Biologics show subtle differences in serious infection risk
medwireNews: The risk for serious infections in patients taking biologics for the treatment of rheumatoid arthritis (RA) differs depending on drug type, indicate data from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis.
“For the majority of patients, biologic therapies remain a safe and efficacious treatment strategy,” say Andrew Rutherford (King’s College London, UK) and fellow study authors.
“However, in a population of ‘high-risk’ individuals, differences in the relative risk of infection can have a significant impact on the absolute risk of [serious infection].”
The team found an overall incidence of serious infection, defined as one resulting in death, hospitalization, or the need for intravenous antimicrobial therapy, of 5.51 cases per 100 patient–years among 19,282 patients with RA starting a new biologic since 2001.
Etanercept was the most widely used biologic, taken by 8630 patients, and this was set as the reference drug. Among these patients, the incidence of serious infection was 5.56 per 100 patient–years.
The team found that three biologics differed significantly from etanercept in their associated risk for serious infections. Both rituximab and tocilizumab were associated with a significantly higher rate of serious infection, at a respective 6.29 and 6.98 cases per 100 patient–years.
After adjustment for age, sex, disease activity, Health Assessment Questionnaire score, disease duration, smoking, seropositivity, polypharmacy, and baseline steroid usage, only tocilizumab was still associated with a significantly higher rate of infection, with a hazard ratio (HR) of 1.21. And this was supported in sensitivity analyses in which the sample of patients was limited to those starting biologics since 2010 and those who had taken biologics before.
The lowest crude incidence of serious infection was seen among patients taking certolizumab pegol, at 3.80 cases per 100 patient–years, and the rate remained significantly lower than that of etanercept after adjustment for confounding factors (HR=0.75).
The differences in infection risk between the drugs was small, but the researchers stress that while the choice of biologic may have little impact for patients with a low baseline risk, “for patients with multiple risk factors who have a high baseline risk of infection, then choosing a drug with a slightly higher relative risk of infection can have a much larger impact on their infection risk.”
In terms of types of infections, the risk for sepsis for patients taking rituximab was about twice that for those taking etanercept, whereas rituximab was associated with half the risk for skin infections compared with etanercept. Adalimumab and certolizumab pegol were also associated with a significantly lower risk for skin infections than etanercept.
The researchers note in the Annals of the Rheumatic Diseases that while the incidence of all-cause mortality for the group of patients as a whole was low, at 0.84%, it increased significantly following a serious infection.
“Over 10% of patients who suffered a serious infection died within 30 days of the event highlighting the significance of these events,” the team writes. Sepsis, in particular, was a significant predictor of mortality and had the highest rate, at 45%. The choice of biologic did not significantly predict death from a serious infection, however.
The researchers conclude: “Recognizing the subtleties in the differential infection risk profiles between drugs is a step towards personalised medicine and safer prescribing habits.”
By Lucy Piper
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