Europe’s Cheapest Way to Save Expensive Biologics Is Sitting Untested in the Lab

Some of the most expensive medicines in Europe are being dosed with a precision problem that nobody has fully priced in. Biologic drugs — the engineered antibodies that transform life with Crohn’s disease, rheumatoid arthritis, psoriasis and other chronic inflammatory diseases — can cost tens of thousands of euros per patient per year. Yet a simple blood test that measures how much of those drugs is actually circulating in a patient’s bloodstream, known as therapeutic drug monitoring or TDM, remains inconsistently used, inconsistently studied, and — according to a new position paper published in Pharmacia — inconsistently justified by the economic evidence that health systems need before they will pay for it.

The paper, authored by a European team of pharmacoeconomics researchers, takes an unusually candid look at the state of the science. Its conclusion is not that TDM fails. It is that the economic case for TDM has been built on a surprisingly narrow foundation: nearly all published cost-effectiveness analyses concern just two older TNF-α inhibitor drugs, infliximab and adalimumab, and nearly all come from wealthy countries such as the United States, the United Kingdom, the Netherlands and Spain. For the newer, even more expensive biologics now flooding into clinics — and for the low- and middle-income countries where rational drug use matters most — the economic evidence is essentially blank space.

The clinical logic behind TDM is straightforward and, on its face, compelling. Patients absorb and clear biologics at wildly different rates. Some are effectively underdosed, quietly developing antidrug antibodies that neutralize the therapy; others are overexposed, paying full price for drug concentrations that add toxicity without adding benefit. By measuring trough drug levels and antibody status, clinicians can adjust doses, extend dosing intervals, or switch strategies before a patient loses response. Done well, this should mean fewer hospitalizations, fewer steroid bursts, fewer unnecessary dose escalations, and fewer costly switches to a second-line biologic. Every avoided escalation is money that stays in the health system’s pocket.

The strongest clinical evidence comes from inflammatory bowel disease. The TAXIT trial found that proactive infliximab monitoring produced numerically higher remission rates than empiric dose management — 69 percent versus 58 percent — along with less unnecessary dose escalation, though the difference fell short of statistical significance. In pediatric Crohn’s disease, the PAILOT trial showed higher steroid-free remission with proactive adalimumab monitoring. The NOR-DRUM trial compared proactive TDM directly against standard care without monitoring and found sustained disease control over 52 weeks, a result strong enough to feed into clinical guidelines. But outside IBD, and outside TNF-α inhibitors, the picture thins out fast. Proposed therapeutic thresholds — infliximab trough levels of 5 to 10 micrograms per milliliter, adalimumab above 7 to 8 — were derived from observational studies, and their usefulness for drugs like vedolizumab and ustekinumab has never been validated in randomized trials.

That clinical uncertainty is precisely what makes the economics so messy. A cost-effectiveness analysis is only as good as its assumptions about what TDM actually does in the clinic, and the new paper documents how wildly those assumptions vary. Some studies compared proactive monitoring against reactive monitoring triggered only when a patient relapses. Others compared TDM-guided dose tapering against standard care, or test-based strategies against blind dose escalation. One model found proactive TDM dominated reactive strategies — cheaper and more effective at the same time. Another concluded the price of infliximab would have to fall before proactive monitoring could claim cost-effectiveness. Two analyses of the same Dutch INGEBIO trial reached opposite verdicts: an early model-based evaluation found TDM was not cost-effective, while a later analysis conducted alongside the trial found it dominated usual care entirely.

The health outcomes feeding these models are equally unstable. Quality-adjusted life years gained from introducing TDM have ranged from a decrease of 0.31 to an increase of 0.29 depending on the study — a spread wide enough to flip any reimbursement decision. Most analyses found little or no QALY impact at all, suggesting that if TDM pays off, it pays off mainly through drug savings and avoided healthcare utilization rather than through dramatic gains in measured quality of life. Uncontrolled studies that omit downstream costs — the price of the tests themselves, the treatments patients receive after a TDM-guided change — tend to produce implausibly rosy results, the authors warn.

Where the evidence does align, it points toward real money. One modeling study of TDM-guided dose de-escalation in Crohn’s disease projected savings exceeding €39 million across four dosing cohorts. A United States simulation of more than 160,000 infliximab-treated patients estimated that proactive monitoring would save $5,520 per member per year versus reactive TDM and $9,229 versus empiric dosing, with the savings driven mainly by reduced IBD-related hospital care. A pharmacokinetic analysis found that model-guided monitoring cut underexposure by roughly 39 percent. And a Spanish study of adalimumab tapering in rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis found that dose reduction guided by drug levels improved patients’ quality of life while cutting direct medical costs in patients with stable disease.

The paper also argues that cost-effectiveness alone cannot settle the question, because an intervention can be efficient and still unaffordable. Budget impact analysis — the unglamorous accounting exercise that estimates what a policy actually costs a payer over one to three years — is the missing half of the equation. TDM-guided tapering looks especially attractive in a world of biosimilars, where dose optimization of a cheap antibody stretches budgets further. But the authors flag a paradox: as biosimilar prices fall, the savings from dose optimization shrink, while the fixed costs of assays, laboratory turnaround and clinical interpretation grow in relative importance. The economic value of TDM is not a constant; it is a moving target that shifts with every price cut and every change in reimbursement rules.

Implementation is the other quiet barrier. Interpreting drug concentrations, especially when pharmacokinetic modeling is involved, demands expertise that many clinics simply do not have. Assay methods differ, sampling timing differs, therapeutic thresholds differ, and no harmonized European guidelines exist for how TDM should actually be done. Reimbursement criteria vary country by country, reflecting different health technology assessment frameworks and budget realities. Without standardized algorithms and clear decision rules, the authors caution, TDM risks becoming an added monitoring cost that changes nothing about treatment decisions — the worst of both worlds for a cash-strapped health system.

The prescription that emerges from the paper is concrete: pragmatic comparative trials of TDM-guided strategies against standard care, harmonized monitoring algorithms with predefined thresholds, economic evaluations that count every cost including the tests and their downstream consequences, and — urgently — studies beyond infliximab and adalimumab, in the lower-resource settings where biologics are least affordable and rational use matters most. Europe’s health systems are already spending billions on biologics. The blood test that could make every one of those euros work harder exists today. What is missing is not the technology but the evidence — and the will to generate it properly.

Subject of Research: Pharmacoeconomic evidence gaps in therapeutic drug monitoring for chronic inflammatory diseases in Europe

Article Title: Improving pharmacoeconomic evidence of therapeutic drug monitoring for chronic inflammatory diseases across Europe

Article References: Petrova, G., Tachkov, K., Brenna, E., Çakmak Barsbay, M., Holko, P., & Kawalec, P. (2026). Improving pharmacoeconomic evidence of therapeutic drug monitoring for chronic inflammatory diseases across Europe. Pharmacia, 73, Article e209129. https://doi.org/10.3897/pharmacia.73.e209129

Image Credits: AI Generated

DOI: 10.3897/pharmacia.73.e209129

Keywords: therapeutic drug monitoring, biologics, chronic inflammatory diseases, cost-effectiveness analysis, TNF-alpha inhibitors, pharmacoeconomics, budget impact analysis, biosimilars, personalized medicine, health economics, infliximab, adalimumab