While all rheumatoid arthritis (RA) patients are at higher risk than a person without RA for the painful skin rash known as shingles (also called herpes zoster), starting treatment with an anti-TNF biologic, compared to a traditional disease-modifying antirheumatic drug (DMARD), won’t likely increase that risk, according to a new study published in a recent issue of The Journal of the American Medical Association (JAMA).
“Whether a patient is starting a biologic drug or a nonbiologic DMARD, there really is no increased risk based on that drug choice,” says lead author Kevin L. Winthrop, MD, MPH, assistant professor of ophthalmology, infectious diseases and public health at Oregon Health & Science University in Portland. “I think that is reassuring, and it comes from the largest study to date in the U.S.”
Because anti-TNFs suppress the immune system, which is overactive in RA, the drugs also raise the risk of a patient developing certain infections. The concern was that the drugs would similarly raise the risk of shingles. Shingles is caused by the same virus that causes chicken pox – the varicella zoster virus. After a person has had chicken pox, the virus can lie dormant in the nerve cells for years; shingles is triggered when the immune system lets down its guard.
The possible connection between biologic drugs and shingles has been an issue of concern and previous studies have come to conflicting conclusion, including one from Germany, which found that biologics do increase risk of shingles. That increased risk was determined to be very low.
This newest study compared the rate of shingles in patients starting treatment with one of three anti-TNFs – adalimumab (Humira), etanercept (Enbrel) or infliximab (Remicade) – to those starting a traditional DMARD, including methotrexate, leflunomide, sulfasalazine or hydroxychloroquine.
Researchers analyzed data from four major U.S. databases on nearly 60,000 patients – including more than 36,000 with RA and more than 12,000 with either psoriatic arthritis, ankylosing spondylitis or psoriasis – who started treatment between 1998 and 2007.
They found 310 cases of shingles among patients taking anti-TNFs and 160 shingles cases among patients taking a traditional DMARD. But because there were almost twice as many people taking anti-TNFs as there were taking DMARDS, the rates were essentially equivalent. And even after adjusting for various factors (such as age, sex and other medical conditions), Dr. Winthrop’s team found no significant difference in shingles rates between the two groups. Nor did they find a significantly different rate between the three biologics.
However, people who took high doses of corticosteroids (10 mg or greater daily) in addition to either their medications had a significantly increased risk of shingles. That risk has been documented in other studies, Dr. Winthrop says.
The results of Dr. Winthrop’s current study dovetail with the results of a much smaller study of more than 1,600 people from the Mayo Clinic. That study found that people with RA – especially those with more severe cases – are at two-fold higher risk of getting shingles. The Mayo study also found that biologics and DMARDs do not appear to significantly raise that risk, but that corticosteroids increased risk. The study was published recently inArthritis Care & Research.
“Shingles is a serious problem for all patients, especially patients who are immune compromised,” says study author Eric L. Matteson, MD, rheumatology chair at the Mayo Clinic in Rochester, Minn. “It is advisable, if there are no contraindications, to obtain a shingles vaccination.”
The shingles vaccine is a live virus, and while it is a greatly weakened virus, there is concern that patients could develop a local or systemic infection from the vaccine. Presently, both the U.S. Food and Drug Administration and the American College of Rheumatology advise against giving the shingles vaccine to people taking biologic drugs. However, a 2012 study found that the vaccine is safe for those patients – but their findings are considered preliminary.
A new vaccine is in development, and may be safer because it is not a live vaccine, says Dr. Matteson.
Dr. Winthrop adds: “The best thing to do is to get the vaccine before starting any drug therapy, particularly biologic drugs. If you are taking prednisone, it’s in your best interest to work with your physician to either lower the dose or eliminate the drug if possible.”