BERLIN – The notion of a tocilizumab-based treatment strategy without the use of methotrexate in rheumatoid arthritis patients having an inadequate response to methotrexate monotherapy has lost some of its allure in light of 52-week data from the phase IIIb ACT-RAY trial.
Preliminary results of the randomized, double-blind study reported at last fall’s annual meeting of the American College of Rheumatology showed similar clinical improvement in patients with a prior inadequate response to methotrexate alone regardless of whether they received 24 weeks of methotrexate plus tocilizumab (Actemra) or tocilizumab plus placebo. But by the 52-week mark, things had changed, Dr. Maxime Dougados reported at the annual European Congress of Rheumatology.
Dr. Maxime Dougados
At 52 weeks in the 556-patient trial, the DAS28 remission rate, defined as a DAS28 score below 2.6, had been achieved by 45.5% of patients assigned to methotrexate plus tocilizumab at 8 mg/kg given intravenously every 4 weeks, a significantly better outcome than the 36.6% rate in patients on the interleukin-6 inhibitor plus an oral placebo in lieu of methotrexate.
Moreover, while 92.4% of patients assigned to tocilizumab/methotrexate combination therapy were free of radiographic disease progression at 1 year, that was true for only 85.5% of those on tocilizumab plus placebo (P = .007).
This doesn’t mean the end for a tocilizumab-based, methotrexate-free treatment strategy in RA. But it does suggest such a strategy will likely find a niche that’s restricted to patients with contraindications or intolerance to methotrexate, rather than a broader role in patients who are able to take methotrexate but don’t show adequate benefit without an add-on biologic, according to Dr. Dougados, professor of rheumatology at Cochin Hospital and René Descartes University, Paris.
The ACT-RAY trial introduced a more convoluted treatment protocol beginning at week 24. If at that point a patient had a DAS28 score in excess of 3.2, an open-label conventional disease-modifying antirheumatic drug other than methotrexate was added – for example, azathioprine, sulfasalazine, or hydroxychloroquine. This occurred in 29% of patients on the tocilizumab/methotrexate combination and in a similar 33% of those on tocilizumab/placebo.
Of note, the 52-week ACR 20, 50, 70, and 90 rates in the two study arms were similar. Nor were there significant differences between the two groups in terms of immunogenicity as reflected in rates of antidrug antibodies or neutralizing antidrug antibodies. And the incidence of elevated liver enzymes greater than three times the upper limit of normal was significantly lower in the methotrexate-free study arm.
"Despite some signals in favor of the add-on strategy – the percentage of patients in remission at week 52 and the structural data – this analysis suggests that tocilizumab monotherapy might be an acceptable therapeutic strategy in patients with a contraindication for or intolerance to methotrexate," he concluded.
Dr. Dougados reported serving as a consultant to Roche, which funds the ACT-RAY study.