Incidence of herpes zoster in Japanese patients with rheumatoid arthritis from 2005 to 2010

Abstract

Objective. To clarify the incidence and the risks of herpes zoster infection in Japanese patients with rheumatoid arthritis (RA).

Methods. By using a self-report of occurrence of herpes zoster in patients with RA in a large observational cohort study from 2005 to 2010, the standardized incidence rate was calculated. A Cox model was used to analyze risk factors for occurrence of herpes zoster.

Results. A total of 7,986 patients (female 83.1%) accumulated 30,140 patient-years of observation, and 366 events were confirmed. The standardized incidence rate per 1,000 patient-years was 9.1 (95% confidence interval (CI) 6.2–12.9) in total, 7.8 (3.6–14.8) in men, and 10.3 (6.8–15.0) in women. The risk factors for herpes zoster were age [/10 years: Hazard ratio (HR) 1.268, 95% CI 1.153–1.393, p < 0.0001), high disease activity compared with remission (HR 1.642, 95% CI 1.067–2.528, p < 0.05), prednisolone (< 5 mg/day compared with 0 mg/day: HR 1.531, 95% CI 1.211–1.936, p < 0.001; ≥ 5 mg/day compared with 0 mg/day: HR 1.471, 95% CI 1.034–2.093, p < 0.05), and methotrexate (HR 1.382, 95% CI 1.076–1.774, p < 0.05).

Conclusion. This study quantified the historical incidence and risk for herpes zoster in Japanese RA patients, and is a benchmark for future studies.     

Rates and predictors of hydroxychloroquine retinal toxicity in patients with rheumatoid arthritis and systemic lupus erythematosus

Objective

Hydroxychloroquine (HCQ) retinopathy is of concern because of the potential seriousness of visual loss and the medicolegal consequences of failure to detect toxicity. However, there have been limited demographic data on which to base recommendations for screening. We have studied the largest unselected series of patients to date to evaluate the risk of toxicity and the relevance of purported risk factors.

Methods

We studied 3,995 patients with rheumatoid arthritis or systemic lupus erythematosus who had used HCQ, including 1,538 current users. We screened for self‐reported toxicity, and followed up on positive cases with detailed interviews and specialist confirmation. We categorized cases as “definite or probable” if there was bull's eye maculopathy or visual field loss.

Results

Of the lifetime users of HCQ, 6.5% discontinued therapy because of an eye problem, including 1.8% who reported HCQ retinal problems. However, definite or probable toxicity was documented in only 0.65% (95% confidence interval 0.31–0.93). The risk of toxicity was low in the initial 7 years of exposure, and was approximately 5 times greater after 7 years of usage (or 1,000 gm total exposure). Toxicity was unrelated to age, weight, or daily dosage. Eye examinations were obtained annually by 50.5% and every 6 months by 40.4% of patients.

Conclusion

HCQ toxicity remains uncommon, but increases markedly with the duration of therapy and exceeds 1% after 5–7 years. Toxicity was unassociated with age, daily dosage, or weight. These findings will aid the reformulation of screening guidelines.     

The risk of herpes zoster in patients with rheumatoid arthritis in the United States and the United Kingdom

OBJECTIVE: To determine whether the incidence of herpes zoster is elevated in patients with rheumatoid arthritis (RA) and whether herpes zoster is associated with use of disease-modifying antirheumatic drugs (DMARDs) in patients with RA. METHODS: Two retrospective cohort studies were conducted using data from a US integrated managed care database (PharMetrics claims database) from 1998-2002 and the UK General Practice Research Database (GPRD) between 1990-2001. Rates of herpes zoster among patients with RA and randomly sampled non-RA patients were compared. A nested case-control analysis was performed within each RA cohort to examine the effect of current treatment on herpes zoster risk. RESULTS: A total of 122,272 patients with RA from the PharMetrics database and 38,621 from the GPRD were included. The adjusted hazard ratios of herpes zoster for patients with RA compared with non-RA patients were 1.91 (95% confidence interval [95% CI] 1.80-2.03) in the PharMetrics database and 1.65 (95% CI 1.57-1.75) in the GPRD. In the PharMetrics database, current use of biologic DMARDs alone was associated with herpes zoster (odds ratio [OR] 1.54, 95% CI 1.04-2.29), as was current use of traditional DMARDs alone (OR 1.37, 95% CI 1.18-1.59). In the GPRD, current use of traditional DMARDs was associated with herpes zoster (OR 1.27, 95% CI 1.10-1.48). In both data sources, use of oral corticosteroids was associated with herpes zoster regardless of concomitant therapies. CONCLUSION: Data from 2 large databases suggested that patients with RA are at increased risk of herpes zoster. Among patients with RA, DMARDs and/or use of oral corticosteroids appeared to be associated with herpes zoster.     

