Switching from originator infliximab to biosimilar CT-P13 compared with maintained treatment with originator infliximab (NOR-SWITCH): a 52-week, randomised, double-blind, non-inferiority trial

Jørgensen KK, et al.

Lancet 2017 · PMID 28502609 (PubMed, opens in a new tab) · doi 10.1016/S0140-6736(17)30068-5 (full paper, opens in a new tab)

Figure 1. Disease worsening over 52 weeks, originator minus CT-P13. The square is the adjusted difference and the line its 95% CI. CT-P13 was non-inferior because the whole interval lies to the right of the dashed 15-point margin.

Data for this figure: Difference, percentage points (95% CI). Left of the null line: Favours originator. Right: Favours CT-P13. Non-inferiority margin −15 points.
Outcome	Originator	CT-P13	Estimate (confidence interval)	P
Disease worsening, Primary endpoint · adjusted, per protocol (primary)	53/202 (26%)	61/206 (30%)	−4.4 (95% CI −12.7 to 3.9)

The trial was not powered for non-inferiority within Crohn's disease or UC, so the conclusion rests on the pooled result.

Source: Jørgensen 2017, abstract (per-protocol set; all six diseases). The non-inferiority margin of 15% was prespecified.

Structured abstract

BackgroundBiosimilar infliximab cost much less, but clinicians and patients worried that switching stable patients from the originator might cause loss of disease control or more immunogenicity.

MethodsPhase 4, randomised, double-blind, non-inferiority trial (40 Norwegian centres); 52 weeks; government funded. 482 patients. Primary endpoint: Disease worsening during 52 weeks (non-inferiority margin 15%).

ResultsPrimary result. Disease worsening 26% (53/202) with originator vs 30% (61/206) with CT-P13 (per-protocol); adjusted difference −4.4% (95% CI −12.7 to 3.9). Non-inferiority shown.

Take-homeSwitching stable patients from originator infliximab to biosimilar CT-P13 is not inferior to staying on the originator; this underpins provincial biosimilar switching policies.

Table 1. Trial at a glance

Patients	482
Population	Adults on stable originator infliximab for at least 6 months. Full analysis set: Crohn's disease 155 (32%), ulcerative colitis 93 (19%), spondyloarthritis 91 (19%), rheumatoid arthritis 77 (16%), psoriatic arthritis 30 (6%), plaque psoriasis 35 (7%).
Comparison	Switch to biosimilar CT-P13 vs continue originator infliximab, same dosing regimen
Drugs	infliximab, infliximab biosimilar (CT-P13)
Classes	Anti-TNF, Biosimilar
Published	Jørgensen KK, et al. Lancet 2017;389:2304–16.

Key points

Adverse events were similar: serious 10% vs 9%, overall 70% vs 68%, leading to discontinuation 4% vs 3% (originator vs CT-P13).
The trial was not powered to show non-inferiority within individual diseases.
Open extension to week 78 (380 patients, all on CT-P13): disease worsening 16.8% in those on CT-P13 throughout vs 11.6% in those switched at week 52; adjusted risk difference 5.9% (95% CI −1.1 to 12.9) (PMID 30762274).
Exploratory Crohn's and UC analyses of the main and extension trials found no differences in activity scores, CRP, calprotectin, drug levels, antidrug antibodies or adverse events (PMID 32965617).
British Columbia (first Canadian province to mandate a non-medical switch, 2019): at 12 months, infliximab continuation 94.9% after switching vs 90.1% on originator; P=0.18 (264 vs 99 patients; retrospective) (PMID 39139221).

Limitations

Mixed immune-mediated diseases; IBD subgroups were not powered for non-inferiority.
A single switch to a single biosimilar; multiple switches were not tested.
Disease worsening was a composite of disease-specific measures.

Commentary

NOR-SWITCH is the randomised, double-blind evidence that a single switch from originator infliximab to a biosimilar is safe and effective. It is the trial most often cited by Canadian provinces that require patients to switch to biosimilars.

British Columbia introduced the first mandatory non-medical switch in North America in 2019, and other provinces have followed. Population data from British Columbia show that most patients stayed on biosimilars after the switch; by the end of 2022, 13.5% had moved from a biosimilar back to an originator or to another class (PMID 42157439).

In practice: explain the switch, keep the same dose and interval, and look for objective inflammation (calprotectin, CRP, a trough level) before attributing new symptoms to the biosimilar.

Journal club

PopulationAdults on stable originator infliximab for at least 6 months. Full analysis set: Crohn's disease 155 (32%), ulcerative colitis 93 (19%), spondyloarthritis 91 (19%), rheumatoid arthritis 77 (16%), psoriatic arthritis 30 (6%), plaque psoriasis 35 (7%).

InterventionSwitch to biosimilar CT-P13

ComparisonContinue originator infliximab, same dosing regimen

Primary outcomeDisease worsening during 52 weeks (non-inferiority margin 15%).

Design

Phase 4, randomised, double-blind, non-inferiority trial (40 Norwegian centres); 52 weeks; government funded. 482 patients.

Primary result. Disease worsening 26% (53/202) with originator vs 30% (61/206) with CT-P13 (per-protocol); adjusted difference −4.4% (95% CI −12.7 to 3.9). Non-inferiority shown.

Validity and applicability

Mixed immune-mediated diseases; IBD subgroups were not powered for non-inferiority.
A single switch to a single biosimilar; multiple switches were not tested.
Disease worsening was a composite of disease-specific measures.

Where it sits now

Switching stable patients from originator infliximab to biosimilar CT-P13 is not inferior to staying on the originator; this underpins provincial biosimilar switching policies.

Questions for discussion

The margin was 15 percentage points. Is that an acceptable loss of efficacy for a switch made to save money?
Non-inferiority was judged in the per-protocol set. Why is a per-protocol analysis often preferred in non-inferiority trials, and what would the full-analysis result add?
IBD subgroups were not powered. What evidence would you want before switching a patient with Crohn's disease a second time, to another biosimilar?

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