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Biologics, JAK inhibitors increase risk for shingles, other infectious diseases
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BOSTON — Several biologic therapies used by rheumatologists, including rituximab, tocilizumab, abatacept and others, can increase the risk for infectious disease in patients, according to findings presented here.
During a presentation at the 2018 Interdisciplinary Autoimmune Summit, Kevin Winthrop, MD, MPH, a professor of public health and associate professor of infectious diseases and ophthalmology at the Oregon Health and Science University, noted that rheumatologists should also be aware of the infection risks associated with prednisone, as well as their patient’s comorbidities.
“When you look at the body of literature, I think the signal that emerges is that infliximab does have a higher risk estimate for serious infection [than other biologics],” Winthrop said. “I can also tell you that the biggest driver of infection risk is prednisone use and your patients’ comorbidities. Those two factors drive risk more than the drugs you are going to use, so just keep that in mind.”
According to Winthrop, previously reported incidence rates of serious infections among patients treated with biologics by 6- month intervals include:
- Adalimumab (Humira, AbbVie): 3.9 to 5.1 events per 100 patient years;
- Rituximab (Rituxan; Genentech, Biogen): 3.9 to 4.3 events per 100 patient years;
- Tocilizumab (Actemra, Genentech): 3.8 to 5.1 events per 100 patients years;
- Golimumab (Simponi Aria, Janssen Biotech): 5.09 events per 100 patients years;
- Etanercept (Enbrel, Amgen): 3.8 events per 100 patient years; and
- Abatacept (Orencia, Bristol-Myers Squibb): 2 to 3.1 events per 100 patient years.
Winthrop also singled out the particular issue of herpes zoster, or shingles, in rheumatology, due to its elevated risk associated with many of the biologic agents prescribed by rheumatologists. According to Winthrop, Medicare data indicates that shingles incidence rates per 1,000 years for patients with lupus, rheumatoid arthritis, inflammatory bowel disease, psoriatic arthritis and ankylosing spondylitis all carry a 1.5- to 3-fold greater risk for the disease.
He added that some of this increased risk is due to the specific rheumatologic conditions themselves. However, some of the risk is attributable to prednisone and some biologics, but particularly tofacitinib and other JAK inhibitors.
According to Winthrop, tofacitinib carries a uniquely high risk for herpes zoster compared to biologic agents, with a hazard ratio that is approximately double that of rituximab, tocilizumab, abatacept and others.
“In terms of reducing risk, in a study we did of patients using JAK inhibitors, prednisone and methotrexate, after modeling all the data, we found that prednisone was clearly the big factor in driving the JAK inhibitor risk,” Winthrop said. “There was some of the risk driven by methotrexate, but it was not really statistically significant.” – by Jason Laday
Reference:
Winthrop K. Predicting and Preventing Serious Infections with Biologic Therapies. Presented at: IAS 2018; April 27-29, 2018; Boston.
Disclosure: Winthrop reports consulting fees from AbbVie, BMS, Eli Lilly, Galapagos, Pfizer, Regeneron and UCB.