Introduction
Current data suggests that biosimilar is safe and effective for patients with inflammatory bowel disease (IBD).1-2 However, the drug discontinuation and nocebo effect after switching from originator to biosimilar have increased over time. 3
Aims & Methods
We aimed to evaluate clinical efficacy, biomarkers activity, therapeutic drug monitoring (TDM) adverse events (AEs), and nocebo effect in IBD patients who underwent biosimilar switch. A prospective observational study of consecutive IBD patients who underwent non-medical biosimilar switch at McGill University Health Centre, Montreal, Canada, between April 1, 2022 – March 31, 2023. The patients were follow-up until 24 weeks following the switch. Disease activity, biomarkers, TDM and AEs including nocebo effect were captured at 8 weeks before switch, at time of the switch (baseline), 12 and 24 weeks after the switch.
Results
A total of 210 patients were included [81.4% were Crohn’s disease (CD), median age at inclusion: 42 years (IQR 29-61)]. There was no significant difference in the rates of clinical remission at week 8 before the switch, baseline, week 12, and 24 after the switch; 89.0%, 93.4%, 86.3% and 90.8%, p=0.129. The rates of sustained clinical remission at week 12 and week 24 after switching were 79.4% and 69.6% respectively. The proportion of patients remaining in biomarkers remission was not significantly different at week 8 before the switch, baseline, week 12, and 24 after the switch; CRP: 81.3%/ 74.7%/ 81.2%/ 73.0%, p=0.343; Fecal calprotectin: 78.3%/ 74.5%/ 71.7%/ 76.3%, p=0.829. The rates of maintaining in therapeutic level (84.7%/ 83.9%/ 83.0%/ 85.3%, p=0.597) and prevalence of positive anti-drug antibodies remained unchanged before and after the switch. Nocebo effect was observed in 13.3% and 4.3% of patients discontinued biosimilar therapy. Main results of the study outcomes in IBD patients following Biosimilar switch is shown in Table 1.
| Outcomes monitoring, n (%) | 8 weeks before the switch | At switch
(baseline) | Week 12 after switch | Week 24 after switch | p-value |
| Clinical remission | 187/210 (89.0%) | 184/197 (93.4%) | 164/190 (86.3%) | 167/184 (90.8%) | 0.129 |
| Steroid-free clinical remission | 185/210 (88.1%) | 181/197 (91.8%) | 163/190 (85.8%) | 166/184 (90.2%) | 0.113 |
| IBD flare | NA | 6/184 (3.3%) | 14/167 (8.4%) | 10/161 (6.2%) | 0.121 |
| CRP remission | 113/139 (81.3%) | 59/79 (74.7%) | 69/85 (81.2%) | 73/100 (73.0%) | 0.343 |
| Fecal calprotectin remission | 65/83 (78.3%) | 41/55 (74.5%) | 43/60 (71.7%) | 58/76 (76.3%) | 0.829 |
| Maintaining in therapeutic level | 72/85 (84.7%) | 47/56 (83.9%) | 88/106 (83.0%) | 99/116 (85.3%) | 0.597 |
| Adalimumab anti-drug Ab positive | 0/44 (0%) | 0/28 (0%) | 2/49 (4.1%) | 2/50 (4.0%) | 0.345 |
| Infliximab anti-drug Ab positive | 1/41 (2.4%) | 0/28 (0%) | 1/57 (1.8%) | 2/66 (3.0%) | 0.616 |
| Nocebo effect | NA | 9 (4.3%)
| 13 (6.4%)
| 6 (3.0%)
| NS |
Conclusion
Despite a significant number of early nocebo complaints within the first 6 months after the biosimilar switch, no significant changes were found in clinical efficacy, biomarkers, therapeutic drug level, and anti-drug antibodies.
References
1. Danese, S. et al. ECCOJC 2017, 11, 26–34
2. Jørgensen, K.K. et al.The Lancet 2017, 389, 2304–2316
3. Queiroz et al. Arq. Gastroenterol. 2020, 57, 232–243