We have read with great interest the article by Vande Casteele et al. Management of patients who lose response to antibodies against tumour necrosis factor (anti-TNF-α) remains largely empiric. The information provided by the determination of trough levels of the drug and antibodies could aid decision making in the case of loss of response and perhaps in preventing it in the future.[3, 4]
Enzyme-linked immunosorbent assay (ELISA) has been used in most clinical trials due to its simplicity, although its specificity may be suboptimal. Both infliximab and adalimumab and antibodies against these drugs are predominantly IgG. ELISA can detect other antibodies against human proteins, such as rheumatoid factor or antibodies against haplotypes, which may interfere in the determination of quantification of anti-TNF-α concentrations and antibody titres.[6, 7] For example, in the study by Vande Casteele et al., the Biomedical Diagnostics kit detected approximately 20% of false positive infliximab levels; this means that 2 out of 10 patients would have been erroneously considered nonresponders to anti-TNF-α instead of being correctly identified as patients with undetectable infliximab levels.
On the other hand, antibodies to anti-TNF-α drugs bind with anti-TNF-α molecules in serum to form immunocomplexes that cannot be detected using ELISA. Under these circumstances, the test may show false-negative results.[6, 7] Radioimmunoassay is more sensitive and specific than ELISA, but its main drawback is its technical complexity due to the use of radioisotopes. Other assays have been recently developed, aiming to overcome the interaction between anti-TNF-α and antibodies against the drug, but information about their clinical potential is still scarce.
In conclusion, the optimisation of anti-TNF-α therapy based on the measurement of anti-TNF-α and antibodies serum levels is promising. However, an accurate and standardised assay is not available yet. Furthermore, the usefulness of this strategy for the improvement of the outcome of patients under anti-TNF-α therapy needs to be demonstrated in prospective studies before its implementation in clinical practice.