Switching biologic may lower risk of second infection-related hospitalization in RA



Rheumatoid arthritis patients taking an anti–tumor necrosis factor agent who had a prior hospitalization because of an infection significantly reduced their risk of a subsequent infection-related hospitalization by switching to etanercept or abatacept in a retrospective study of Medicare data.

The risk of a second hospitalization declined by 20% with abatacept (Orencia) and by 17% with etanercept (Enbrel), Huifeng Yun, Ph.D., and her colleagues reported (Ann. Rheum. Dis. 2014 March 7 [doi:10.1136/annrheumdis-2013-204011]).

"These findings provide new evidence for clinical management of high-risk RA patients and suggest that drug-specific guidance may be more appropriate when making safety-based recommendations, rather than simply lumping drugs together based on" mechanism of action, wrote Dr. Yun, an epidemiologist at the University of Birmingham, Ala., and her coauthors.

For the retrospective study, investigators examined Medicare data from 2006 to 2010 on nearly 13,000 patients with rheumatoid arthritis (RA). All of them had been hospitalized for an infection that occurred while taking a tumor necrosis factor (TNF) inhibitor and then either continued on the same medication or switched to another.

Of these, most (54.0%) were on infliximab (Remicade). Other drugs were etanercept (25.1%), adalimumab (Humira, 19.8%), certolizumab pegol (Cimzia, 0.6%), and golimumab (Simponi, 0.5%). The most common infection was pneumonia or other respiratory tract infection (30%); others included urinary tract (23%), skin/soft tissue (17%), and septicemia/bacteremia (11%).

After discharge, most started the same anti-TNF drug (79%), but 2% switched to another anti-TNF biologic, 3% switched to a non–anti-TNF biologic, and 16% didn’t get any biologic over the next 18 months. Only 10% of those who initially restarted the same anti-TNF inhibitor later switched to another biologic during follow-up.

From this primary cohort, the authors had data on 10,183 patients who received any biologic during 18 months of follow-up. During that period, 2,666 subsequent hospitalized infections occurred, with crude incidence rates ranging from of 27.1 to 34.6 per 100 person-years.

When considering the different drugs taken after hospitalization, the risk of infection was significantly lower with abatacept and etanercept, compared with infliximab (hazard ratios of 0.80 and 0.83, respectively). There were no significant associations between the types of subsequent infections and any of the drugs taken after the first infection, Dr. Yun and her colleagues said.

Another analysis seemed to indicate that the risk of a subsequent infection peaked early for etanercept, infliximab, and adalimumab and dropped off after the first 3 months. In contrast, the risk curve with abatacept and rituximab stayed fairly flat throughout follow-up, they noted.

"These findings are compatible with studies suggesting an early increased risk for anti-TNF agents that declines over time," the authors wrote. "Perhaps further accentuating these differences, the substantial majority of anti-TNF users in the analysis were restarting therapy with a medication that they had been on, whereas most abatacept and rituximab users were new users."

The findings are somewhat at odds with national recommendations, Dr. Yun and her associates pointed out. The American College of Rheumatology recommends that RA patients on anti-TNF therapy switch to a non–anti-TNF biologic after a serious adverse event, including a hospitalized infection.

"Our results suggest that the ACR recommendation may be appropriate, especially if switching to abatacept, but considering the grouped safety profile of medications defined by an anti-TNF or non–anti-TNF common [mechanism of action] may not be appropriate."

The Agency for Healthcare Research and Quality funded the study. Dr. Yun did not report any financial disclosures, but several coauthors reported numerous financial relationships with a number of pharmaceutical companies marketing drugs for RA.

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