The Theranostic Revolution
The word "theranostics" — combining therapy and diagnostics — captures one of the most important shifts in modern medicine: the recognition that we cannot treat patients optimally without simultaneously measuring the biological response to that treatment.
For decades, this was easy to ignore. Aspirin, beta-blockers, statins, antibiotics — these drugs work, broadly speaking, at standard doses across most of the population. Pharmacokinetics matters, but not so dramatically that routine measurement was clinically essential.
Biological drugs changed everything.
The Variability Problem
Monoclonal antibodies — adalimumab, infliximab, rituximab, vedolizumab and the dozens of others now in clinical use — display an extraordinary degree of inter-patient pharmacokinetic variability. Two patients on the same dose of the same drug, treated for the same indication, can have 10-fold or greater differences in serum drug concentrations.
This variability has multiple sources:
- Body composition — drug distribution differs significantly with weight, fat mass, and lean tissue
- Disease activity — inflamed tissue acts as a drug sink, reducing serum levels
- Albumin levels — affecting Fc-receptor recycling of IgG-class biologics
- Immunogenicity — patient-specific anti-drug antibodies (ADAs) accelerate clearance
- Concomitant medications — methotrexate, for example, suppresses immunogenicity
The clinical consequence is that fixed dosing produces wildly different drug exposure across patients. Some are over-treated and exposed to unnecessary risk. Many more are under-treated — receiving a drug that has effectively been silenced by anti-drug antibodies, while paying the full clinical and economic cost of treatment.
Why Trough Levels?
Trough levels — drug concentrations measured immediately before the next dose — are the gold standard for therapeutic drug monitoring of biological agents. They represent the minimum sustained drug exposure the patient experiences during a dosing cycle.
Decades of clinical research have established that:
- Sub-therapeutic troughs predict treatment failure — for many biologics, troughs below threshold values correlate with loss of clinical response
- Adequate troughs predict durable response — patients in the therapeutic window typically maintain remission
- Supratherapeutic troughs flag opportunities for de-escalation — saving substantial cost while maintaining clinical efficacy
"The economic implications are profound: a hospital pharmacy budget can save tens of thousands of euros per patient per year through informed monitoring — while simultaneously improving outcomes."
The ADA Dimension
Trough levels alone tell only half the story. When a patient develops anti-drug antibodies, the drug is rapidly cleared from circulation — manifesting as low or undetectable troughs.
But not all immunogenicity is the same. Free anti-drug antibodies (ADAs) are immediately detectable; however, when drug is present in serum, ADAs may be sequestered in immune complexes — invisible to standard assays unless the complexes are first dissociated. Total ADA assays reveal these hidden antibodies.
And finally — most importantly clinically — not all ADAs are functionally relevant. Many anti-drug antibodies bind without affecting drug function. Neutralising antibodies (NAbs) are the subset that block the drug's pharmacological action — and these are the ones that truly predict treatment failure.
The Theranostic Toolkit
A complete theranostic platform for biotherapy monitoring requires four complementary measurements:
- Drug levels (TDM) — quantitative measurement of free drug at trough
- Free ADAs — immediately accessible anti-drug antibodies
- Total ADAs — including those in drug-ADA immune complexes
- Neutralising ADAs — functionally significant antibodies via T-CAP NAb-style assays
This is precisely what the SHIKARI® platform delivers — and it is no accident that we describe our work as theranostic. Every kit is a bridge between diagnosis and therapy. Every measurement informs a treatment decision.
The Clinical Reality in 2026
Despite a decade of evidence, therapeutic drug monitoring of biological drugs remains underused in many healthcare systems. The reasons are complex — assay availability, reimbursement, clinical workflow, prescriber familiarity. But the trajectory is unmistakable: as biological drugs continue to dominate pharmaceutical pipelines, and as healthcare systems increasingly demand value-based outcomes, quantitative biotherapy monitoring will become the standard of care.
Matrix Biotek supports research into that transition from its European commercial and R&D&I headquarters in Barcelona, working with ISO 13485 manufacturing in Ankara. All SHIKARI® products presented by Matrix Biotek are For Research Use Only and are not intended to serve as the sole basis for diagnosis or treatment decisions.
Looking Forward
The next frontier is integration: combining drug-level monitoring with biomarkers of disease activity, inflammation, and immune dysregulation — building a truly personalised picture of each patient's response. Our active R&D&I pipeline, including the LEITAT collaboration on Human S100A12 and the Long-COVID Screening Pathway, points toward this integrated theranostic future.
We are proud to lead this work from Barcelona — a city that has become, in the past decade, one of Europe's most exciting biomedical research ecosystems. From Talent Garden Barcelona, the next generation of theranostic tools is being developed.
References available on request. SHIKARI® and CoronaHunter® are registered trademarks of Matriks Biyoteknoloji Ltd. Şti., licensed for use by Matrix Biotek S.L. All Matrix Biotek SL products are For Research Use Only (RUO) and are not intended for use in diagnostic procedures.