"This research highlights the importance of risk management during the first year of treatment with TNF inhibitors in rheumatoid arthritis patients," Dr Masayoshi Harigai from Tokyo Medical and Dental University, Tokyo, Japan, told Reuters Health in an email. "It is just like takeoff of an airplane: physicians (i.e., pilots) have to be careful as much as possible at the beginning of treatment with the biologics."
Working with patients enrolled in the Rheumatoid Arthritis Patients for Long-Term Safety (REAL) study, Dr Harigai and colleagues assessed the risk for serious infections associated with three years of continuous use of infliximab or etanercept, or other TNF blockers in patients who switched.
Serious risk of infection elevated
There were 727 RA patients on infliximab (335) or etanercept (392) and 571 RA controls not exposed to TNF antagonists at the beginning of the study, according to a report online March 15 in Arthritis Care & Research.
Overall, compared with patients unexposed to TNF antagonists, patients exposed to TNF antagonists were 67% more likely to experience a serious adverse event and 2.04 times more likely to develop a serious infection during the three-year study.
Patients treated with infliximab were 49% more likely to have a serious adverse event but not significantly more likely to develop a serious infection, compared to patients treated with etanercept.
When they looked more closely, the researchers found that the risk of serious infection was significantly elevated (2.4-fold) in the TNF antagonist group during the first year of treatment, but not in years two and three combined.
RA treatment is a lifelong journey
Other factors significantly associated with an increased risk of serious infection included increasing age, chronic pulmonary comorbidity, higher mean disease activity score including 28-joint counts (DAS28), mean dosage of methotrexate above 8 mg/week, and mean oral prednisolone dose of 10 mg/day or higher.
"Because treatment for RA continues for many years or is life-long in the majority of patients, the examination of long-term drug retention rates using a prospective cohort study is important for evaluation of biologics," Dr Harigai said. "In our recently published work in Annals of the Rheumatic Diseases (accepted but not yet in PubMed), we analysed drug retention rates, reasons for discontinuation, and relevant risk factors for drug discontinuation due to adverse events."
Several of the authors report extensive relationships with a number of pharmaceutical companies, and the study was supported by grants from Abbott Laboratories, Bristol-Myers Japan, Eisai Co. Lit., Chugai Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corp., Takeda Pharmaceutical Co. Ltd., and Pfizer Japan Inc.
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