AMSTERDAM – Patients with rheumatoid arthritis who had a high serum level of biologic immunomodulatory drugs had a statistically significant 51% higher rate of infection during their first year on the drug, compared with RA patients who maintained usual or low serum levels of the same drugs, according to an analysis of 703 U.K. patients in a national database.

The results suggest that, once patients with rheumatoid arthritis go into remission on a higher dosage of biologic agents that produce a high serum level “dose tapering may lower their risk of infection,” Meghna Jani, MD, said at the European Congress of Rheumatology.

This apparent relationship between higher biologic drug levels and increased infections “may be another reason to measure drug levels in patients; it could make their treatment safer, as well as save money,” said John D. Isaacs, MD, a professor of clinical rheumatology at Newcastle University in Newcastle upon Tyne, United Kingdom, who was a coauthor on the study.

The study used data and specimens collected in two separate, prospective U.K. studies: the British Society for Rheumatology Biologics Register-RA, which had data from more than 20,000 U.K. patients with RA who started treatment with a biologic agent, and BRAGGSS (Biologics in Rheumatoid Arthritis and Genetics and Genomics Study Syndicate), a national prospective cohort of 3,000 RA patients who had serum specimens drawn at 3, 6, and 12 months after starting biologic drug treatment and tested by an immunoassay for the concentration of the drug each patient received.

The analysis focused on 703 patients for whom there was data while they were on treatment with any of five biologic drugs: the tumor necrosis factor inhibitors adalimumab (Humira; 179 patients), certolizumab (Cimzia; 120 patients), etanercept (Enbrel; 286 patients), and infliximab (Remicade; 14 patients) and the interleukin-6 blocker tocilizumab (Actemra; 104 patients).

Dr. Jani and her associates considered serum levels that exceeded the following thresholds to categorize patients as having a high drug level: 8 mcg/mL adalimumab, 25 mcg/mL certolizumab, 4 mcg/mL etanercept, 4 mcg/mL infliximab, and 4 mcg/mL tocilizumab. The patients averaged about 59 years old, about three-quarters were women, and they had been diagnosed with RA for approximately 5-7 years. About 22% were also on treatment with a steroid, and most patients had not received prior treatment with a biologic agent.

The researchers tallied 229 diagnosed infections in the subgroup with high serum levels of their biologic drug, and 63 infections in those with levels below this threshold. After adjustment for age, sex, methotrexate use, and disease activity score, patients with high serum levels of their biologic drug had a 51% higher rate of all infections than did patients with levels that fell below the high-level threshold, reported Dr. Jani, a rheumatologist at Manchester (England) University. Analysis of the accumulation of infections over the course of 1 year of follow-up showed that this difference in infection rates became apparent after about 2 months of exposure and then began to diverge more sharply after about 5 months of exposure.

The results also showed that the rate of serious infections – defined as those needing intravenous antibiotics, hospitalization, or resulting in death – were similar in the two subgroups. The types of infections and their relative frequencies were also roughly similar in the two subgroups. Lower respiratory infections were the most common infection in both subgroups, followed by infections of the upper respiratory tract, urinary tract, and skin as the next three most common infections in both subgroups.

mzoler@mdedge.com

SOURCE: Jani M et al. EULAR 2018 Congress, Abstract OP0229.

High RA biologic drug levels linked with more infections