Neue Studien

Antibodies against TNF blockers correlate
with clinical responses in RA

Radstake TRDJ et al. Formation of antibodies against infliximab and adalimumab strongly correlates with functional drug levels and clinical responses in rheumatoid arthritis. Ann Rheum Dis published online 19.11.2008 (doi: 10.1136/ard.2008.092833).

Background: TNF-alpha blockers are increasingly used to treat rheumatoid arthritis. Although many patients show very good responses to these medications, a considerable percentage of patients do not adequately respond to this treatment. The current study focussed on potential correlations of clinical responses, soluble drug levels of TNF blockers and antibody formation in RA patients receiving infliximab and adalimumab.

Methods: consecutive enrolment of 69 patients fulfilling the 1987 ACR criteria starting new treatment with infliximab or adalimumab. All patients had a DAS28 >3.2. Infliximab was given intravenously at 3 mg/kg at baseline and after 2, 6 and 14 weeks; adalimumab was given at 40 mg biweekly s.c. concomitant medications were kept at a constant dosage during the study. All sera were tested for infliximab/adalimumab levels and anti-infliximab/anti-adalimumab antibodies.

Results: 35 patients received infliximab, 34 adalimumab. Clinical responses as estimated by the EULAR criteria, correlated significantly with the levels of serum infliximab/adalimumab and the formation of anti-infliximab/anti-adalimumab antibodies (the higher the level of drugs in serum and the lower the level of anti-infliximab and anti-adalimumab antibodies, the better the response). Non-respondership was significantly associated with undetectable or very low serum levels of the drug. In contrast good responders had no detectable levels of anti-TNF blocker antibodies in the vast majority of patients.

Conclusion: The authors conclude that the clinical response to the two TNF blockers infliximab and adalimumab closely follows the drug levels and the presence of antibodies directed against the drugs.

Discussion: It is well known that TNF blockers are very successful in the treatment of RA, however, a considerable percentage of patients do not respond or not adequately respond to these agents. Furthermore the response may decline over time on one TNF blocker. These facts may well correlate with the presence of antibodies to the drugs and the effective levels of drug concentrations in serum. This study represents a solid body of arguments for these correlations.
This brings us to some questions: Should we measure the drug levels in serum in order to predict response in single RA patients for the future? Does the addition of immunosuppressants (prednisone, methotrexate and others) decrease or limit the amount of antibodies to TNF blockers and by this increase response rates? Such questions are not clear at all, considering the fact that in this study, the use of prednisolone was higher in non-responders compared to responders; the dosages of methotrexate varied from 10 to 30 mg once per week in those receiving methotrexate, and the mean dosage of methotrexate was 20 mg for all response groups (good response, moderate and no response). Further studies are needed to help us in decisions on how to use concomitant medications.

Beat A. Michel, Zürich

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