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— Mark

Clinical Pain Medicine, May 16 2016

Patients with rheumatoid arthritis (RA) face an increased risk for serious infection and hospitalization. Use of opioid analgesics raises that risk, according to a study published in Arthritis & Rheumatology (2016;68:323-331).

“The highest rates of infections were associated with the current use of long-acting opioids, high doses of opioids and opioids with potentially immunosuppressive properties,” said first author Andrew Wiese, MPH, a doctoral student in epidemiology at Vanderbilt University Institute for Medicine and Public Health, in Nashville, Tenn.

“This paper argues that opioid analgesics may carry additional risks that were previously unrecognized by both physicians and patients; i.e., the risk for infectious complications in a vulnerable population such as in patients with rheumatoid arthritis,” said Petros Efthimiou, MD. Dr. Efthimiou, who was not involved in the study, is associate chief of rheumatology at New York Methodist Hospital and associate professor of medicine and rheumatology at Weill Cornell Medical College, both in New York City.

“The findings from this study provide further support for the observed association between opioid use and immunosuppression,” he said.

The study was a case series analysis of a retrospective cohort of 13,796 community-based adults with RA, who were enrolled in Tennessee Medicaid during 1995 to 2009, and served as their own controls. “Compared to nonopioid use, we observed the highest increases in the rates of infection during periods of current long-acting opioid use—a twofold increased risk potentially immunosuppressive opioids, and at the highest dosages, both around a 70% increased risk,” said Mr. Wiese.

Overall, periods of opioid use were associated with a nearly 40% increase in the risk for infection compared with periods of nonopioid use (incidence rate ratio, 1.39; 95% CI, 1.19-1.62), Mr. Wiese noted.

In treating rheumatic disease, opioids are used relatively rarely, said Dr. Efthimiou, explaining that disease-modifying antirheumatic drugs (DMARDs) are the medication of choice for reducing inflammation and pain. But when opioids are considered, “the newly described infectious risk will need to be explained to the patient, and be part of the informed consent prior to prescribing.”

The investigators also considered the possibility that pain could explain the observed association between opioid use and infections, said Dr. Wiese. To that end, the investigators examined patients’ rate of serious infections while taking nonsteroidal anti-inflammatory drugs, and found no association.

“The impetus for the study was the concern that the immunosuppressive effects of certain opioids could be especially problematic for populations that are susceptible to infections,” said Dr. Wiese. “Patients with rheumatoid arthritis, who have chronic pain and who may frequently receive opioids, are [already] at high risk of infections due to their underlying disease and from other medications used for disease control,” he pointed out.

Previous in vitro human studies and animal models had shown that certain opioids such as morphine, methadone, and fentanyl have immunosuppressive actions. The mechanisms include inhibition of T cell receptor signaling, depletion of lymphocytes and reductions in natural killer cell activity, according to the current report.

“Since we do not believe that all opioids have the same potential for immunosuppression, additional studies are needed to examine specific opioids and formulations that are particularly problematic,” said Dr. Wiese. “That additional information could then inform the selection of appropriate pain control medications in susceptible populations.”

—David C. Holzman


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