Optimal adalimumab concentration in reumatoid arthritis

Researchers of Sanquin found that blood levels of Adalimumab (Humira) of 5 to 8 μg/mL had an optimal effect on rheumatoid arthritis (RA) disease activity. Patients taking concomitant methotrexate (MTX) reached significant higher blood levels of adalimumab.

Researchers from Sanquin Biologics and rheumatoid arthritis clinic Reade in amsterdam defined the therapeutic range of adalimumab in RA by determining  the concentration–effect curve. They showed that trough levels higher than 8 μg/mL had no additional effect on disease activity. This enables the most cost-effective use of this drug. This was published in the Annals of Rheumatic Diseases in March 2015.

For this prospective observational cohort study 221 consecutive RA patients were treated with 40 mg adalimumab subcutaneously every other week. The relationship between adalimumab trough levels and clinical efficacy after 28 weeks of follow-up was defined using a concentration-effect curve. The researchers determined the effect of MTX  on adalimumab trough levels by dividing patients that are and are not concomitantly using MTX.

Therapeutic range

"Adalimumab trough levels in a range of 5–8 μg/mL are sufficient to reach adequate clinical response”, said dr Gertjan Wolbink, rheumatologist, working for Sanquin and Reade. “But these levels are influenced substantially by concomitant MTX use." Patients in adalimumab monotherapy had a median adalimumab level of 4,1 μg/mL whereas patients concomitantly taking  MTX reached a median level of 7.4 μg/mL. 

Anti-drug antibodies

Wolbink suggested that functional drug levels are higher in patients taking concomitant MTX because they are less prone to develop anti-drug antibodies. These have been shown to lower functional drug levels. "Even the use of a low concomitant MTX dose aids in optimizing treatment with adalimumab”.The researchers defined the therapeutic range of adalimumab in RA by determining  the concentration–effect curve. They showed that trough levels higher than 8 μg/mL had no additional effect on disease activity. This enables the most cost-effective use of this drug.