NEW YORK – Tocilizumab monotherapy is a viable alternative treatment for patients with moderate to severe rheumatoid arthritis who have not responded to methotrexate in use with the biologic, according to Dr. Yusuf Yazici, speaking at a meeting sponsored by New York University.

"One paradigm of RA treatment is that a biologic alone is equivalent to methotrexate alone, but that the combination is better. These data suggest that tocilizumab may possibly be used alone," said Dr. Yazici, director of the Seligman Center for Advanced Therapeutics and Behçet’s Syndrome Evaluation, Treatment, and Research Center at the NYU Hospital for Joint Diseases.

Data from the ACT-RAY trial, which was presented by Dr. Maxime Dougados, professor of rheumatology at René Descartes University, Cochin Hospital, Paris, at the 2011 annual meeting of the American College of Rheumatology, showed that the DAS28 remission rate was 35% for tocilizumab plus placebo, compared with 40% for tocilizumab plus methotrexate, a difference that was not statistically significant (P = .19; 95% confidence interval, 2.4%-13.7%).

There were also no significant differences among ACR 20/50/70/90 response rates between groups. For both groups, the onset of action was comparable, with 18.1% of the combination group and 15.2% of the tocilizumab monotherapy group achieving remission by week 8.

The ACT-RAY trial is a phase IIIb double-blind 2-year study of biologic-naive adults with moderate to severe active RA who were considered to be inadequate responders to methotrexate. Of the 556 patients enrolled, 279 were randomized to tocilizumab (8 mg/kg every 4 weeks) plus a stable dose of methotrexate and 277 received the same dose of tocilizumab plus placebo for 24 weeks. Radiographs taken of the hands and feet at baseline and 24 weeks were assessed for structural changes.

Secondary outcomes, such as progression of structural damage as measured by the Genant-modified Sharp score (GSS) and joint space narrowing score, also showed no significant differences between treatment groups. On several measures, including total GSS scores, the proportion of patients with no progression of structural damage was similar (for example, 65.3% for the combination treatment vs. 58.7% for tocilizumab monotherapy). Improvements from baseline on the Health-Assessment Questionnaire Disability Index and rheumatoid arthritis quality of life score were comparable.

As far as safety, rates of adverse events, serious adverse events, and serious infections per 100 patient-years were indistinguishable.

"There are other pieces of information pointing in the same direction, where for most of the outcome measures there was no difference between the groups; however, some favored the combination arm. None of the studies by themselves prove that monotherapy is as good as combination treatment, but the data provide information that tocilizumab monotherapy is a good option for some patients," said Dr Yazici.

"It would be good to do a study that looks at truly methotrexate-naive patients with early disease and see how tocilizumab monotherapy compares to methotrexate alone and a combination of tocilizumab with methotrexate.

"While the AMBITION study (Ann. Rheum. Dis. 2010;69:88-96) reported that tocilizumab monotherapy was better than methotrexate alone, one-third of patients had been on methotrexate before the trial but discontinued treatment. Those patients are not going to have as robust a response with methotrexate as those who are truly methotrexate naive."

Dr. Yazici also spoke about the results of the ACT-STAR study, a prospective, 24-week open label trial, which were presented at the 2011 annual meeting of the American College of Rheumatology by Dr. Michael E. Weinblatt, codirector of clinical rheumatology at the Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, Boston.

In this trial, the enrolled patients were inadequate responders to anti-tumor necrosis factor (anti-TNF) therapy. No significant differences were found on the ACR 20/50/70 among those treated with tocilizumab monotherapy (8 mg/kg, n = 129) and those who received a combination of tocilizumab plus a DMARD (those in the combination group received either tocilizumab 8 mg/kg throughout the trial (n = 221) while others began with a 4 mg/kg dose which then was raised to 8 mg/kg (n = 322)).

While the study concluded that tocilizumab monotherapy was similar to combination therapy, Dr. Yazici commented that the randomization process used was inadequate as this was an open label trial and the data needs to be interpreted with this in mind. He said, "However, all these studies suggest that there may be a role for tocilizumab monotherapy in patients who have had an inadequate response to methotrexate in the past."

Tocilizumab, a biologic that targets interleukin-6 receptors, was approved in the United States in January 2010 for the treatment of adults with moderate to severe, active RA who have had an inadequate response to one or more TNF inhibitors. Tocilizumab monotherapy could be particularly beneficial for those with RA who respond poorly to methotrexate or experience adverse effects from it.

Dr. Yazici serves as a consultant to Bristol-Myers Squibb and Genentech.

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