Biosimilars in inflammatory bowel disease: Beyond evidence, toward trust and implementation

Table 1 Key evidence supporting biosimilars in inflammatory bowel disease

Ref.	Design	Population	Agent	Key finding	Clinical relevance	Contextual interpretation1
Jørgensen et al[13], 2017	RCT, double-blind, non-inferiority	482, IMDs including IBD	CT-P13 (IFX)	Non-inferior: Disease worsening 26% (originator) vs 30% (switch)	First RCT-level evidence that a single switch does not compromise outcomes	A pivotal trial, though IBD subgroup was underpowered. Provides reassurance for switching in stable patients but does not address biologic-naive initiation or multiple switches
Ye et al[14], 2019	RCT, double-blind, phase 3	220, biologic-naive CD	CT-P13 (IFX)	Comparable clinical response and remission at weeks 6 and 30	First IBD-specific RCT confirming biosimilar efficacy in naive CD	Provided IBD-specific randomized evidence that helped reduce concerns about extrapolation from non-IBD indications
Fiorino et al[16], 2017; Armuzzi et al[17], 2019	Prospective multicenter cohort	810 (initial cohort 547), IBD, Italy	CT-P13 (IFX)	Response: 73.7% naive, 78.9% switch at 24 weeks; 71% biologic-naive at 12 months	Largest prospective European biosimilar IBD cohort	Demonstrated real-world effectiveness across naive, pre-exposed, and switched patients. Response rates were broadly consistent with historical originator data, providing supportive real-world context for biosimilar use
Barberio et al[18], 2021	Propensity score-weighted	IBD cohort	ABP501, SB5 (ADA)	Comparable remission maintenance vs originator ADA	Extended biosimilar evidence beyond IFX to ADA	Methodologically valuable for using propensity-score weighting to reduce selection bias. It also extends the evidence base to adalimumab biosimilars, an increasingly relevant class in routine practice
Moura et al[19], 2026	Retrospective registry	Canadian IBD, multiple biosimilars	Multiple (IFX, ADA)	No significant difference in remission, hospitalizations, or ED visits	Real-world Canadian data supporting biosimilar initiation	Notably addresses initiation (not only switching). Observational design limits causal inference, but the breadth of outcomes measured strengthens clinical applicability
Komaki et al[15], 2017	Systematic review and meta-analysis	IBD, CT-P13 studies	CT-P13 (IFX)	Equivalent efficacy and safety across pooled studies	Systematic synthesis of early biosimilar IBD data	Did not identify a clear signal of inferiority across heterogeneous studies. Useful for clinicians seeking a summary-level evidence assessment, though limited by the quality of included studies
Kritzinger et al[23], 2025	Retrospective observational cohort	81, IBD (85.2% CD), Canada (McGill)	Ustekinumab biosimilar (non-medical switch from originator)	Complete response stable: 87%, 85.9%, 84.3%, 92.7% (week 8 before switch, baseline, week 12, week 24, not significant). Drug sustainability 96.3% at 12 weeks, 95% at 24 weeks. Discontinuation 4.9%	First real-world ustekinumab biosimilar switching data in IBD	Extends biosimilar evidence beyond anti-TNF therapy to the IL-12/23 pathway. The high short-term persistence observed despite substantial prior biologic exposure supports the feasibility of ustekinumab biosimilar switching, although longer-term data remain needed

¹The “contextual interpretation” column reflects the authors’ assessment and does not represent formal guideline recommendations.

RCT: Randomized controlled trial; IMDs: Immune-mediated diseases; IBD: Inflammatory bowel disease; CD: Crohn’s disease; IFX: Infliximab; ADA: Adalimumab; ED: Emergency department; TNF: Tumor necrosis factor; IL: Interleukin.

Table 2 Clinical scenarios and suggested approaches for biosimilar use in inflammatory bowel disease

Clinical scenario1	Risk profile	Suggested approach	Monitoring	Key considerations
Biologic-naive initiation	Generally low	Biosimilar as default first-line biologic on pharmacoeconomic grounds	Standard protocol (CRP, FCP at 4-6 weeks, 12-week, 6-month)	Lowest nocebo risk (no prior reference point). Cost savings most impactful at population level. Shared decision-making still recommended
Stable remission on originator	Low to moderate	Non-medical switch with structured communication (positive framing, one voice)	Standard protocol + clinical reassessment at 4-6 weeks	Highest nocebo risk. Communication quality is the key determinant of success. One voice strategy essential. Most extensively studied scenario (NOR-SWITCH, PROSIT-BIO)
Prior switching history	Moderate	Individualized assessment; consider TDM at baseline and 12 weeks	Enhanced: TDM + biomarkers at closer intervals	Prior immunogenicity signals may warrant proactive TDM. Distinguish prior pharmacological failure from nocebo-driven discontinuation before deciding approach
Complex disease (fistulizing CD, extensive colitis, EIM)	High	Caution advised; biosimilar initiation feasible but switching should be deferred during active disease	Enhanced: TDM + endoscopy/imaging as indicated	Treatment stability takes precedence over cost optimization. If switching, ensure that disease is in remission with objective confirmation before transition
Special populations (pregnancy, pediatric, postoperative)	High (context-dependent)	Defer switching; maintain current effective therapy. Biosimilar initiation in naive patients may be considered case-by-case	Standard + disease-specific monitoring	Limited data on switching during pregnancy or postoperative period. Stability and continuity of care are priorities. Pediatric data emerging but still limited

¹This table represents a pragmatic author-proposed framework and does not constitute formal guideline recommendations. Clinical judgment should be exercised for individual patients.

CD: Crohn’s disease; EIM: Extraintestinal manifestations; TDM: Therapeutic drug monitoring; CRP: C-reactive protein; FCP: Fecal calprotectin.

Table 3 Comparison of biosimilar adoption challenges: High-income vs resource-limited settings

Factor	High-income setting	Resource-limited setting1
TDM availability	Routine and proactive; integrated into standard switching protocols	Limited or unavailable in most centers; reliance on clinical assessment alone[58]
Consultation time	15-30 minutes; dedicated IBD clinics with multidisciplinary teams	5-10 minutes; general GI outpatient setting without dedicated IBD infrastructure[37]
Patient education resources	Nurse-led programs, digital tools, IBD helplines, patient associations	Limited; no dedicated IBD nurse specialist role in most settings[59]
Fecal calprotectin access	Standard of care; point-of-care testing increasingly available	Often unavailable or unaffordable; not routinely reimbursed[58]
Physician biosimilar training	Integrated into CME; supported by peer networks and professional societies	Variable; limited formal exposure; knowledge gaps regarding extrapolation and interchangeability[63]
Reimbursement structure	Established biosimilar incentive programs; gainsharing models	Restricted formularies; predominantly out-of-pocket payment; biosimilar-specific incentives rare[61]
Switching policy framework	Structured programs with shared decision-making; institutional protocols	Often policy-driven without concomitant communication support or monitoring infrastructure[12]
Nocebo risk environment	Moderate; mitigated by dedicated stewardship programs and infrastructure	High; structural amplification due to convergence of short consultations, low health literacy, social media misinformation, and low baseline trust[12,37]

¹Reference numbers correspond to the manuscript reference list. This comparison is intended to highlight structural differences that may influence biosimilar adoption outcomes; it does not imply that resource-limited settings are uniformly disadvantaged across all domains.

TDM: Therapeutic drug monitoring; CME: Continuing medical education; GI: Gastroenterology; IBD: Inflammatory bowel disease.