Among patients with rheumatoid arthritis (RA), outcomes at 78 weeks were similar for those who took infliximab (INF) for 52 weeks before switching to the biosimilar SB2, for those who continued infliximab, and for those who took SB2 for the entire treatment period, a study found.
Josef S. Smolen, MD, professor of internal medicine at the University of Vienna; chairman, Department of Rheumatology, Vienna General Hospital; and chairman, 2nd Department of Medicine, Center for Rheumatic Diseases, Hietzing Hospital, Vienna, Austria, and colleagues report their findings online October 17 in Annals of the Rheumatic Diseases.
The novel parallel-arm study design enabled the researchers to compare the effects of switching from infliximab to SB2 with both a continuous SB2 arm and a parallel, continuing reference infliximab arm. Dr Smolen told Medscape Medical News the complex study design enabled researchers to determine that efficacy, safety, and immunogenicity were similar among all three groups up to week 78.
This is seen as relevant to the way SB2 is likely to be used in clinical practice, and Dr Smolen said the study provides reassuring data to support the safety and efficacy of switching a patient with RA from infliximab to SB2.
“The data presented in the study that biosimilars have comparable efficacy and safety are encouraging and in line with other recently published studies,” Bharat Kumar, MD, clinical assistant professor of internal medicine, University of Iowa Carver College of Medicine, Iowa City, told Medscape Medical News.
Dr Kumar said that he was initially “taken aback” by the unusual study design. “The more I thought about it, the more I saw that it closely resembles what we would do in clinic with someone who was started on an originator biological then switched over. This type of research protocol makes almost a blinded simulation for the real clinic situations, which makes the study even stronger,” he said.
Dr Smolen said he expects this trial design to become more widely used in studies of biosimilars because it is “reassuring for rheumatologists and patients.”
“The objectives of the present transition-extension period (described as transition period hereafter) of the phase III study were to investigate whether individuals on INF could be readily switched to SB2 without major concerns and whether comparable efficacy, safety and immunogenicity were maintained after the switch when compared with both ongoing reference INF as well as SB2,” the authors explain.
The study enrolled 584 patients aged 18 to 75 years with moderate to severe RA despite taking methotrexate. The researchers randomly assigned patients in a 1:1 ratio to receive SB2 (n = 291) or infliximab (n = 293) at weeks 0, 2, and 6, then every 8 weeks until week 46. Patients wo had been receiving infliximab were re–randomly assigned at week 54 to switch to SB2 (n = 94) or continue infliximab (n = 101). Patients originally randomly assigned to SB2 continued that drug (n = 201). Treatment continued to week 70.
Efficacy was assessed by using American College of Rheumatology (ACR) 20, 50, and 70 response criteria; the disease activity score in 28 joints; European League Against Rheumatism (EULAR) responses; the clinical disease activity index (CDAI); and the Simplified Disease Activity Index (SDAI) scores. The CDAI and SDAI were calculated post hoc.
Efficacy was similar for the three groups between weeks 54 and 78: ACR20 scores were 63.5% to 72.3% for those receiving infliximab who were switched to SB2, 66.3% to 69.4% for those receiving continuous infliximab, and 65.6% to 68.3% for those receiving continuous SB2. EULAR responses were also similar.
Treatment-related side effects were also similar in the three treatment groups: 36.2% for infliximab switched to SB2, 35.6% for continuous infliximab, and 40.3% for continuous SB2. Serious adverse effects were low and similar across the groups.
Immunogenicity, assessed as development of serum antidrug antibodies and neutralizing antibodies, was similar across all three groups.
“SB2, an INF biosimilar, maintained comparable efficacy, safety and immunogenicity up to 78 weeks, even after switching from the originator INF. Our results suggest that the clinical profile of SB2, when administered long term or when switched from INF, is comparable with INF,” the authors conclude.
Dr Kumar warned against overinterpretation of the data. “Biosimilars are not ‘generic’ versions of biologic agents,” he said. “They are distinct molecules, and even though providers can consider switching one for another, it doesn’t necessarily mean that patients are getting the same product. We should focus not only on bringing these new biologic agents and biosimilars to market but also on ensuring that patients and physicians have access to information, so that they can make these decisions.”
Dr. Kumar added, “Based on these data, I would be comfortable in switching from infliximab to this biosimilar. It’s important to note that this study only examined infliximab and SB2. Since every biosimilar has unique properties, it’s difficult to generalize the results to all biologics and biosimilars. Similarly, RA is, in actuality, more than one disease. I would like to see studies seeing whether there is equivalent efficacy and safety in different subsets, like people who have RF [rheumatoid factor] and CCP [cyclic citrullinated peptide] antibodies vs those who don’t. I also want to see studies in early RA. The more that we delay treatment, the harder it becomes to treat.”
The study was funded by Samsung Bioepis. Dr Smolen reports receiving grant/research support from AbbVie, Janssen, MSD, Pfizer, Roche, and UCB and consultant fees from AbbVie, Amgen, AstraZeneca, Astro-pharma, Celgene, GSK, Janssen, Lilly, Medimmune, MSD, Novartis-Sandoz, Novo Nordisk, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB. Other authors report grants, research support, or consultant fees from Samsung Bioepis, AbbVie, and Samsung Bioepis. Two authors are employees of Samsung Bioepis and own stock in Samsung Biologics. Dr Kumar has disclosed no relevant financial relationships.
Ann Rheum Dis. Published online October 17, 2017. Full text
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