No Significant Differences in Efficacy Shown Between Reference Drug, Biosimilars in Patients With IBD


Despite the insignificant differences in efficacy, biomarkers, therapeutic drug level, and ADAs, patients reported a significant number of nocebo effects.

Inflammatory bowel disease (IBD)—which includes Crohn disease (CD) and ulcerative colitis (UC)—requires long-term treatment due to it being a chronic and often debilitating condition. Although biologic therapies have changed the management of IBD and were once the central component of treatment for moderate-to-severe cases, biologic therapy is currently the main cost driver within IBD health care. A study published in Digestive and Liver Disease investigated patients with IBD following a switch from originators to biosimilars, such as infliximab (IFX) and adalimumab (ADAL) biosimilars, for the clinical efficacy, drug persistence, therapeutic drug level and immunogenicity, as well as safety and nocebo effects­.

This prospective, observational study examined patients with consecutive IBD who underwent a switch from originators to biosimilars. IFX (Remicade; Janssen Biotech) was switched to infliximab-dyyb (Inflectra; Pfizer) or ABP710 (Avsola; Remicade); and ADAL (Humira; AbbVie) was switched to adalimumab-afzb (Abrilada; Pfizer), GP2017 (Hadlima; Samsung Bioepis), adalimumab-adaz (Hyrimoz; Sandoz), or adalimumab-fkjp (Hulio; Viatris). Following the change to biosimilars, the dosing and intervals were unchanged unless a clinical need required adjustments in therapies. Further, dose optimization of biosimilars and courses of corticosteroids were allowed at the decision of the treating physicians.

A total of 210 patients aged 18 years or older (median age: 42.0; 29.0-61.0) with IBD who were treated with anti-TNF therapy were enrolled in the study. Of the patients included, approximately 81.4% had Crohn disease (CD), and the remainder had UC. Patients who underwent a mandatory non-medical switch based on reimbursement regulations, regardless of disease activity, were included in the study.

Patients were assessed for clinical disease activity, laboratory tests (eg, completed blood counts, albumin, liver function test, biomarkers, and therapeutic drug monitoring [TDM]), adverse events (AEs), and nocebo effect at week 8 prior to the switch, at baseline, and at weeks 12 and 24 following the switch. Further, data on patient demographics, disease phenotype, extent, and severity at diagnosis, as well as treatment history—including previous and concomitant medications—were collected with electronic health records at enrollment. In addition, TDM (eg, serum drug trough level and anti-drug antibodies), dosage optimization, and change of biological therapy were measured at week 8 before the switch, at baseline, and at weeks 12 and 24 following the switch to biosimilars.

Open bottle of oral adalimumab

Image credit: luchschenF |

The primary outcomes of the study were clinical efficacy, including clinical remission (CR) and corticosteroid-free clinical remission (CSF-CR) with biosimilars following a switch and sustained clinical remission. Secondary outcomes included biochemical and endoscopic remission, drug persistence, TDM, AEs, and the nocebo effect of biosimilars following the switch.

Of the 210 patients with IBD who were included in the study, approximately 56.2% were on ADAL and 43.8% were on IFX. Among those who were treated with ADAL, 53.4% had received dose intensification to 40 mg every week. There were no significant differences in the proportion of patients who remained in CR (88.1%, 91.8%, 85.8%, and 90.2%, respectively; p = 0.129) and CSF-CR (88.1%, 91.8%, 85.8%, and 90.2%, respectively; p = 0.113) at 8 weeks prior to the switch, at baseline, and at weeks 12 and 24 after the switch.

Further, the median IFX and ADAL trough levels at the switch and weeks 12 and 24 after the switch were not significantly different compared to those at 8 weeks prior to the switch. In addition, there were no significant differences in the proportion of patients maintaining the therapeutic drug level at 8 weeks before the switch (84.7%), at baseline (83.9%), and at weeks 12 (83.0%) and 24 (85.3%) after the switch. Among the patients treated with ADAL, approximately 2.5% (n = 3) developed anti-drug antibodies (ADAs). In addition, of the IFX-treated patients, approximately 2.2% (n = 2) had high-titer IFX-ADAs, and 7.6% (n = 7) had lower-titer IFX-anti-ADAs.

The overall probability of remaining on biosimilar treatment after 12 weeks of switching from the originator drug was approximately 97.1% (95% CI: 90.6%-98.2%). There was a similar probability of drug persistence between patients who underwent a biosimilar switch from an IFX- or ADAL-originator. The discontinuation rate of biosimilar therapy was approximately 4.8%, and among the 10 patients who discontinued biosimilars after the switch, 5 experienced nocebo effects, 4 no longer responded to treatment, and 1 had an acute infusion reaction. Of this small population, 3 patients switched back to the originators and 7 changed to a different biologic agent.

Key Takeaways

  1. Switch From Originators to Biosimilars in Inflammatory Bowel Disease (IBD): A prospective study investigated the differences after switching from originators to biosimilars—infliximab (IFX) and adalimumab (ADAL)—in patients with IBD. The study authors evaluated clinical efficacy, drug persistence, therapeutic drug levels, safety, and the nocebo effect following the switch.
  2. Consistent Clinical and Biochemical Activity: The study, which included 210 patients with IBD, had found no significant changes in clinical remission, corticosteroid-free clinical remission, biochemical activity, or therapeutic drug levels after the switch to biosimilars over a 24-week period. This indicates comparable efficacy between originators and biosimilars.
  3. Nocebo Effect and Drug Persistence: Despite the low biosimilar discontinuation rates (4.8%), a notable 13.3% of patients had reported nocebo effects within the first 3 months following the switch to biosimilars. The study authors note that further follow-ups and disease monitoring to address patient perceptions and ensure treatment adherence are necessary.

AEs were observed in approximately 9.5% of patients (n = 20) during the 24-week treatment duration, with infusion reactions present in 4 patients (1.9%). Further, nocebo effects were observed in approximately 13.3% of patients (n = 28) during the 24 weeks of follow-up. Of the patients who reported nocebo effects, 5 patients (2.4%) discontinued biosimilar therapy and were switched back to the originator or changed to another biological agent.

Study limitations include the relatively short follow-up period, the lack of a control group that continued to use originators, and the majority of patients being biologic-naïve which can limit their applicability to biologic-experienced IBD patients. In addition, the study authors note that they were unable to properly assess all parameters (eg, clinical, biomarkers, and TDM) at every time in all patients, due to some patients’ lack of adherence to follow-up visits and laboratory tests.

Although the findings demonstrate no significant changes in clinical or biochemical disease activity, therapeutic drug level, or immunogenicity following 24 weeks of biosimilar switching, they remain consistent with prior research. Further, a nocebo effect was frequently reported during the first 3 months after the switch. According to the researchers, follow-ups and disease monitoring is necessary to overcome nocebo effects of non-medical switching.


Wetwittayakhlang P, Karkout K, Wongcha-um A, et al. Clinical efficacy and nocebo effect following non-medical biosimilar switch in patients with inflammatory bowel disease: A prospective observational study. Digestive and Liver Disease. 2024;56(1):35-42. doi:10.1016/j.dld.2023.06.022

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