Rheumatic Disease and Shingles: Do Treatments Boost Risk?


People who have rheumatoid or psoriatic arthritis or lupus are at increased risk for shingles. Studies suggest that treatment for the rheumatic condition may be a factor in certain circumstances.

Rondaan C, Horst G. Hempel JC, et al., Altered cellular and humoral immunity to varicella-zoster virus in patients with autoimmune diseases. Arthritis & Rheumatology (2014) Accepted manuscript. Online Sept 15, 2014. doi: 10.1002/art.38804.

Yun H, Xie F, Delzell E, et al., Risks of Herpes Zoster in Patients with Rheumatoid Arthritis According to Biologic Disease Modifying Therapy. Arthritis Care & Research (2014) Accepted manuscript. Online Sept 8, 2014. doi: 10.1002/acr.22470

Winthrop KL, YamanakaH, Valdez H, et al., Herpes Zoster and Tofacitinib Therapy in Patients With Rheumatoid Arthritis. Arthritis & Rheumatology (2014) 66:2675–2684. Online Sept 26, 2014. doi: 10.1002/art.38745

Zisman D, Bitterman H, Shalom G, et al., Psoriatic arthritis treatment and the risk of herpes zoster.Ann Rheum Dis (2014) Sep 26.  Online Sept 26, 2014. doi: 10.1136/annrheumdis-2013-205148.

Patients with inflammatory rheumatic diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) face a considerably increased risk of shingles. Treatment may boost that risk, according to some evidence from some new studies on the question.

Researchers in the Netherlands say that RA and SLE patients are at as much as a 20-fold greater risk of developing shingles compared to the general population. But they contend, based on a rather small study, that in SLE this is due largely to decreased immune responses to the shingles virus itself, not to immunosuppressant drugs. 

A large retrospective study of Medicare data similarly shows that biologic disease modifying antirheumatic drugs (DMARDs) including TNF-α blockers do not substantially influence shingles risk among older RA patients, who are already more vulnerable by virtue of age and compromised immune status.

However, the last two studies above do find that treatment increases the risk among older patients and those on steroids or certain DMARD combinations.

One of these, led by researchers at the University of Alabama- Birmingham, finds an increased risk of herpes zoster in the treatment group of RA patients in clinical trials of the Janus kinase (JAK) inhibitor tofacitinib (Xeljanz).

The other, a study including 3,121 patients in Israel’s largest health database, finds an increased risk among patients treated with corticosteroids and with combinations that include TNF inhibitors and conventional DMARDs.

The Dutch study (Rondaan et al) compared antibodies specific to Herpes zoster virus (HZV) among 38 outpatients who had SLE, 33 with granulomatosis with polyangiitis (GPA), and 51 controls unaffected by rheumatic disease. Only the SLE patients showed  increased antibodies to HZV and lower cellular immune responses against the virus.

There were no differences in antibody levels or cellular immunity to HZV between the GPA patients and healthy controls. Nor did use of biologics appear to influence shingles risk.

The study of Medicare claims for more than 29,000 RA patients treated between 2006 and 2011 compares the rates of shingles cases among those treated with etanercept (Enbrel), infliximab (Remicade), adalimumab (Humira), certolizumab, golimumab, tocilizumab (Actemra), rituximab (Rituxan), and abatacept (Orencia).

After adjustments, there were no major differences between biologics and non-biologic DMARDs. There was a greater risk for shingles among those using high-dose glucocorticoids.

The tofacitinib study (Winthrop et al) looked at data for 4,789 participants in phase II, phase III, and long-term extension trials of the JAK inhibitor. It found 239 cases of shingles associated with the drug, the most serious of them among patients treated in Asia.

The majority of those who developed shingles (87%) were women with a median age of 57. Older age and concomitant treatment with methotrexate and prednisone appeared to increase the risk.

Findings in the Israeli study (Zisman et al) are similar. Among patients with psoriatic arthritis, shingles risk was increased not only among older patients and those on steroids, but also among those taking combinations of conventional DMARDs and TNF blockers. Those treated with anti TNF-α drugs developed shingles more quickly than others. 

The related issue of vaccination against HZV arose in two of the studies, and in fact Rondaan and coauthors undertook their research to clarify the issue for patients with rheumatic disease. They conclude that HZV vaccination in SLE patients should aim to boost cellular immunity against the virus. (The American College of Rheumatology (ACR) recommends shingles vaccine for RA patients and says it’s safe in mild SLE.)

In the Medicare study, 4.1% of the RA had received shingles vaccine, a rate similar to those with other immune-mediated diseases. Not surprisingly, patients who got the HZV vaccine had a lower incidence of shingles.



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