Kate Johnson

June 07, 2012

June 7, 2012 (Berlin, Germany) — Monotherapy with the interleukin-6 (IL-6) receptor inhibitor tocilizumab (Actemra, Hoffmann-La Roche Inc) showed efficacy superior to that of monotherapy with the tumor necrosis factor (TNF) inhibitor adalimumab (Humira, Abbott) in reducing signs and symptoms of rheumatoid arthritis (RA), according to 24-week data from the phase 4 ADACTA (ADalimumab ACTemrA) trial, researchers reported here at the European League Against Rheumatism (EULAR) Congress 2012.

ADACTA, sponsored by Hoffman-La Roche, was a multicenter, randomized, double-blind, 24-week study designed specifically to test superiority of tocilizumab (TCZ) over adalimumab in patients with RA of more than 6 months' duration who were intolerant of methotrexate or for whom continued treatment with methotrexate was inappropriate, said Cem Gabay, MD, PhD, during a press conference.

Until now, the EULAR recommendation has been to use an anti-TNF agent as first-line therapy, said Dr. Gabay, from University Hospitals of Geneva, Switzerland. "But according to these data…it might be considered to use an anti-IL6 — tocilizumab — rather than an anti-TNF."

However, although the results are "interesting," they are also "controversial," EULAR scientific chairperson Xavier Mariette, MD, PhD, from Hôpital Bicêtre in Paris, France, told Medscape Medical News.

The study included a total of 325 patients with RA who were all previously treated with methotrexate and were naive to biologic therapy.

Patients were randomly assigned to intravenous TCZ, 8 mg/kg (n = 163), every 4 weeks plus placebo subcutaneous adalimumab (ADA), or subcutaneous ADA, 40 mg (n = 162), every 2 weeks (plus placebo intravenous TCZ) for 24 weeks.

The primary endpoint was mean change from baseline in the Disease Activity Score of 28 joints (DAS28) at 24 weeks.

The percentage of patients achieving a 20%, 50%, and 70% improvement in swollen and tender joints according to American College of Rheumatology criteria (ACR20/50/70 response rate) was also measured.

Baseline characteristics of the TCZ and ADA treatment groups were similar, with a mean age of 54.4 and 53.3 years, a mean RA duration of 7.3 and 6.3 years, and a mean DAS28 of 6.72 and 6.76, respectively.

At 24 weeks, the mean change in DAS28 from baseline was significantly greater with TCZ than with ADA (change, -3.3 vs -1.8; P < .0001), as was the percentage of patients in DAS28 remission (39.9% vs 10.5%; P < .0001).

TCZ was also superior to ADA in achieving low disease activity (51.5% of patients vs 19.8%, P < .0001) and ACR20, ACR50, and ACR70 responses (65.0% vs 49.4%, 47.2% vs 27.8%, and 32.5% vs 17.9%, respectively; P < .01).

From 8 weeks on, a numeric difference was also seen in favor of TCZ in erythrocyte sedimentation rate and patient global assessment.

There was "no specific safety signal" with TCZ therapy, said Dr. Gabay, with similar rates of adverse events (82.1% with TCZ vs 82.7% with ADA), serious adverse events (11.7% with TCZ vs 9.9% with ADA), and serious infections (3.1% in both groups).

Changes in laboratory values, including elevations in aminotransferase and low-density lipoprotein cholesterol levels and reductions in neutrophil counts, occurred in both groups, with the proportion of patients with abnormal values higher in the TCZ group, he reported.

Although 2 patients died, both in the TCZ group, 1 death was deemed unrelated (due to an illicit drug overdose), and the other, a sudden death on day 93 of the study, was "possibly related." The 56-year-old man had multiple comorbid conditions, including cardiovascular disease, hypertension, overweight, and smoking, Dr. Gabay said.

Asked to comment on the findings, Dr. Mariette said, "it's not completely fair" to have chosen adalimumab as the comparator.

"Everybody knows adalimumab works much better in combination with methotrexate than in monotherapy," he told Medscape Medical News.

"It would have been better either to compare the combination methotrexate plus tocilizumab or adalimumab, or maybe another anti-TNF agent which works better in monotherapy — etanercept for example."

But Dr. Gabay said that although adalimumab is ideally prescribed in combination with methotrexate, this often not the case in real life.

"For patients who need to be treated with monotherapy, I think this is an important message," he said. "It is clear that adalimumab works better when it is given in combination but if you look at different registries that's not how it is done for multiple reasons — sometimes patients are intolerant of methotrexate. So, roughly one third of patients on adalimumab are treated with monotherapy. This is real life. There is clearly a discrepancy between what we teach or what we would like and what is going on."

Dr. Gabay disclosed that he is a consultant for Roche, Abbott, Merck, UCB, Pfizer, Novartis, and Amgen and is on the Speakers Bureau of Roche, Abbott, Merck, UCB, Pfizer, BMS, Merckserono, Novartis, and Amgen. Several of Dr. Gabay's coauthors are employees and shareholders of Roche. Dr. Mariette has disclosed no relevant financial relationships.

European League Against Rheumatism (EULAR) Congress 2012. Abstract #LB0003. Presented June 6, 2012.

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