Study Finds Switching Patients to Biosimilar Infliximab Safe and Effective in IBD

No differences in drug levels or disease activity were found when adult patients with inflammatory bowel disease (IBD) were switched from originator infliximab (Remicade) to a biosimilar infliximab (Inflectra) as part of routine care, according to the results of a Dutch study published in Alimentary Pharmacology & Therapeutics. Switching to the biosimilar and performing therapeutic drug monitoring as part of routine care optimizes infliximab therapy efficiently and makes it more cost effective, the authors conclude.

The study, conducted by E.M.H. Schmitz, PhD, and colleagues, followed 133 patients with IBD (64% had Crohn’s disease [CD]; 36% had ulcerative colitis [UC]) for 12 months. All patients had been receiving innovator infliximab therapy for a median of 52 months before the switch to biosimilar. Half of the patients received concomitant immunosuppressive therapy. The researchers took blood samples just before the first, second, fourth, and seventh infusion of the biosimilar and measured infliximab trough levels, antibodies to infliximab (ATI), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). The investigators also calculated disease activity scores using the Crohn’s disease activity index for patients with CD and the Truelove-Witts disease activity index for patients with UC.

Before the switch to biosimilar infliximab, the investigators found widely varying infliximab levels (median, 3.5µg per mL). ATI were detected in 6% of patients. Most patients were in remission or had mild disease (CD, 82%; UC, 90%). After switching to the biosimilar, 26% of patients (26% CD; 27% UC) discontinued therapy within 12 months, mostly because of subjective higher disease activity (9%) and adverse events (AEs, 9.8%). AEs included general malaise and fatigue, arthralgia, skin problems, and infusion reactions. There were no differences in levels of infliximab or CRP or disease activity between the 4 time points (P ≥0.0917).

Nine percent of the cohort experienced higher disease activity. In the majority of cases, however, complaints of higher disease activity were not shown objectively with higher disease activity scores or increased CRP levels. Increased disease activity was only shown objectively in 2 patients.

In 2 cases, patients also had high disease activity on infliximab innovator therapy. Finally, 3.8% of the cohort discontinued biosimilar therapy because they were in remission, 1 patient temporarily stopped infliximab therapy because she was expecting to go into labor, and 2 patients accidently received innovator instead of biosimilar infliximab.

The researchers said that they found that patients with detectable ATI before switching had a relative risk of 3.2 for discontinuation of biosimilar therapy compared with patients with no ATI. “This indicates that patients with autoimmune response to [infliximab] have a statistically significantly higher risk of therapy failure,” they note. “It was shown that antibodies to [infliximab] innovator are highly similar to antibodies to the biosimilar, so these patients would probably also have experienced therapy failure if they would have stayed on innovator therapy.”

The researchers also said that the novelty of biosimilars could induce the nocebo effect (disease worsening due to negative expectations) and noted that the switch to biosimilars was the first such switch in their hospital. “Patients were easily put back on innovator treatment if they had complaints that could possibly be switch-related due to the lack of experience with biosimilars in clinical practice,” they said.

The researchers conclude that biosimilar infliximab is safe and effective. They said the high proportion of discontinuers in their study were mostly due to elective withdrawal or subjective disease worsening.