Summaries of Must-Read Clinical Literature, Guidelines, and FDA Actions
Higher infection risk in RA seen with high blood biologic levels
Key clinical point: Dose-tapering guided by therapeutic drug monitoring has the potential for lowering infection risk and helping balance biologic safety and efficacy.
Major finding: The risk of any infection with high serum biologic drug levels was about 50% higher at 1 year when compared with low serum biologic drug levels.
Study details: The study comprised 703 patients in the British Society for Rheumatology Biologics Register – Rheumatoid Arthritis who were treated with biologic drugs and had serum samples taken as part of the Biologics in RA Genetics & Genomics Study Syndicate (BRAGGSS) cohort.
Disclosures: The BSRBR-RA is funded through the BSR, which receives restricted income from several U.K. pharmaceutical companies. These include AbbVie, Celltrion, Hospira, Pfizer, UCB, and Roche, and in the past, Swedish Orphan Biovitrum and Merck. The pharmaceutical company funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Dr. Jani has no personal conflicts of interest to disclose.
Jani M et al. Rheumatology, 2019 April;58(Suppl 3):kez105.018.
In this study, the authors use the major British Society for Rheumatology Biologics Register – Rheumatoid Arthritis and examine infections and serious infections across biologics. They define “low/normal” blood levels versus “high” blood levels based on concentration-effect curves. Examining data censored at 1 year versus incidence during 1 year, the results are somewhat inconsistent. With larger numbers available for data censored at 1 year, there is some increased risk using hazard ratios for both all infections and serious infections. With smaller numbers for incident infections during the first year, this hazard ratio does not show an effect.
These data are interesting and consistent with logic, with increasing concentration being associated with more infection, across biologics. There are a few issues, however. First, the cutpoint dividing low/normal from high appears quite arbitrary. While it is understandable that the authors combined across biologics to achieve adequate numbers of cases, the varying mechanisms of action make this approach somewhat arbitrary as well. Likewise, the issue of low numbers abrogates any significant hazard ratios when looking at incident cases, the most rigorous approach. This study supports previous data but is, unfortunately, neither significantly new data nor definitive data.
Daniel E. Furst, MD, is professor of medicine (emeritus) at the University of California, Los Angeles, an adjunct professor at the University of Washington, Seattle, and research professor at the University of Florence (Italy). He is also practices part-time in Los Angeles and Seattle.