Adalimumab Prolonged Dosing Regimen Proves Safe for RA

Extending dosing intervals of adalimumab (Humira, AbbVie) by 50% has been shown to be safe, having no clinically adverse effects on disease activity for patients with rheumatoid arthritis.

New data from a noninferiority trial, led by Merel I’Ami, MSc, of the Amsterdam Rheumatology Center in Reade, Amsterdam, in the Netherlands, found that patients using serum trough adalimumab concentrations of >8 µg/mL were able to lengthen dosing intervals from biweekly (the standard of care) to once every 3 weeks without adverse effects on control.

"Adalimumab is prescribed in a standard dose (as described by the label), without considering the huge variation in drug concentrations [among] patients," l'Ami told MD Magazine. "Drug concentration testing is a simple objective diagnostic tool. We think that rheumatologists should start the evaluation of adalimumab treatment by considering the pharmacokinetics in that individual patient. It will show the rheumatologist when drug concentrations are undetectable (occasionally, as a result of a large amount of anti-drug antibody formation), and it will show the rheumatologist when a patient is overexposed. Our study showed that patients can reduce the dose safely. Reducing this kind of overexposure will personalize treatment and save a lot of drug costs."

After screening, 55 patients were randomized 1:1 to either dose-interval prolongation of once every 3 weeks, or continuation of once every 2 weeks. The primary outcome was the change in Disease Activity Score in 28 joints (DAS28) after 28 weeks.

The trial showed that after 28 weeks, the average difference in the DAS28 was a slight improvement of -0.14± (SD 0.61) for the prolongation group (n=27), compared to the slight deterioration of the continuation group (n=24) difference of 0.30± (SD 0.52).

In the prolongation arm, 26% (n=7) of patients showed an increase of at least 0.6 in the DAS28 score, considered statistically significant by the primary endpoint, compared to 37% (n=10) of patients in the continuation group after 28 weeks (P =0.56). Two patients in the prolongation group worsened in the DAS28 score and elected to return to standard dosing, and 4 others in the group preferred the standard schedule without a worsened score.

The mean adalimumab concentration for the prolongation group decreased from 10.6 (±2.5) µg/mL to 6.6 (±2.0) µg/mL, including 7 patients having concentrations below 5 µg/mL. For the continuation arm, adalimumab concentration fell to 9.3 (±3.0) µg/mL from 10.4 (±2.4) µg/mL.

The mean difference between the two groups was 2.6 µg/mL (95% CI, 1.2-4.1 µg/mL; P = 0.001).

Two patients in the prolongation arm reported adverse events, while 14 reported an adverse event in the continuation group. No serious adverse events were reported.