Rheumatoid arthritis patients' response to treatment with infliximab may be improved by adjusting the dosage according to serum trough levels of infliximab, as well as to pretreatment levels of C-reactive protein, a study has indicated.
An open, prospective observational study of 105 consecutive patients with rheumatoid arthritis “confirms the relationship” between trough serum concentrations of infliximab and the extent of clinical improvement in patients taking the drug, reported G.J. Wolbink, M.D., of the Jan van Breemen Institute in Amsterdam, and associates.
The study also showed that levels of pretreatment C-reactive protein (CRP) correlate negatively with serum trough levels of infliximab and clinical response, they said.
“As infliximab is expensive, it might be efficient to adjust the infliximab dosing schedule after measurement of the serum infliximab concentration,” the investigators said.
In addition, “patients with high pretreatment CRP levels might benefit from higher dosages of infliximab than patients with low CRP levels,” they said (Ann. Rheum. Dis. 2005;64:704–7).
The investigators measured serum trough infliximab levels before intravenous infusions of 3 mg/kg infliximab, a TNF blocking treatment, at 0, 2, 6, and 14 weeks.
They assessed disease activity before each infusion using the 28-joint count Disease Activity Score (DAS28). In addition, they used European League Against Rheumatism response criteria to classify patients at 14 weeks as “responders” or “nonresponders,” and they categorized patients into three groups according to their infliximab levels.
(Nonresponse was defined as a DAS28 decrease after 14 weeks of 0.6 or less, or a decrease between 0.6 and 1.2 with an attained DAS of greater than 5.1).
At 14 weeks, nonresponders had significantly lower median serum trough infliximab concentrations than responders (0.5 vs. 3.6 mg/L). The association remained significant after correction for potential confounders such as baseline CPR, baseline DAS28 score, and rheumatoid factor.
Moreover, patients categorized as having low infliximab levels at 14 weeks less often fulfilled the EULAR response criteria than patients with intermediate and high infliximab levels (50% vs. 90% and 88%). They also had significantly less improvement in the DAS28 score (−0.9 vs. −2.0 and −2.4).
Pretreatment levels of CRP—used as an indirect marker for TNF production—correlated negatively with infliximab levels at each dosage interval.
And during the last treatment interval (6–14 weeks) the change in the DAS28 score of patients with low pretreatment CRP levels differed significantly from that of patients with high pretreatment CRP levels (−0.2 vs. 0.6), the investigators reported.
The majority of patients were women (82%) with a mean disease duration of 12 years and a mean DAS28 score at entry of 6.1. Most had used methotrexate, and this as well as other stable drug treatments were continued during the study.
