Systematic Review Does Not Find Significant Risk Associated With a Single Switch

As more biosimilars make their way to patients in the United States and Europe, stakeholders seek reassurance on switching to these products. A newly published systematic review sought to investigate the safety and efficacy of switching between reference and biosimilar infliximab in patients with inflammatory disorders.

The review, funded by Janssen, relies on English-language journal articles on biosimilar infliximab published between 2004 and 2018 that were identified through the MEDLINE database. The 36 studies eligible for inclusion all reported efficacy, safety, or immunogenicity data. Additionally, 34 abstracts from 2012 to 2017 were sourced from major meetings using the EMBASE database.

In total, 13 publications presented results from 6 randomized controlled trials of SB2 (Renflexis), CT-P13 (Inflectra), and BOW015 (an unapproved product developed by Epirus), and all 6 were single-transition studies:

• A 78-week SB2 transition trial in patients with rheumatoid arthritis (RA) did not find a change in safety, efficacy, or immunogenicity in patients who switched from the reference to SB2 versus those who remained on the reference.
• A Japanese study reporting a single-arm open-label extension of a 54-week study comparing CT-P13 with its reference in patients with RA found that the incidence of adverse events (AEs) was comparable between patients who did and did not switch, though AEs leading to discontinuation were higher among those who switched. At week 134, the number of patients positive for antidrug antibodies (ADAs) was comparable between groups.
• The open-label extensions of PLANETRA and PLANETAS, studies that have been described in detail, assessed switches to CT-P13 in patients with RA and ankylosing spondylitis (AS), respectively. PLANETRA found similar efficacy, incidence of treatment emergent AEs, and numbers of patients with ADAs at week 102 among those who did and did not switch. PLANETAS found similar efficacy between those who did and did not switch. The incidence of treatment emergent AEs was lower in patients with AS who did not switch, but no statistical comparisons were performed. The number of patients who were positive for ADAs at week 102 was similar in both groups.
• A phase 3 study of BOW015 found similar efficacy and measures of disease activity and disability among patients with RA who switched to the biosimilar and those who did not switch.
• NOR-SWITCH, which has also been described in detail, found similar disease worsening between patients who switched to CT-P13 and those who remained on reference infliximab during a 52-week follow-up period. The study was not powered to show noninferiority in individual disease states of RA, spondyloarthritis, psoriatic arthritis, ulcerative colitis, Crohn disease (CD), and plaque psoriasis.

An additional 53 publications report switching from reference infliximab to biosimilars in observational studies, but no studies report switching among biosimilars. Most uncontrolled studies did not report changes in safety, efficacy, or immunogenicity after a switch: “While several uncontrolled studies did report high rates of failure or discontinuation after transition, this was not consistently observed across studies,” write the authors.

Finally, 2 case studies reported lichenoid drug eruption and serum sickness-like disease in patients with CD and RA after switching to CT-P13, and a case series of 3 patients with Behçet disease reported loss of response after a switch to CT-P13. An additional case series reported maintained safety and efficacy in 9 patients with inflammatory bowel disease who switched to CT-P13.

“Overall, the evidence presented is this review is generally supportive of the safety and efficacy of one‐time switching between reference and biosimilar infliximab. However, after conducting this systematic review of the literature, we concluded that there was insufficient data to perform a meaningful meta‐analysis at this time,” conclude the authors. “Additionally, no studies have investigated multiple switching scenarios or switching between biosimilars, which may be representative of real‐world situations.”

Reference

Feagan BG, Lam G, Ma C, Lichtenstein GR. Systematic review: efficacy and safety of switching patients between reference and biosimilar infliximab.Aliment Pharmacol Ther.2018;1-10. doi: 10.1111/apt.14997.