In all measures of efficacy, response rates with tocilizumab were substantially higher than with adalimumab, which inhibits tumor necrosis factor (TNF), in a 24-week, double-blind, placebo-controlled trial, said Cem Gabay, MD, PhD, of University Hospitals of Geneva in Switzerland.
Adverse effects with the two drugs were about equal, Gabay said at a press conference held before his formal presentation of study results at the European League Against Rheumatism's (EULAR) annual meeting.
But EULAR President Maxime Dougados, MD, of Rene Descartes University in Paris, suggested that the trial stacked the deck in favor of tocilizumab by choosing adalimumab as the comparator.
He told MedPage Today that earlier monotherapy studies had indicated that adalimumab was less effective than other anti-TNF drugs such as etanercept (Enbrel).
But he also emphasized that adalimumab is very widely used clinically, so in that sense it was an appropriate comparator.
Gabay said that, although biologic drugs are not approved in the U.S. or Europe as monotherapy — they are supposed to be given in combination with methotrexate or other conventional disease-modifying drugs — in practice, a significant number of patients do receive them as single agents.
He cited earlier research indicating that 30 percent of patients on biologic drugs for rheumatoid arthritis in the U.S. receive them as monotherapy, with similar percentages in Western Europe.
The off-label usage results from some patients' inability to tolerate methotrexate or simply their preference for single-agent therapy, Gabay said.
The current trial, called ADACTA, randomized 326 patients to either 8 mg/kg of tocilizumab by IV infusion very 4 weeks or 40 mg of adalimumab by subcutaneous injection every 2 weeks. Because of the different schedules and routes of administration, the double-blinding required placebo infusions in the adalimumab arm and subcutaneous placebo injections for the tocilizumab group.
Treatment lasted for 24 weeks, although lack of response at 16 weeks qualified patients for additional medications.
To qualify for the study, patients had to be biologics-naive with a Disease Activity Scale-28 (DAS28) score greater than 5.1, with at least six swollen and eight tender joints, and either an erythrocyte sedimentation rate of more than 28 mm/hr or C-reactive protein level of at least 1.0 mg/dL at baseline.
Concomitant steroids and NSAIDs at established stable doses were permitted.
On the study's primary outcome measure, change in DAS28 score from baseline, tocilizumab was clearly superior with a decline in average scores of 3.3 points, versus 1.8 with adalimumab.
Rates for all adverse events, serious adverse events, overall infections, and serious infections were virtually identical between treatments, Gabay said.
There were two deaths in the study, both in the tocilizumab arm. One involved an illicit drug overdose and was considered unrelated to treatment. In the other, no cause was identified because the family refused an autopsy, although the patient had a variety of comorbid conditions including interstitial lung disease, hypertension, and peripheral vascular disease and was a smoker. Due to the uncertainty, Gabay and colleagues classified the death as "possibly" related to tocilizumab.
Gabay said the response rates in the study were similar to those seen in earlier trials in which the drugs were used with methotrexate, as called for in their labels.
He said one could interpret the findings as suggesting that methotrexate may not actually contribute much to the efficacy of the biologic agents.
But both Gabay and Dougados stressed that such a conclusion would be premature in the absence of studies directly comparing monotherapy with biologic-methotrexate combination treatment.
For now, Dougados said, adding biologics to methotrexate should remain the standard of care.
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