Patients with RA were randomized to four treatment arms: The sequential monotherapy and step-up therapy arms started with methotrexate and then switched to or added other therapies; the other two arms started with initial combination therapy that included methotrexate and either sulfasalazine plus prednisone, or methotrexate and infliximab. The combination therapies could be tapered to monotherapy if there was sufficient clinical response. All patients were treated to target over the 10 years, with the goal of a DAS score of 2.4 or lower. The average age of patients was 54; about two-thirds were women and one-third were smokers. There were 72 deaths within the RA population during the study years.
Dr. Markusse reported that there was no increased mortality in RA patients compared with the general population, and that the risk factors for increased mortality, such as age, male gender, smoking and functional disability, are known risk factors in the general population. “Survival in this study can be associated with disease suppression as the result of treat-to-target strategy,” she said.
Some attendees at the presentation questioned the trial design, suggesting that with only 72 reported deaths, the study lacked sufficient power. Another attendee noted that patients with risk factors had been excluded from the RA group, whereas patients with risk factors had not been excluded from the general population comparison group.
Ankylosing Spondylitis Therapy
Dominque L. Baeten, MD, PhD, reported results of a Phase 3 trial (Abstract 819) that evaluated secukinumab, an anti-IL-17A monoclonal antibody biologic drug. Dr. Baeten, of the Academic Medical Centre/University of Amsterdam, said the trial demonstrated that secukinumab “provides rapid, significant, and sustained improvement in the signs and symptoms of active AS and is the first anti-IL-17A monoclonal antibody to demonstrate efficacy in Phase 3 clinical trials in ankylosing spondylitis [AS].”
The 371 patients in the trial, who had AS for an average of 6.5 to 8.3 years, were randomized to three treatment arms: intravenous (IV) secukinumab in 10 mg/kg doses at Weeks 0, 2 and 4, followed by subcutaneous secukinumab at 75 mg doses every four weeks; the same as the first arm except for 150 mg doses of secukinumab instead of 75 mg doses; or placebo on the same IV and subcutaneous schedule. Twenty-seven percent of the patients had had an inadequate response to anti-TNF agents prior to inclusion in the trial.
At Week 1, Dr. Baeten said, there was a statistically significant response in the treatment groups, showing the rapid onset of action, with significant improvements in ASAS40, hsCRP, ASAS5/6 and BASDAI. Treated patients had a significantly higher ASAS20 response at Week 16 with both treatment protocols. The improvements were sustained through 52 weeks.
