番茄社区

The biosimilar CT-P13 (Inflectra) showed equivalent efficacy and safety to the anti-tumor necrosis factor (TNF) antibody infliximab (Remicade) in a French health insurance-based study of infliximab-naive Crohn's disease (CD) patients.

With CT-P13 performing similarly to infliximab, the researchers suggested that in real-life practice the choice between the two products could safely be based on cost alone. "Studies such as ours assess real-life effectiveness by including all patients receiving treatment with long-term follow-up," wrote Antoine Meyer, MD, of Caisse Nationale de I'Assurance Maladie in Paris, and colleagues in .

They studied 5,050 CD patients (53.6% female) from 530 French hospitals who were taking infliximab (n=2,551) or CT-P13 (n=2,499) during 2015-2017.

The patients, ages 15 to 55 and older, began treatment in 2015 or 2016. The age groups of 15-24 and 25-34 accounted for 53% of the patients overall. The duration of disease ranged from <6 months (27.2%) to >6 years (29.7%), and most patients (71.4%) had no previous exposure to biologic therapy of any kind. Patient characteristics at cohort entry were well balanced, but with a trend toward more severe CD in the CT-P13 group, the researchers said.

Infliximab was more often prescribed in private hospitals than in university hospitals (33.9% vs 30.9%), while CT-P13 was used less frequently in private hospitals than in university hospitals (21.6% vs 43.6%).

The primary outcome was a composite endpoint of death, CD-related surgery, all-cause hospitalization, and reimbursement for a different biologic. Equivalence was defined as a 95% confidence interval (CI) of the hazard ratio (HR) of CT-P13 vs infliximab in a multivariable marginal Cox model situated within prespecified margins (0.80-1.25).

Overall, 1,147 patients in the infliximab group and 952 in the CT-P13 group met the composite endpoint, which included 838 and 719 hospitalizations, respectively. In a multivariable analysis of the primary outcome, CT-P13 was equivalent to infliximab: HR 0.92 (95% CI 0.85-0.99). No differences in safety outcomes emerged between the two agents for serious infections (HR 0.82, CI 0.6-1.11), tuberculosis (HR 1.10 CI 0.36-3.34]), and solid or hematologic cancer (HR 0.66, CI 0.33-0.32), the team reported.

At 6, 12, and 18 months, the cumulative incidence rates of the primary outcome for the two treatments were 29.6% (95% CI 27.8-31.4), 43.1% (41.2-45.1), and 51.5% (49.6-53.4), respectively, in the infliximab group; and 28.6% (26.9-30.4), 41.6% =(39.7-43.6), and 50.1% (48.1-52.0), respectively, in the CT-P13 group.

Overall, a composite event was reported in 1,147 patients (45.0%), including 838 hospitalizations (32.8%), in the infliximab group and 952 patients (38.1%), including 719 hospitalizations (28.8%), in the CT-P13 group. More than two-thirds (67.6%) of admissions were CD-related.

Research has shown that biosimilars are getting closer to being interchangeable with infliximab for CD and other inflammatory diseases such as rheumatoid arthritis and ankylosing spondylitis.

An by Danish researchers pointed out that while TNF inhibitors have revolutionized the management of CD, the gains made with these biologics have come at considerable cost to patients and the healthcare system, a burden that biosimilars can ease.

"The introduction of biosimilars has resulted in cost savings, and further economic benefits are anticipated as use of these products increases," wrote Ole Haagen Nielsen, MD, DMSc, of University of Copenhagen Herlev Hospital, and Mark Andrew Ainsworth, MD, PhD, DMSc, of Odense University Hospital.

They said that while access to biosimilars will likely expand with positive impacts on worker absenteeism and productivity, the challenges must not be underestimated. Even with the strict requirements for documentation of similarity, pharmacovigilance systems must be able to distinguish between the original product and the biosimilar to allow rapid identification of any signal of impaired safety and efficacy, Nielsen and Ainsworth stated.

In addition, when a patient is switching to a biosimilar or starting therapy with a biosimilar, communication must be open and clear and patient concerns must be addressed. "Most important, to alleviate concerns, healthcare professionals must be proactive in increasing patients' confidence by providing evidence-based information from the growing experience with biosimilars," the editorial notes.

Regarding study limitations, Meyer and co-authors pointed to the absence of full clinical data allowing calculation of indices of disease severity such as the Harvey-Bradshaw Index or Crohn's Disease Activity Index, which necessitated the use of proxies. Additionally, the study used an algorithm to identify CD patients based on the combination of hospitalization and long-term disease codes. Infliximab use was based on prescriptions dispensed, and only infliximab-naive patients were included in the cohort.

The investigators also noted the need for further study to assess the impact of switching from infliximab to CT-P13 (or vice versa). In addition, some hospitals used only the biosimilar, while others, only the original antibody. Another caveat, the researchers said, is that the 95% CI did not contain 1.00, which might suggest superiority for CT-P13 over infliximab. And finally, because infliximab dose escalation could not be reliably assessed with information from the national insurance database, dose escalation was not evaluated during follow-up.