A long-term observational study suggests a non-medical switch from infliximab to SB2 is “a feasible option” for patients with inflammatory bowel diseases (IBD).
An 80-week observational study of 144 patients with inflammatory bowel disease (IBD) switched from the reference infliximab to biosimilar SB2 found no “medically meaningful” changes in indicators of effectiveness or safety.
Until the start of the study, the patients had been treated with the infliximab originator (Remicade), a monoclonal antibody to tumor necrosis factor alpha (TNF) used for over 20 years to treat IBD. It was the first biologic approved to treat IBD in the United States and Europe. The biosimilar SB2 (Renflexis, Flixabi) was approved by the European Medicines Agency (EMA) in 2016 and the FDA in 2017.
According to the researchers, data on SB2 in patients with IBD are scarce compared with those on CT-P13, the first infliximab biosimilar approved by the FDA in 2016. They found only 2 previous reports on SB2 in IBD, both from the same cohort of patients in Italy.
The observational study followed 94 patients with Crohn disease (CD) and 50 with ulcerative colitis (UC) at an outpatient IBD clinic in Germany. Each patient, following counseling with a physician, underwent a non-medical switch from the reference product to SB2. Outcome measures, including disease activity, C-reactive protein (CRP) levels, and adverse events, were recorded at 24, 48, and 72 weeks.
Disease activity, as measured by Harvey-Bradshaw Index (HBI) in CD and partial Mayo Score (pMS) in UC, remained consistent throughout the SB2 treatment period, the authors said. The mean change from baseline to 72 weeks was -0.4 (2.0) in HBI and 0.1 (1.3) in pMS.
At baseline 69% of patients were in clinical remission, and at week 80, 74% were in clinical remission. At baseline, 21% had mild activity and 10% had moderate activity, compared with 17% and 9% at week 80. No patients had severe activity at baseline or week 80.
Median CRP levels “remained within the normal threshold,” throughout the study period, according to the researchers. Median CRP levels were 2.2 mg/L (interquartile range[IQR], 0.9-5.6) at baseline, 2.3 (IQR, 0.9-7.2) at week 24, 2.3 (IQR, 1.0-7.1) at week 48, and 2.7 (IQR, 0.9-6.1) at week 72.
The authors wrote that “a consistent proportion of patients” were within the therapeutic range of infliximab trough level (TL) of 3-7 µg/ml throughout the study, with 28% in the therapeutic range at baseline, 35% at week 24, 32% at week 48, and 35% at week 72.
At baseline, anti-drug antibodies (ADAs) were detected in 11 patients (9.8%). According to the researchers, the rate of development of ADAs during SB2 treatment was “low and not outside the expected range.” After the switch to SB2, transient ADAs were detected in 3.6% of patients, and persistent ADAs were detected in 6.3% of patients. The authors wrote, “these findings are in line with published data that showed cross-reactivity of ADA to originator infliximab and the biosimilars CT-P13 and SB2 in IBD patients, suggesting full-interchangeability regarding immunogenicity.”
Overall, 27.8% of patients experienced adverse events (AEs), and 7.6% experienced serious AEs during SB2 treatment. The non-severe AEs included infections, abscesses, newly occurring fistulae, infusion reactions, and new-onset rheumatoid or dermatologic diseases. Among serious AEs, 4 malignancies were diagnosed, 4 patients with CD required surgery, 1 patient developed a liver abscess, and another was hospitalized for a severe bronchopulmonary infection.
The authors said the rate of discontinuation in their study (29.2%) was similar to that reported in the previous study they cited of SB2 in patients with IBD (26.1%). Discontinuation due to clinical secondary loss of response occurred in 13.9% of patients, which the authors said was “within the expected range.”Discontinuation due to serious AEs occurred in 6.3% of patients, persistent infusion reactions in 2.8%, and infectious complications in 3.5%. One patient paused treatment due to remission.
First long-term data on switch to SB2
The authors concluded their data on effectiveness and safety of SB2 were “in line with the available results for switching procedures from originator infliximab to the biosimilar CT-P13” and called switching to SB2 “a feasible option” for patients with IBD.
They described their study as significant because it is “the first long-term data over an 18-month follow-up period” on effectiveness, safety, and immunogenicity of a switch from the reference product to SB2 in patients with IBD.
They acknowledged that, as an observational study in a real-life setting, there was no control group remaining on the reference product. Other limitations they noted were that endoscopic evaluation was not possible and fecal calprotectin could not be assessed.
Fischer S, Cohnen S, Klenske E, et al. Long-term effectiveness, safety and immunogenicity of the biosimilar SB2 in inflammatory bowel disease patients after switching from originator infliximab. Therap Adv Gastroenterol. Published online January 14, 2021. doi: 10.1177/1756284820982802.