RESEARCH - Rates and risk factors for shingles in patients with RA

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RATES AND RISK FACTORS FOR HERPES ZOSTER IN PATIENTS WITH

RHEUMATOID ARTHRITIS

EULAR 2004

F. Wolfe, K. Michaud: Wichita, United States

The prevalence and incidence of Herpes zoster infection in RA is

unknown. The purpose of this study was to investigate whether H. zoster

infection rates are increased in RA, and whether RA specific therapies

(particularly TNF inhibitors) increase the risk of H. zoster infection

in persons with RA.

Methods: Participants enrolled in the National Data Bank for

Rheumatic Diseases were queried in mailed questionnaires at 6 month

intervals over a five year period. Incident H. zoster infection was

determined by patient self-report as ever infection (based on first

report at any time within enrollment in the Data Bank) or infection

within the last 6 months (identified by specific query, as above).

Predictive models using lagged variables in 6-month intervals were

constructed using regression, linear regression, and generalized

estimating equations (GEE) regression.

Results: 17,827 RA patients were included (mean age 61 years,

median disease duration 12 years) compared to 3112 OA patients (mean age

63 years). The lifetime prevalence of H. zoster infection among RA

patients was 15.2 per 100 compared with 16.9 per 100 in OA patients.

However, after adjusting for age, an important confounding variable in

H. zoster infection, the lifetime prevalence of H. zoster infection

among RA patients was 15.0 per 100 compared to 14.4 per 100 in OA

patients. The overall annual incidence rate of H. zoster infection in RA

patients was 2.8 cases per 100 patient years and increased with

increasing age, with an annual incidence rate of 1.7 cases per 100

patient years for ages 20-30 years compared to 3.1 cases per 100 patient

years for ages 60-70 years.

Univariate predictors of H. zoster infection in the following 6

months among RA patients:

IRR

comorbidity 1.1

HAQ 1.2

Cyclophosphamide use 7.4

Azathioprine use 1.7

Any prednisone dose 1.3

In univariate analysis, no significant association between

methotrexate, etanercept, or infliximab and increased risk of H. roster

infection was found.

Multivariate predictors of H. zoster infection in the following 6

months among RA patients:

IRR

Cyclophosphamide use 5.8

Prednisone 5.1-10 mg/day 1.4

Prednisone >10 mg/day 1.5

In multivariate analysis (adjusted for age, sex, and disease

activity), no significant association between methotrexate, etanercept,

infliximab, prednisone 0-5 mg/day, or azathioprine use was found.

When RA patients were stratified into mutually exclusive groups

based on treatment (no DMARD or biologic, DMARD only, biologic only, and

DMARD + biologic), the groups with use of biologics only and DMARD +

biologic demonstrated significantly higher incidence rates of H. zoster

infection (HR 1.3 (95% CI 1.0 - 1.7) and 1.5 (95% CI 1.1 - 2.0)

respectively) compared to the group without DMARD or biologic use in

multivariate modeling. This relationship was not significant when these

groups were compared to the group treated with DMARDS alone.

Conclusions: H. zoster infection is slightly more common in RA

than age matched OA controls. Neither TNF inhibitor nor methotrexate

therapy appears to independently increase the risk of H. zoster

infection. However, combination therapies of TNF inhibitors and DMARDS

may pose an elevated risk. Patients treated with cyclophosphamide,

azathioprine, or prednisone at doses greater than 5mg per day are at a

greater risk for developing H. zoster infection.

Editorial Comments: These data elegantly fill gaps in knowledge

about clinical aspects of RA. The lack of finding an increased zoster

risk with the use of biologics or methotrexate is particularly useful

when counseling patients about potential side-effects of these

medications, although the potential increased risk associated with

combination regimens still leaves some questions for further study in

this area. Relevant clinical questions which cannot be answered by this

study are whether persons with RA, by virtue of medications received as

therapy or by RA disease itself, are at a greater risk of more severe

outbreaks of zoster or longer disease duration when they occur.

http://www.hopkins-arthritis.som.jhmi.edu/edu/eular2004/ra-epidemiology-zoster.h\

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