November 28, 2016
By David Douglas
NEW YORK (Reuters Health) - In patients with rheumatoid arthritis (RA), certolizumab pegol with methotrexate is not superior to adalimumab plus methotrexate, according to a head-to-head comparison.
In a November 15 online paper in The Lancet, Dr. Josef S. Smolen of the University of Vienna, Austria, and colleagues note that no trials have made direct comparisons. And none have investigated directly switching to a second TNF inhibitor following an inadequate response to the first.
"Hitherto," Dr. Smolen told Reuters Health by email, "comparisons between different TNF inhibitors regarding efficacy and safety were only made indirectly, such as by meta-analyses, but never before in head-to-head studies."
To do so, the researchers randomized 915 patients from 151 centers worldwide to receive certolizumab pegol (Cimzia, UCB Pharma) plus methotrexate or adalimumab plus methotrexate.
At 12 weeks, there was no significant difference in ACR20 response between certolizumab and adalimumab groups (69% versus 71%). At two years, this was also the case for low disease activity as determined by the Disease Activity Score 28-erythrocyte sedimentation rate (35% versus 33%).
At 12 weeks, 65 nonresponders to certolizumab were switched to adalimumab. After a further 12 weeks, 40 (62%) showed a response. A corresponding switch to certolizumab following non response to adalimumab in 57 patients led to a response in 33 (58%).
After switching, and within 70 days of the last dose of initial study drug, no serious infection events were reported in either population.
Overall, over the course of the study, 75% of the certolizumab group and 74% of the adalimumab patients experienced treatment-emergent adverse events. Three deaths were reported in each group.
Summing up, Dr. Smolen said the study showed "similar results in all outcomes for certolizumab pegol and adalimumab. Importantly, many patients who had no improvement on one of the TNF inhibitors within 12 weeks and then switched to the other one experienced significant clinical effects, revealing that even primary anti-TNF failures can respond to a second TNF inhibitor and that the 3-month time point, indeed, is an excellent time point to judge improvement and make informed treatment decisions regarding continuation or change of therapy."
In email to Reuters Health, Dr. Tore K. Kvien of Diakonhjemmet Hospital, Oslo, Norway agreed.
Dr. Kvien, coauthor of an accompanying editorial, pointed out, "The first important message is that no difference was found for the primary endpoint . . . even though the study was designed to examine the superiority of certolizumab over adalimumab."
"Secondly," added Dr. Kvien, "the study supports that switching from one TNF inhibitor to another TNF inhibitor is also effective and that immediate switch at 12 weeks without a washout period did not provide major safety issues."
UCB Pharma funded the study and a number of authors have ties to the company.
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