Rheumatoid Arthritis: Target Adalimumab Level Determined

Janis C. Kelly

December 19, 2013

Adalimumab (Humira, AbbVie Inc) blood levels of 5 to 8 μg/mL had the greatest effect on rheumatoid arthritis (RA) disease activity, Dutch researchers report in an article published online December 10 in the Annals of the Rheumatic Diseases. Patients taking concomitant methotrexate (MTX) reached the recommended blood levels at lower doses of adalimumab.

Adalimumab trough levels greater than 8 μg/mL had no additional beneficial effect on disease activity, according to Gertjan Wolbink, MD, from the Jan van Breemen Research Institute/Reade and the Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Academic Medical Centre, Amsterdam, The Netherlands.

The researchers' goal was to determine the concentration–effect curve of adalimumab in RA to identify a therapeutic range and facilitate the most cost-effective use of this drug, which US researchers have estimated costs $16,978 per patient with RA per year.

The prospective observational cohort study examined clinical efficacy and weekly adalimumab trough levels in 221 consecutive patients treated with 40 mg adalimumab subcutaneously every other week for 28 weeks. Patients were stratified according to whether or not they were taking MTX. Disease activity was measured using the disease activity score in 28 joints, and patients were categorized as good responders, nonresponders, or moderate responders using European League Against Rheumatism response criteria.

"Adalimumab trough levels in a range of 5–8 μg/mL are sufficient to reach adequate clinical response. These levels are influenced substantially by concomitant MTX use," the authors write.

Mean adalimumab levels at 28 weeks of follow-up were 4.1 μg/mL in patients receiving adalimumab monotherapy and 7.4 μg/mL in patients who were also receiving MTX (P < .001).

The researchers suggested that MTX might contribute to increasing adalimumab blood levels by reducing inflammation and lowering the number of targets for adalimumab to bind to. "Therefore, we can conclude that even the use of a low concomitant MTX dose aids in optimising treatment with adalimumab, at least during the first 6 months of treatment, since patients taking MTX might need a lower dose of adalimumab to obtain an effective concentration with maximal clinical benefits," the authors write.

Dr. Wolbink told Medscape Medical News that laboratory tests for measuring adalimumab blood levels are readily available for clinical use. "I would recommend testing the adalimumab blood level at least once at 6 months or when therapy is not effective enough," he said. "The results of our study answer one important question [What is the therapeutic range for adalimumab in RA?] and raise the question of why we do not test the level routinely."

Eric L. Matteson, MD, MPH, told Medscape Medical News that applying the proposed monitoring will require that tests be inexpensive and that there be a change in how adalimumab is marketed.

"If the monitoring is cheap, it could be something to consider if it makes it possible to reduce the dose of the drug. The drug would have to be available in flexible dosing aliquots, which currently it is not. From a practical point of view, since the levels are summary data, we don't know which patients will be the ones who will be able to get by on these levels, and which won't, so drug prescription decisions will still be driven by doctor and patient assessments of clinical response," said Dr. Matteson, who is chair of the Division of Rheumatology at the Mayo Clinic, Rochester, Minnesota, and who was not involved in this study.

Tests for adalimumab levels are currently available from Sanquin Diagnostic Services in the Netherlands and from Prometheus Laboratories, San Diego, California, which markets the Anser ADA test for monitoring of adalimumab drug levels and antiadalimumab antibody levels in patients with inflammatory bowel disease, at a cost of $250.00.

The study was funded by an unrestricted grant of Wyeth Pharmaceuticals. One coauthor has received consultancy fees from Abbott, Roche, Pfizer, MSD, UCB, BMS, and Wyeth and payment for lectures from Abbott, Roche, and Pfizer. One coauthor has received honoraria for lectures from Pfizer and AbbVie. One coauthor has received honoraria for lectures from Abbott, Roche, and Pfizer. One coauthor has received honoraria for lectures from Pfizer, AbbVie, and UCB. Dr. Wolbink has received a research grant from Wyeth Pharmaceuticals and honoraria for lectures from Amgen, UCB, BMS, AbbVie, and Pfizer. Dr. Matteson has disclosed no relevant financial relationships.

Ann Rheum Dis. Published online December 10, 2013. Abstract

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