During the first year after starting a new therapy, patients with autoimmune diseases appear to experience a similar rate of serious infections irrespective of whether the new drug is a biologic or a nonbiologic agent.
Infections requiring hospitalizations were nearly identical, regardless of the initial therapy, in a large retrospective cohort study of patients with rheumatoid arthritis (RA), inflammatory bowel disease (IBD), or psoriasis and spondyloarthropathies.
But within the group of rheumatoid arthritis patients taking biologics, infliximab was associated with significantly more infections than was etanercept or adalimumab (adjusted hazard ratio 1.25). "This observation may have important implications for the interpretation of studies that report on tumor necrosis factor [TNF]–alpha [antagonists as a group, perhaps because the prevalence of infliximab use could have influenced observed associations," wrote Dr. Carlos G. Grijalva of Vanderbilt University, Nashville.
The drug regimens studied included the use of infliximab-based regimens, many of which used methotrexate to inhibit anti-infliximab antibodies. "Disentangling the effect of individual drugs when used concurrently is difficult. Nevertheless, we noted that concurrent methotrexate use was similar for the other TNF-alpha antagonists."
Also, in a strong dose-dependent fashion, glucocorticoid use at baseline significantly increased the infection risk for patients with rheumatoid arthritis or psoriasis and spondyloarthropathy, Dr. Grijalva and his colleagues wrote in a study posted online in JAMA on Nov. 6 (2011 Nov. 6 [doi:10.1001/jama.2011.1692]).
Dr. Grijalva and his coinvestigators based their findings on data extracted from four large U.S. databases – three included Medicaid and Medicare participants and one included pharmaceutical assistance programs for the elderly and disabled – as part of the Safety Assessment of Biologic Therapy (SABER) project.
Outcomes were assessed within the first 365 days of initial therapy with the TNF-alpha antagonists infliximab, adalimumab, or etanercept and with nonbiologic therapies specific to each disorder.
For rheumatoid arthritis, the comparator therapies were leflunomide, sulfasalazine, and hydroxychloroquine after any use of methotrexate in the previous year. For inflammatory bowel disease, the comparators were azathioprine and mercaptopurine. For psoriasis and the spondyloarthropathies, the comparators were methotrexate, hydroxychloroquine, sulfasalazine, and leflunomide.
The cohort consisted of 10,484 matched pairs of rheumatoid arthritis patients, 2,323 with inflammatory bowel disease, and 3,215 with psoriasis or a spondyloarthropathy. Overall, 20% of patients were aged 65 years or older. Over the 1-year follow-up period, 225 patients died; of these, 148 had rheumatoid arthritis, 38 had inflammatory bowel disease, and 39 had psoriasis.
There were 1,172 serious infections requiring hospitalization, and 53% were for pneumonia or skin and soft tissue infections. The death rate was 3.6% for RA patients, 2% for IBD patients, and 7% for those with psoriasis and the spondyloarthropathies.
Among those with RA, the infection rate was 8.16 per 100 person-years for those taking a biologic agent and 7.78 per 100 person-years for those on a nonbiologic agent, a nonsignificant difference.
However, the authors said, there was a significant difference in infections when considering glucocorticoid use. Those who used up to 5 mg/day were 32% more likely to be hospitalized; 5-10 mg/day, 78% more likely; and more than 10 mg/day, three times more likely to have a hospitalization, compared with patients not taking a glucocorticoid.
When the investigators broke the biologics down into individual infection associations, infliximab was associated with a significant increase, compared with the nonbiologics (adjusted HR 1.26). Infliximab was also associated with significantly more hospitalizations than either etanercept or adalimumab (adjusted HR 1.26 and 1.23, respectively).
Among those with IBD, the rate of infection did not differ significantly between those taking nonbiologic and biologic drugs (9.6 per 100 person-years and 10.9 per 100 person-years, respectively). Nor was there a significant association of infection with baseline glucocorticoid use.
Among those with psoriasis or a spondylarthropy, the infection rates were 5.37 per 100 person-years for nonbiologics and 5.4 per 100 person-years for biologics – not significantly different. But again, baseline glucocorticoid use significantly affected these rates. Those taking 5-10 mg/day of glucocorticoids were twice as likely to be hospitalized as those not taking the drug. Those taking more than 10 mg/day were 2.7 times more likely to have a hospitalization.
Compared with prior studies, this analysis found higher rates of infection overall, a finding that might be due to the large numbers of low-income, elderly, and disabled patients – particularly vulnerable groups.
The researchers said the findings are limited by reliance on coded information from claims and limited information on actual use of medications. The study was primarily sponsored by the Food and Drug Administration and the Department of Health and Human Services. Dr. Grijalva did not have any financial disclosures, but eight of the study investigators reported multiple associations with pharmaceutical companies.