Real-World Study Produces Positive Data on CT-P13 in North American Patients With IBD

A real-world study on Pfizer and Celltrion Healthcare’s infliximab biosimilar (infliximab-dyyb, Inflectra; CT-P13) demonstrated positive clinical and patient-reported outcomes in patients with inflammatory bowel disease (IBD) in the United States and Canada.

In the study, published in Advances in Therapy, the authors said biologics such as infliximab have “changed the therapeutic landscape” for IBD, the collective term for Crohn disease (CD) and ulcerative colitis (UC), relapsing and remitting inflammatory diseases of the gastrointestinal system. However, “cost remains a concern.” The reference infliximab (Remicade), a monoclonal antibody to tumor necrosis factor alpha (TNF), was approved by the US FDA in 1998 and European Medicines Agency (EMA) in 1999. Infliximab-dyyb was the first infliximab biosimilar approved in the European Union and United States in 2013 and 2016.

The biosimilar was approved based on extrapolation from clinical studies on rheumatoid arthritis (RA), and only “limited” real-world data has been published on treatment of IBD with CT-P13 in North America, according to the authors.

A total of 115 patients (mean age 44 years) across 24 sites in United States and Canada were followed for 12 months after enrolling and initiating treatment with infliximab-dyyb, 67 with CD and 48 with UC. Of 115 patients, 84 completed the 12-month study. Some patients were biologic-naive (n = 39), whereas others were switching from the reference product to the biosimilar (n = 57) or from other biologics (n = 19). Most patients switching from the reference product (80.4%) were switching due to cost, reimbursement, or insurance coverage.

Clinical outcomes were measured by partial Mayo (pMAYO) score for UC and Harvey Bradshaw Index (HBI) for CD. Patient-reported outcomes included quality of life, psychological, and work productivity measures. Health care resource utilization and adverse events (AEs) were also reported.

Remission rate increased in UC, remained stable in CD

Overall, 65 of 115 patients (57.0%) were in remission at baseline, and 64 of 84patients (81.0%) were in remission at 12 months. In patients with UC, 35.4% were in remission at baseline, and 87.1% at 12 months. In CD patients, the remission rate was 72.7% at baseline, and 77.1% at 12 months.

Among biologic-naïve patients with UC, the remission rate increased significantly from 5.6% at baseline to 90.9% at 12 months, and the average pMAYO decreased significantly from 5.67 to 1.09. Remission rate and HBI scores did not significantly change from baseline to 12 months in biologic-naive patients with CD.

In patients switching from the reference product, overall and in UC and CD, remission rates were not significantly different at baseline and 12 months (75.4% and 83.0% overall). However, in patients with UC switching from the reference product, pMAYO significantly decreased from 1.38 to 0.29.

Among patients with CD, 30.8% of those who were biologic-naïve and 6.7% of those who switched from the reference product had a clinical response to treatment. The authors noted that since 65% of biologic-naive patients with CD were in remission at baseline, this “limited their room for clinical response.”

Improvements in “nearly all” patient-reported outcomes among biologic-naïve patients

The authors said that “nearly all” patient-reported outcomes significantly improved from baseline to 12 months in biologic-naive patients, including indicators of health-related quality of life, work productivity, treatment satisfaction, and psychological outcomes.

In patients switching from the reference product, patient ratings on these outcomes were not significantly different from baseline to 12 months, except for an improvement in work absenteeism and work impairment score. Patient-reported impairment in daily activities due to IBD and patient-perceived treatment effectiveness improved significantly in overall and in biologic-naïve patients.

Data suggests health care resource utilization decreased over time

During the baseline period, 9.6% of patients reported an IBD-related hospitalization and 10.4% of patients reported an emergency department visit compared to 1.2% and 3.6% of patients during the 12-month observation period. The mean number of non-infusion gastroenterologist visits was similar during the baseline period and at 12 months. The investigators said these findings “suggest that hospitalization, ED visits, and outpatient visits decreased over time, which could be due to improvements observed in patients’ clinical outcomes and [patient-reported outcomes].”

No new safety signals

The authors said they observed no new safety signals during the study. There were 59 AEs in 40 patients, 29 (49.2%) of which were mild, 23 (39.0%) were moderate, and 7 (11.9%) were severe. Of the 59 events, 22 were classified as related to the study treatment, 1 of which—a hypersensitivity reaction—was severe. The most common AEs related to treatment included gastrointestinal disorders, infusion-related reactions, bleeding disorders, and hypersensitivity reactions. “AEs occurred at rates consistent with the known AE profile for infliximab,” the authors wrote.

Six patients discontinued treatment due to an AE; these were development of anti-drug antibodies, community-acquired pneumonia, hypersensitivity reaction, liver abscess, drug-induced lupus, and psoriasiform dermatitis and joint pain.

First evaluation of treatment satisfaction in patients switching from the reference product

The authors believe their study is the first to prospectively evaluate treatment satisfaction during a switch from the reference product to infliximab-dyyb in patients with IBD, claiming their findings “suggest that these patients remained satisfied with infliximab-dyyb in terms of its effectiveness, side effects, and convenience.”

The investigators acknowledged limitations of their study. Since they did not collect data on therapeutic drug monitoring, correlations between drug concentration and outcomes could not be reported. Additionally, their study included a smaller than expected sample size, due to difficulty with patient enrollment because of lack of formulary availability or insurance coverage of CT-P13, and some patients lost to follow-up. However, they noted, almost 70% completed all 4 study visits.

The investigators concluded that clinical outcomes improved in biologic-naïve patients with UC and were maintained in patients with CD. Patient-reported outcomes improved in biologic-naïve patients, and were maintained in patients switching from the reference product. They noted that post-approval comparative studies such as theirs “can play a key role in building a real-world evidence base to help inform clinical practices and policy decisions.”

Reference

Abraham B, Eksteen B, Nedd K, et al. Impact of infliximab-dyyb (infliximab biosimilar) on clinical and patient-reported outcomes: 1-year follow-up results from an observational real-world study among patients with inflammatory bowel disease in the US and Canada (the ONWARD study). Adv Ther. 2022;39:2109–2127. doi:10.1007/s12325-022-02104-6