CHICAGO – Tocilizumab alone may be sufficient to meet the clinical, structural, safety, and quality of life end points of combination tocilizumab/methotrexate therapy, based on the results of additional early analyses of a 2-year, phase IIIb study of more than 500 patients with moderate to severe rheumatoid arthritis.
"The primary end point, as presented at EULAR [the European League Against Rheumatism annual congress], was not statistically significant," Dr. Maxime Dougados said at the annual meeting of the American College of Rheumatology. The remission rate according to the DAS28 (Disease Activity Score based on a 28-joint count) was 40% for those on combination therapy and 37% for those on monotherapy. "For all of the secondary end points of the study, it was exactly the same thing," he said.
Dr. Maxime Dougados
There were also no differences between the two groups in scores on ACR 20 (an evaluation reflecting a 20% improvement according to ACR criteria), ACR 50 (a 50% improvement), ACR 70, or ACR 90 assessments.
Dr. Dougados of Université René Descartes, Paris, presented new data on quality of life measures in the trial of tocilizumab, a humanized monoclonal antibody that blocks the interleukin-6 receptor.
There were no clinical or statistical differences between the two groups based on the HAQ-DI (Health Assessment Questionnaire–Disability Index) or the RAQoL (Rheumatoid Arthritis Quality of Life) questionnaire.
The results come from the ACT-RAY trial, which is a double-blind, phase IIIb study of the efficacy and safety of tocilizumab that is given with methotrexate, compared with tocilizumab in patients who did not have an adequate response to methotrexate and thus were switched from methotrexate to tocilizumab alone.
Patients had to be naive to biologics and have moderate to severe active RA (based on the 1987 ACR criteria) to be included in the ongoing 2-year trial. The disease had to be active (resulting in a DAS28 score greater than 4.4), severe (involving at least one radiologic erosion), and refractory (requiring the patient to take methotrexate).
The researchers enrolled 556 patients who did not have adequate responses to methotrexate; in all, 277 of the 279 patients in the combination therapy group and 276 of the 277 in the monotherapy group were included in the intention-to-treat and safety analyses. A total of 260 patients in the combination group and 252 in the monotherapy group completed 24 weeks of treatment.
Tocilizumab was given at 8 mg/kg every 4 weeks, and patients who had been randomized to the monotherapy group were also given a placebo.
The study’s primary end point was the percentage of patients with DAS28-based remission at week 24. The results presented at the EULAR congress showed that tocilizumab monotherapy was similar in efficacy to the combination therapy.
In terms of the structural evaluation, the researchers looked at mean changes from baseline of the Genant-modified Sharp Score (GmSS) over the first 24 weeks of the trial. The overall changes in total scores, joint space–narrowing scores, or erosion scores were considerably less than expected. The researchers expected an increase in mean GmSS of 3.5-4.0, but none of the measures was greater than 1.0 for either group. "This suggests or confirms that tocilizumab is able to prevent structural deterioration," said Dr. Dougados. However, "we have not discovered any new information" in terms of safety, he added.
Data are pending on both the sustainability of the symptomatic effect at 1 year and the progression of structural damage at 1 and 2 years.
Dr. Dougados reported that he receives consulting fees and research grants from F. Hoffmann-La Roche, which sponsored the study. Several coauthors reported significant financial relationships with pharmaceutical companies, including Hoffmann-La Roche.
*Correction, 12/20/2011: An earlier version of this story had a headline that misstated the study findings.