P1014 Anti-TNF-alpha biosimilar cross and reverse-switching in pediatric IBD: Preliminary real-world data from the SIGENP IBD Working Group
Authors: Dipasquale V , Fioretti L , Morello R , Pochesci S , Scarallo L , Graziano F , Citrano M , Lionetti P , Romano C 
Published: January 2025

Abstract

Background
Due to the increasing number of pediatric IBD patients receiving anti-TNF-alpha, multiple switching between biosimilars has become part of everyday clinical practice, although it is not yet officially recommended. A multicenter, nationwide retrospective study to determine the safety and effectiveness of multiple switching is currently underway within the IBD Working Group of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP).

Methods
Data from all pediatric IBD patients on anti-TNF-alpha treatment (IFX, ADA) who made one or more switches from one biosimilar to another (cross-switch) or from one biosimilar to the originator (reverse-switch) from 2013 to present have been collected. Safety was the primary study objective. These data are preliminary as data collection is still ongoing in additional centers.

Results
To date, three centers have collected data on 89 patients who underwent at least one cross- or reverse-switch 13.7 months (7-23.5) after starting biologic therapy: 51 with IFX (significantly more for UC and IBDU patients than CD patients, p&lt;0.01) and 38 with ADA (significantly more in CD than in UC/IBDU patients, p&lt;0.01). Twenty-one (23.6%) patients were switched twice, four (4.5%) three times, at 5.2 months (2-14.7) and 16.4 months (5.1-18.7), respectively since the previous switch. 84 were cross-switches and 5 were reverse-switches. The switch was non-medical in most cases (n=86, 89%) and medical in the remaining cases (due to adverse events). The median follow-up time was 3.6 years (2.2–6.4) from the start of biologic therapy. An acute infusion reaction occurred in 6/89 (6.7%), 1/21 (4.8%) and 1/4 (25%) patients after the first, second and third switches, respectively. Multiple switching was associated with a relapse in 2/89 (2.2%) and 2/21 (9.5%) after the first and second switching, respectively. No between-group differences in reactions or flares were noted between IFX and ADA.

Conclusion
Multiple switching biosimilars are a reality in the current practice in pediatric IBD. This practice does not appear to have any effect on the course of the disease, but further data are pending.

References
de Ridder L, Assa A, Bronsky J, et al. Use of biosimilars in pediatric inflammatory bowel disease: an updated position statement of the pediatric IBD Porto Group of ESPGHAN. J Pediatr Gastroenterol Nutr. 2019;68:144–153. doi:10.1097/MPG.0000000000002141
Mysler, E., Azevedo, V.F., Danese, S. et al. Biosimilar-to-biosimilar switching: what is the rationale and current experience?. Drugs 81, 1859–1879 (2021). https://doi.org/10.1007/s40265-021-01610-1
Cohen, H.P., Hachaichi, S., Bodenmueller, W. et al. Switching from one biosimilar to another biosimilar of the same reference biologic: a systematic review of studies. BioDrugs 36, 625–637 (2022). https://doi.org/10.1007/s40259-022-00546-6
Dipasquale V, Pellegrino S, Ventimiglia M, Cucinotta U, Citrano M, Graziano F, Cappello M, Busacca A, Orlando A, Accomando S, Romano C; Sicilian Network for Inflammatory Bowel Disease. Real-life experience of infliximab biosimilar in pediatric-onset inflammatory bowel disease: data from the Sicilian Network for Inflammatory Bowel Disease. Eur J Gastroenterol Hepatol. 2022 Oct 1;34(10):1007-1014. doi: 10.1097/MEG.0000000000002408
Dipasquale V, Pellegrino S, Ventimiglia M, Citrano M, Graziano F, Cappello M, Busacca A, Orlando A, Accomando S, Romano R; Sicilian Network for Inflammatory Bowel Disease. Adalimumab biosimilar in pediatric inflammatory bowel disease: a retrospective study from the Sicilian Network for Inflammatory Bowel Disease (SN-IBD). Healthcare (Basel). 2024 Feb 4;12(3):404. doi: 10.3390/healthcare12030404
Dipasquale V, Cicala G, Spina E, Romano C. Biosimilars in Pediatric Inflammatory Bowel Diseases: A Systematic Review and Real Life-Based Evidence. Front Pharmacol. 2022 Mar 17;13:846151. doi: 10.3389/fphar.2022.846151