Monitoring Biosimilars: What Switching Means for Drug-Level and ADA Testing

A biosimilar is a biologic that is highly similar to an already-approved reference product, with no clinically meaningful differences in safety, purity or potency. Over the last decade, biosimilars of the major anti-TNF antibodies, infliximab and adalimumab in particular, have moved from novelty to standard of care, driven largely by cost. For laboratories that measure these drugs, the rise of biosimilars raises a practical question: when a patient switches from the originator to a biosimilar, does the assay that tracked their drug levels and anti-drug antibodies still work?

What the switching evidence shows

The landmark NOR-SWITCH trial randomised 482 patients on stable originator infliximab to either continue or switch to the biosimilar CT-P13 and followed them for 52 weeks. Switching was not inferior to continued originator treatment on the prespecified margin, and immunogenicity rates were comparable between groups. The open-label extension that followed patients further reached the same conclusion. While the trial was not powered to prove non-inferiority within each individual disease, its breadth across indications made it a reference point for the clinical acceptability of switching, and it normalised the expectation that monitoring should continue seamlessly through a switch rather than restarting.

Assay continuity: the analytical question

From a measurement standpoint, the reassuring finding is that drug-level and ADA assays developed for an originator generally recognise its biosimilars. Because a biosimilar shares the reference product's amino-acid sequence and binding characteristics, an assay's capture and detection reagents typically bind both. Method-comparison work has shown that assays validated for originator infliximab also quantify CT-P13 biosimilars, and that anti-originator-antibody assays cross-react with biosimilar-induced antibodies, yielding consistent positive and negative calls with well-correlated titers. In practice this means a laboratory can usually maintain one assay and one set of reference ranges across a switch, preserving the longitudinal trend that makes monitoring useful in the first place.

The caveats worth keeping

"Generally" is not "always". A few points deserve attention. First, cross-reactivity should be confirmed, not assumed: before reporting biosimilar concentrations on an assay validated for the originator, a laboratory should verify performance against the specific product, ideally with spike-recovery in the relevant matrix. Second, calibrator identity matters, a kit calibrated against the originator will report biosimilar concentrations in originator-equivalent units, which is fine for trend monitoring but should be stated clearly. Third, as new biosimilars and formulations enter the market, each is a fresh analyte until shown otherwise; the safest assumption is that qualification is product-specific even when the science predicts cross-reactivity.

Why this matters for research workflows

Biosimilar adoption multiplies the number of products a laboratory may encounter while the underlying analyte, the therapeutic antibody and the immune response to it, stays conceptually the same. An assay strategy that travels across originator and biosimilar lets investigators pool and compare data rather than fragmenting it by brand. That continuity is especially valuable in pharmacokinetic and real-world studies, where the whole point is to follow exposure and immunogenicity over time and across the switches that now happen routinely in practice.

As with every assay in this series, the kits referenced are supplied for research use only and are not intended to direct patient management without appropriate independent validation. Used as research tools, cross-reactive drug-level and ADA assays make the biosimilar era far easier to study than it would otherwise be.

---

Part of AlpinaBioTech's educational series. Explore our drug-level and anti-drug-antibody ELISAs.

References

1. Jorgensen KK, Olsen IC, Goll GL, et al. 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. Lancet. 2017;389(10086):2304-2316.

2. Gecse KB, Lovasz BD, Farkas K, et al. J Crohns Colitis. 2016;10(2):133-140. doi:10.1093/ecco-jcc/jjv220. PMID:26661272. (Drug-level and ADA assays validated for originator infliximab cross-react with CT-P13 biosimilars.)

3. European Medicines Agency & European Commission. Biosimilars in the EU: Information guide for healthcare professionals. 2019 (updated edition).