Patients taking opioids for rheumatoid arthritis are at significantly higher risk of serious infection, particularly those taking long-acting formulations or opioids known to have immunosuppressive properties, new data suggest.
While it has been known for some time that opioids have wide-ranging adverse effects, this is the first convincing evidence of an increased risk of infection associated with opioid use in patients with rheumatoid arthritis, Dr. Samuel Whittle, consultant rheumatologist at the Queen Elizabeth Hospital in Adelaide, Australia, said when asked to comment on the study.
Dr. Whittle, who was not involved in the study, said that these data add to the growing body of evidence that the adverse effects of opioids outweigh the benefits.
“It fits with our general sense these days that opioids really are a poor choice of analgesics in people with rheumatoid arthritis, but people continue to prescribe them because our analgesic armory is not that good,” he said.
Andrew D. Wiese of Vanderbilt University, Nashville, Tenn., and his colleagues analyzed a retrospective cohort of 1,790 patients with rheumatoid arthritis who were enrolled in Tennessee Medicaid during 1995-2009 and experienced at least one hospitalization for serious infection. The patients served as their own controls during periods of opioid nonuse. The rate of infection in these patients was 39% higher when they were taking opioids, compared with periods of nonuse, after adjusting for age, season, nursing home residency, and medication use.
The rate of infection was twice as high when they were using long-acting opioids, compared with nonuse, and 72% higher for the use of immunosuppressive opioids. New opioid use also more than doubled the risk of serious infection in the study (Arthritis Rheumatol. 2015 Oct 16. doi: 10.1002/art.39462)
Researchers also found evidence of a dose-response effect, as patients taking 60 mg or more of morphine equivalent per day had a 73% greater rate of infection than in periods of nonuse, compared with a 24% higher rate in those taking less than 15 mg morphine equivalent per day.
Patients who experienced infections were most likely to get a nonpneumonia infection, while the rates of pneumonia infection were not significantly different between periods of opioid use and nonuse.
To assess whether pain could have been a confounding factor, the researchers looked at nonsteroidal anti-inflammatory medication use as the exposure of interest and found no significant increase in the rate of hospitalizations for serious infections when compared with nonuse.
“The potential association between the risk of infection and opioid use is supported by the literature regarding the immunosuppressive effects of certain opioids from in vitro experiments and animal models, including morphine, methadone, and fentanyl (fentanyl [was] not included in our study, which is restricted to oral formulations),” the investigators wrote.
“Although our study lends support to the idea that opioids might cause further immunosuppression in patients with RA, these patients are already at higher risk of infection and possibly more likely to receive opioid therapy compared to other patient populations. Further studies are needed to determine whether this association exists in other patient populations.”
Another big research challenge, Dr. Whittle said, is “to learn better the mechanisms for persistent pain in people with rheumatoid arthritis, and hopefully through that we might be able to target therapies a little bit better.”
The study was supported by the National Institute on Aging and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. There were no conflicts of interest declared.