Biosimilar CT-P13 Matches Infliximab for Crohn's Disease

Janis C. Kelly

December 12, 2018

Crohn's disease (CD) can be treated equally well with infliximab or with the biosimilar CT-P13, the choice can be based on cost alone, and this equivalence might expand patient access to more effective treatment, researchers report.

Antoine Meyer, MD, Caisse Nationale de l'Assurance Maladie, Paris, and Hôpital Bicêtre, Le Kremlin-Bicêtre, France, and colleagues published their findings online December 11 in the Annals of Internal Medicine.

"Our nationwide observational cohort study of infliximab-naive patients with CD demonstrates equivalent effectiveness of [infliximab] and CT-P13. The [hazard ratio; HR] and 95% [confidence interval; CI] (HR, 0.92; CI, 0.85 - 0.99) were situated within the predefined equivalence margins (0.80 to 1.25) and no significant differences were observed between the two groups in terms of serious infections, tuberculosis, and solid or hematologic cancer," the researchers write.

"This study, which ... [included] ... more than 5000 patients with Crohn disease who were treated with infliximab, demonstrates that the effectiveness of CT-P13 is equivalent to that of the original product in infliximab-naive patients," Ole Haagen Nielsen, MD, DMSc, from the University of Copenhagen Herlev Hospital, Herlev, and Mark Andrew Ainsworth, MD, PhD, from Odense University Hospital, Odense, both in Denmark, write in an accompanying editorial.

"These results suggest that switching to biosimilars should not cause concerns about effectiveness or safety, and thus it seems possible to define levels of structural similarity that will ensure the absence of any clinically significant differences in safety and efficacy between the original product and the biosimilar," they add.

The researchers note that this study assessed outcomes in "real-life" settings, not with the highly selected patients typically studied in clinical trials. They write, "Over the past 40 years, new drug approval has been based on randomized, double-blind, controlled trials. However, patients included in these trials are highly selected. One study showed that only 34% of patients with CD seen in clinical practice can be included in trials. Studies such as ours assess real-life effectiveness by including all patients receiving treatment with long-term follow-up."

The researchers conducted a nonrandomized, observational, comparative equivalence study in 5050 infliximab-naive patients with Crohn's disease from the French nationwide Systéme National des Données de Santé administrative database. The analysis included 2551 patients on infliximab and 2499 patients on CT-P13 treated between March 1, 2015, and November 30, 2016. The primary outcome was a composite endpoint that included CD-related surgery, all-cause hospitalization, and reimbursement of another biologic therapy.

Because the database does not include all clinical data, the researchers were not able to calculate indices such as the Harvey-Bradshaw or Crohn's Disease Activity Index; they used proxies to estimate disease severity. Treatment was considered equivalent when the treatment HR and CI were situated within equivalence margins of 10%. Median follow-up was 366 days for infliximab and 286 for CT-P13.

The analysis showed no significant difference in 6-, 12-, and 18-month cumulative incidence of the primary outcome. Multivariable analysis showed the two treatments to be equally effective and to have similar safety profiles.

The researchers conclude, "[O]ur observational study of real-life data suggests that effectiveness of CT-P13 is equivalent to that of [the reference product] in infliximab-naive patients. No difference was observed in terms of safety outcomes. The choice between the two products can therefore be based on cost only."

Concern about biosimilar equivalence arises from the importance of biologics in the treatment of Crohn's disease and other inflammatory disorders and from differences in the approval process for biosimilars compared with generic versions of conventional drugs. Nielsen and Ainsworth explain that infliximab and related drugs have transformed the Crohn's disease treatment paradigm from symptom control to healing the mucosa and preserving intestinal function, while also driving up healthcare costs. Regulatory focus on biosimilars as the patents for original biologics expire reflects these cost concerns.

The editorialists write that the framework for biosimilar approval is based on the assumption that for two products with similar molecular structure and bioavailability, "information on the safety and efficacy of one can be extrapolated to the other, making replication of large and expensive safety and efficacy studies unnecessary."

This is complicated by the fact that biosimilars cannot be engineered as identical copies as a result of their structural complexity and the use of genetically modified cell culture to produce them. The infliximab–CT-P13 study was done in part to address concerns that these differences might affect efficacy or safety.

"From the perspectives of patients and physicians, the concept of biosimilars seems to be working — the available data indicate no clinically relevant differences in safety and efficacy between infliximab and CT-P13 (the first biosimilar to enter the market).... This study...demonstrates that the effectiveness of CT-P13 is equivalent to that of the original product in infliximab-naive patients," Nielsen and Ainsworth write.

"These results suggest that switching to biosimilars should not cause concerns about effectiveness or safety, and thus it seems possible to define levels of structural similarity that will ensure the absence of any clinically significant differences in safety and efficacy between the original product and the biosimilar," they conclude.

The authors and editorialists have disclosed no relevant financial relationships.

Ann Intern Med. Published online December 11, 2018. AbstractEditorial

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