, Jr., MD, told The Rheumatologist that this study could change clinical practice.
“If we find out that tofacitinib is as effective as injections of TNF inhibitors, that will be a big breakthrough,” said Dr. Loeser, section head of molecular medicine at Wake Forest School of Medicine in Winston-Salem, N.C.
In another RA study, Androniki Bili, MD, a rheumatologist at Geisinger Medical Center in Danville, Pa., reviewed electronic health records of an inception cohort of 1,829 patients with RA (abstract 719). She and her coworkers studied whether methotrexate and TNF-α inhibitors independently reduced the risk of cardiovascular disease (CVD)—a major cause of death in patients with RA—over a median follow-up of about three years. They classified patients as “ever users” or “never users” of methotrexate (n = 1,119 and 710, respectively) and TNF-α inhibitors (588 users versus 1,241 nonusers).