Switching from SB2 to PF-06438179/GP1111 and back in inflammatory bowel disease: “The Superswitchers”

The introduction of biological therapies based on tumor necrosis factor (TNF) inhibition has revolutionized the management of Crohn's disease (CD) and ulcerative colitis (UC) [ [1] Danese S. Vuitton L. Peyrin-Biroulet L Biologic agents for IBD: practical insights. Nat Rev Gastroenterol Hepatol. 2015; 12: 537-545 Crossref PubMed Scopus (222) Google Scholar ]. The originator of infliximab (IFX) (Remicade®) was the first biologic approved for the treatment of moderate-to-severe forms of inflammatory bowel disease (IBD) in 1998. It showed to be effective in improving several clinical outcomes, while the reduction of surgery and hospitalization rates is debated [ [2] Mao E.J. Hazlewood G.S. Kaplan G.G. et al. Systematic review with meta-analysis: comparative efficacy of immunosuppressants and biologics for reducing hospitalization and surgery in Crohn's disease and ulcerative colitis. Aliment Pharmacol Ther. 2017; 45: 3-13 Crossref PubMed Scopus (158) Google Scholar ]. Following the expiration of the patent of the originator product, several low-cost biosimilars of IFX were rapidly developed. The IFX biosimilar CT-P13 (Inflectra® and Remsima®) was the first to be approved in 2013 by the US Food and Drug Administration and the European Medicines Agency. Equivalence of CT-P13 with the originator was shown both in terms of safety and efficacy [ 3 Fiorino G. Manetti N. Armuzzi A. et al. The PROSIT-BIO cohort: a prospective observational study of patients with inflammatory bowel disease treated with infliximab biosimilar. Inflamm Bowel Dis. 2017; 23: 233-243 Crossref PubMed Scopus (114) Google Scholar , 4 Armuzzi A. Fiorino G. Variola A. et al. PROSIT Investigators. The PROSIT cohort of infliximab biosimilar in IBD: a prolonged follow-up on the effectiveness and safety across Italy. Inflamm Bowel Dis. 2019; 25: 568-579 Crossref PubMed Scopus (46) Google Scholar , 5 Jorgensen K.K. Olsen I.C. Goll G.L. et al. Switching from originator infliximab to biosimilar CT-P13 compared with maintained treatment with originator infliximab (NOR-SWITCH): a 52-week, randomised, double- blind, non-inferiority trial. Lancet. 2017; 389: 2304-2316 Abstract Full Text Full Text PDF PubMed Scopus (586) Google Scholar , 6 Meyer A. Rudant J. Drouin J. et al. Effectiveness and safety of reference infliximab and biosimilar in Crohn disease: a French equivalence study. Ann Intern Med. 2019; 170: 99-107 Crossref PubMed Scopus (73) Google Scholar ]. The second IFX biosimilar that received authorization for the treatment of IBD was SB2 (Flixabi®), closely followed by PF-06438179/GP1111 (Zessly®). As for CT-P13, robust clinical evidence has supported clinicians in increasing their confidence in the use of these biosimilars for IBD treatment [ 7 Fiorino G. Ruiz-Arguello M.B. Maguregui A. et al. Full interchangeability in regard to immunogenicity between the infliximab reference biologic and biosimilars CT-P13 and SB2 in inflammatory bowel disease. Inflamm Bowel Dis. 2018; 24: 601-606 Crossref PubMed Scopus (44) Google Scholar , 8 Macaluso F.S. Fries W. Viola A. The SPOSIB SB2 sicilian cohort: safety and effectiveness of infliximab biosimilar SB2 in inflammatory bowel diseases, including multiple switches. Inflamm Bowel Dis. 2021; 27: 182-189 Crossref PubMed Scopus (28) Google Scholar , 9 McClellan J.E. Conlon H.D. Bolt M.W. et al. The 'totality-of-the-evidence' approach in the development of PF-06438179/GP1111, an infliximab biosimilar, and in support of its use in all indications of the reference product. Therap Adv Gastroenterol. 2019; 121756284819852535 Crossref PubMed Scopus (8) Google Scholar ]. At our center, CT-P13 became available for clinical practice in July 2015, rapidly replacing the originator product; SB2 and PF-06438179/GP1111 became available in August 2018 and June 2020, respectively. Only one IFX biosimilar was available at a time at our hospital. Therefore, each new biosimilar progressively replaced the previous one. All patients who were IFX-naïve were initiated with the newly available biosimilar, while those already on treatment were progressively switched to the newly available biosimilar. From March 2022, for the first time, two biosimilars of IFX - PF-06438179/GP1111 and SB2 – were available at the same time at our center. While safety and effectiveness of switching from the IFX originator to one of its biosimilars have been widely demonstrated, data on multiple switches from one biosimilar to another are more limited [ [10] Ribaldone D.G. Tribocco E. Rosso C. et al. Switching from biosimilar to biosimilar adalimumab, including multiple switching, in crohn's disease: a prospective study. J Clin Med. 2021; 10: 3387 Crossref PubMed Scopus (11) Google Scholar ]. This paucity of clinical data has advised a prudent attitude towards multiple switching from one biosimilar to another [ [11] Fiorino G. Caprioli F. Daperno M. et al. National patients’ association representatives; IG-IBD members. Use of biosimilars in inflammatory bowel disease: a position update of the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD). Dig Liver Dis. 2019; 51: 632-639 Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar ], including returning to a biosimilar previously used in the course of the medical history of an IBD patient.