Real-World Study: Nonmedical Switch to Infliximab Biosimilar Is Safe, Effective in Pediatric Patients With IBD

A real-world study of children and young adults with inflammatory bowel disease (IBD) switched from the infliximab reference product to a biosimilar concluded effectiveness of anti-tumor necrosis factor (TNF)-α treatment was maintained over 12 months based on stable remission rates and biochemical markers.

No serious adverse events were observed, and no patients developed antidrug antibodies. The patients received a total 379 biosimilar infusions at an estimated savings of $11,260 based on average sales price and $556,223 based on the wholesale acquisition cost.

According to the authors, “a lack of pediatric data exists surrounding clinical outcomes when switching from an originator to a biosimilar.” Safety, effectiveness and cost savings are established for switching to biosimilars in adults, they noted.

Infliximab is a first‐line treatment for pediatric patients with IBD but the cost of biologics, such as infliximab, are “a key driver of drug spending in the United States,” the authors said, citing reports that biologics account for up to 65% of health care costs for patients with IBD.

Since many payers are mandating nonmedical switching to biosimilars, the investigators assessed clinical outcomes 1 year before and 1 year after a nonmedical switch from the infliximab originator to a biosimilar in children and young adults with a retrospective review of patient records. Cost savings were also estimated.

The researchers analyzed records for 53 patients between the ages of 4 and 22 (mean, 18) years undergoing an insurance-driven nonmedical switch from the infliximab reference product (Remicade) to a biosimilar. Most patients switched to infliximab-dyyb (Inflectra), and 1 patient each switched to infliximab-abda (Renflexis) and infliximab-axxq (Avsola).

Physician global assessment (PGA) scores were similar 1 year before and after switching. Of the 47 patients with PGA scores recorded, 44 (94%) were quiescent before and after switching, 2 (4%) were quiescent before and mild after switching, and 1 (2%) was mild before and quiescent after switching.

There were no significant differences in biochemical markers albumin, C-reactive protein, hemoglobin, or erythrocyte sedimentation rate before and after switching. Infliximab trough levels remained similar after switching. No patients developed antidrug antibodies or experienced infusion reactions or serious adverse events. Two patients experienced psoriasis-like rashes, which the authors commented is thought to be “an anti-TNF class-wide effect and not exclusive to biosimilar use.” Seven patients underwent dose escalation due to low infliximab levels, while four underwent de-escalation.

Five patients had discontinued biosimilar treatment 6 months after the switch: 3 switched back to the reference product because of perceived lack of efficacy, 1 patient switched to adalimumab, and 1 changed drugs due to psoriasis-like rash.

At 12 months, 4 patients had transferred to another medical center; 2 more patients switched from infliximab to adalimumab, and 2 more switched back to the originator because of perceived lack of efficacy.

Five of the 53 patients reported worsening symptoms after switching to infliximab‐dyyb and switched back to the reference product, and their symptoms resolved. However, the worsening in clinical symptoms occurred in all 5 patients in the absence of any changes in biochemical markers. These patients may have experienced the nocebo effect, the authors said, noting they continued throughout the study to improve patient education to minimize misconceptions and reduce the nocebo effect. Four of the 5 patients who switched back to the reference product were switched earlier on in the study “and may have received less effective education and reassurance.”

Throughout the study period, 379 infusions of infliximab biosimilars were administered, including 2420 vials of infliximab‐dyyb, 45 vials of infliximab‐abda, and 48 vials of infliximab-axxq. Cost savings were estimated at $11,260 based on average sales price (ASP) and $566,223 based on WAC for all patients combined. Regarding the large difference between the 2 estimates, the authors said that WAC is the most commonly paid price, although some institutions may have contracted discounts, and therefore, it may overestimate cost savings. In contrast, ASP is used to set Medicare reimbursement, and since this study was made up mostly of commercially insured patients, it might underestimate cost savings.

The authors concluded that clinical remission rates, inflammatory markers, and infliximab levels remained similar with no serious adverse events of anti-drug antibodies after a one‐time nonmedical switch to an infliximab biosimilar in children and young adults. Plus, switching led to significant cost savings. To the authors’ knowledge, theirs is the first pediatric study in the US evaluating safety and effectiveness of a nonmedical switch and the largest worldwide, and their findings are consistent with pediatric studies completed in other countries. They added that future studies are needed to evaluate the safety of nonmedical switching in patients with active disease and on multiple switches in pediatric populations.

Reference

McNicol M, Abdel-Rasoul M, McClinchie MG, Morris GA, Boyle B, Dotson JL, Michel HK, Maltz RM. Clinical outcomes and cost savings of a nonmedical switch to a biosimilar in children/young adults with inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2024;78(3):644-652. doi:10.1002/jpn3.12153