5 Things to Know About Biosimilars and Inflammatory Bowel Disease

Last week, the European Crohn's and Colitis Organisation held its 13th annual congress in Vienna, Austria. At the meeting, researchers presented new data on using biosimilar anti—tumor necrosis factor (TNF) therapies in treating Crohn disease (CD) and ulcerative colitis (UC), 2 manifestations of inflammatory bowel disease (IBD).

1. New data support switching to a biosimilar in CD and UC.

The NOR-SWITCH trial—a 52-week double-blind noninferiority trial that has become the basis on which the case for switching patients to biosimilars has been made—demonstrated that switching from reference infliximab to a biosimilar infliximab was noninferior to continued treatment with the reference product in terms of efficacy, safety, and immunogenicity. However, the trial wasn’t powered to demonstrate the noninferiority of the biosimilar in individual disease states, including CD and UC.

Last week’s presentation of IBD-specific data¹ from the study’s 26-week open label extension could help to ease some prescribers' concerns about switching patients with IBD to a biosimilar; among patients with CD and UC who received a biosimilar therapy without interruption versus patients who switched between the reference and the biosimilar, the study showed no difference in terms of efficacy, safety, and immunogenicity.

2. Switching back to an originator product appears to be well tolerated.

In Hungary, all infliximab-naïve patients with IBD and exposed patients with at least a 1-year drug holiday were required to use biosimilar infliximab when initiating treatment or to switch to biosimilar infliximab. However, a change in the nation’s health system policy mandated a switch back to the reference drug. This change provided an opportunity to study the short-term drug sustainability, safety, and immunogenicity profile of a reversed switch in a consecutive multicenter real-life cohort. Follow-up is ongoing, but only 1 patient did not tolerate the first infusion of the reference infliximab; that patient experienced an infusion-related reaction.²

3. Even if switching is well tolerated, patients remain concerned.

In a French study³ in 117 patients whose IBD was in clinical remission for at least 6 months, researchers provided each patient with individualized information about biosimilars and the possibility of switching from reference infliximab to a biosimilar. Most (97%) consented to the switch.

During follow-up, 12.4% of switched patients experienced a loss of response, but most of these patients regained clinical remission after dose optimization, and some discontinued therapy after achieving deep remission. A significant improvement in fatigue was demonstrated in those who switched, and there was no difference in patient perspective as measured by the Beliefs about Medicines Questionnaire. Despite these findings, another questionnaire showed that patients were still concerned about the possibility of their therapy being switched, especially if the switch were up to their pharmacist.

4. Using immunomodulators can help prevent the development of anti-drug antibodies to both biosimilar and originator anti-TNF drugs.

UK researchers presented data from a 3-year prospective observational study⁴ of 1601 patients with CD who received biosimilar infliximab, the reference infliximab, or adalimumab. They found similar rates of primary nonresponse, remission, and immunogenicity across the 3 groups. The use of immunomodulators in all 3 groups reduced the risk of immunogenicity. The investigators said that these data point to opportunities to optimize the management of anti-TNF therapies and to prevent treatment failure in patients with CD.

5. Using biosimilar infliximab in pediatric and adolescent patients with CD could improve cachexia.

CD in some pediatric and adolescent patients involves cachexia, which manifests as malabsorption, nutritional deficiencies, osteopenia, sarcopenia, and growth failure. In an animal model,⁵ using biosimilar infliximab significantly improved cachexia, demonstrating significantly lowered mortality, tempered weight loss, and preserved appetite. Adalimumab had similar results. The investigators in this study say that anti-TNFs should be considered for the treatment of pediatric or adolescent patients with CD who have severe wasting conditions.

References

1. Jørgensen KK, Goll GL, Sexton J, et al. Long-term efficacy and safety of biosimilar infliximab (CT-P13) after switching from originator infliximab: explorative subgroup analyses in IBD from the NOR-SWITCH EXTENSION trial. Presented at the 13th Congress of the European Crohn’s and Colitis Organisation, February 14 to 17, 2018; Vienna, Austria. Abstract P483. https://www.ecco-ibd.eu/publications/congress-abstract-s/abstracts-2018/item/p483-long-term-efficacy-and-safety-of-biosimilar-infliximab-ct-p13-after-switching-from-originator-infliximab-explorative-subgroup-analyses-in-ibd-from-the-nor-switch-extension-trial.html.

2. Pierik MJ, van der Meulen-de Jong AE, Bloemsaat-Minekus JPJ, van Megen YJB, Dijkstra G. Switching from the originator infliximab to biosimilar CT-P13 did not change the quality of life and clinical efficacy for IBD patients in stable remission in daily clinical practice (interim analysis). Presented at the 13th Congress of the European Crohn’s and Colitis Organisation, February 14 to 17, 2018; Vienna, Austria. Abstract P464. https://www.ecco-ibd.eu/publications/congress-abstract-s/abstracts-2018/item/p464-switching-from-the-originator-infliximab-to-biosimilar-ct-p13-did-not-change-the-quality-of-life-and-clinical-efficacy-for-ibd-patients-in-stable-remission-in-daily-clinical-practice-interim-analysis.html.

3. Petitdidier N, Gagniere C, Rentien AL, et al. Patients’ perspectives on switching from reference infliximab to CT-P13 biosimilar in patients with inflammatory bowel disease: a 12-month prospective observational cohort study. Presented at the 13th Congress of the European Crohn’s and Colitis Organisation, February 14 to 17, 2018; Vienna, Austria. Abstract P528. https://www.ecco-ibd.eu/publications/congress-abstract-s/abstracts-2018/item/p528-patients-x2019-perspectives-on-switching-from-reference-infliximab-to-ct-p13-biosimilar-in-patients-with-inflammatory-bowel-disease-a-12-month-prospective-observational-cohort-study.html.

4. Kennedy NA, Heap G, Hamilton B, et al. Clinical effectiveness, safety and immunogenicity of anti-TNF therapy in Crohn’s disease: 12-month data from the PANTS study. Presented at the 13th Congress of the European Crohn’s and Colitis Organisation, February 14 to 17, 2018; Vienna, Austria. Oral presentation OP031. https://www.ecco-ibd.eu/publications/congress-abstract-s/abstracts-2018/item/op031-clinical-effectiveness-safety-and-immunogenicity-of-anti-tnf-therapy-in-crohn-x2019-s-disease-12-month-data-from-the-pants-study.html.

5. Hahm KB, Han YM, Park JM, Kang EA. Adalimumab and infliximab biosimilar ameliorated cachexic syndrome of Crohn disease. Presented at the European Crohn's and Colitis Organisation Congress 2018 meeting, February 14 to February 17, 2018; Vienna, Austria. Abstract P089. www.ecco-ibd.eu/publications/congress-abstract-s/abstracts-2018/item/p089-adalimumab-and-infliximab-biosimilar-ameliorated-cachexic-syndrome-of-crohn-disease.html.