WASHINGTON — Tofacitinib, which was recently approved by the US Food and Drug Administration for the treatment of moderate to severe rheumatoid arthritis (RA) not responsive to methotrexate, is effective in patients with a suboptimal response to previous biologic therapies. The response to the drug was maintained during 2-year extension studies.
Lead investigator G.R. Burmester, MD, from the Charité University Hospital in Berlin, Germany, reported the results here at ACR 2012.
"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 previous TNF [tumor necrosis factor] inhibitors. No new safety signals emerged during the trial," said Dr. Burmester.
At last year's annual ACR meeting, Dr. Burmester reported the results of a study in which 399 patients with an inadequate response to TNF inhibitors were treated with tofacitinib. This year, he reported pooled data from 614 patients with an inadequate response to TNF inhibitors who were enrolled in phase 2 and 3 trials and treated with tofacitinib for 24 months.
Both 5 mg and 10 mg of tofacitinib were superior to placebo on the ACR20/50/70 scale at month 3. The same pattern was observed whether patients failed on 1, 2, or 3 previous TNF inhibitors, he reported.
At month 3, patient-reported outcomes for physical function (Health Assessment Questionnaire-Disability Index (HAQ-DI), body pain (SF-36), and fatigue (FACIT) were significantly better in both tofacitinib groups than in the placebo group.
To analyze long-term efficacy in 2 large phase 3 trials and 3 long-term open-label extension studies, data were pooled for both tofacitinib doses. Not all patients completed 24 months of therapy, he explained.
However, ACR20/50/70 responses were maintained over 24 months, as were disease activity score (DAS)28 remission rates.
"Low disease activity, as measured by the DAS score, was reached in about 40% of these difficult-to-treat patients. This is remarkable from a clinical standpoint," Dr. Burmester said during his presentation.
Responses to the 3 patient-reported outcome measures (HAQ-DI, SF-36, and FACIT), favoring tofacitinib, were consistent at 24 months.
Tofacitinib has 2 advantages, according to Eric L. Matteson, MD, from the Mayo Clinic in Rochester, Minnesota. It is a Janus kinase (JAK) inhibitor with a novel biochemical mechanism, and it is administered orally. "Both of these features will be attractive to physicians and patients," Dr. Matteson noted.
"Clinical trials don't represent RA patients at large because they have many exclusions. Whether tofacitinib is adopted in clinical practice will depend on its efficacy and safety.... Initially, tofacitinib will be used in patients who have failed on a biologic therapy," he explained.
The mechanism of action of tofacitinib is different than that of the 5 currently approved TNF inhibitors, and it is an oral drug, which will make it interesting to rheumatologists, he said.
The pricing structure will also be important. "My impression is that it will be similar to the price of currently available biologics, which are expensive," Dr. Matteson noted.
"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," he concluded.
Dr. Burmester reports financial ties with Abbott, Bristol-Myers Squibb, Merck Sharpe and Dohme, Pfizer, Roche, and UCB. Dr. Matteson reports financial ties with Centecor/Johnson & Johnson, Genentech and Biogen Idec, Hoffman-La Roche, Human Genome Sciences, Pfizer, Novartis Pharmaceutical Corporation, Roche Pharmaceuticals, UCB Group, and Horizon Pharma.
ACR 2012: Abstract L12. Presented November 13, 2012.
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Cite this: Tofacitinib Effective in RA After Poor Response to Biologics - Medscape - Nov 15, 2012.