Safety of JAK inhibitor use in patients with rheumatoid arthritis who developed herpes zoster after receiving JAK inhibitors

Clinical Rheumatology - To determine the safety of Janus kinase inhibitor (JAKi) use following herpes zoster (HZ) reactivation in patients with rheumatoid arthritis (RA). Medical records of all...     

Cutaneous abnormalities in rheumatoid arthritis compared with non-inflammatory rheumatic conditions

BACKGROUND: Cutaneous abnormalities are common in rheumatoid arthritis, but exact prevalence estimates are yet to be established. Some abnormalities may be independent and coincidental, whereas others may relate to rheumatoid arthritis or its treatment. OBJECTIVES: To determine the exact nature and point prevalence of cutaneous abnormalities in patients with rheumatoid arthritis compared with those in patients with non-inflammatory rheumatic disease. METHODS: 349 consecutive outpatients for rheumatology (205 with rheumatoid arthritis and 144 with non-inflammatory rheumatic conditions) were examined for skin and nail signs by a dermatologist. Histories of rheumatology, dermatology, drugs and allergy were noted in detail. RESULTS: Skin abnormalities were reported by more patients with rheumatoid arthritis (61%) than non-inflammatory controls (47%). More patients with rheumatoid arthritis (39%) than controls (10%) attributed their skin abnormality to drugs. Cutaneous abnormalities observed by the dermatologist were also more common in patients with rheumatoid arthritis (76%) than in the group with non-inflammatory disease (60%). Specifically, bruising, athlete's foot, scars, rheumatoid nodules and vasculitic lesions were more common in patients with rheumatoid arthritis than in controls. The presence of bruising was predicted only by current steroid use. The presence of any other specific cutaneous abnormalities was not predicted by any of the variables assessed. In the whole group, current steroid use and having rheumatoid arthritis were the only important predictors of having any cutaneous abnormality. CONCLUSIONS: Self-reported and observed cutaneous abnormalities are more common in patients with rheumatoid arthritis than in controls with non-inflammatory disease. These include cutaneous abnormalities related to side effects of drugs or to rheumatoid arthritis itself and other abnormalities previously believed to be independent but which may be of clinical importance.     

The predictors of foot ulceration in patients with rheumatoid arthritis

This study was conducted to determine the predictors of foot ulceration occurring in patients with rheumatoid arthritis (RA) without diabetes. A multi-centre case control study was undertaken; participants were recruited from eight sites (UK). Cases were adults diagnosed with RA (without diabetes) and the presence of a validated foot ulcer, defined as a full thickness skin defect occurring in isolation on / below the midline of the malleoli and requiring > 14 days to heal. Controls met the same criteria but were ulcer naive. Clinical examination included loss of sensation (10g monofilament); ankle-brachial pressure index (ABPI); forefoot deformity (Platto); plantar pressures (PressureStat); RA disease activity (36 swollen/tender joint counts) and the presence of vasculitis. History taking included past ulceration/foot surgery; current medication and smoking status. Participants completed the Health Assessment Questionnaire (HAQ) and Foot Impact Scale. A total of 83 cases with 112 current ulcers and 190 ulcer naïve controls participated. Cases were significantly older (mean age 71 years; 95 % confidence interval [CI], 69–73 vs. 62 years, 60–64) and had longer RA disease duration (mean 22 years; 19–25 vs. 15, 13–17). Univariate analysis showed that risk of ulceration increases with loss of sensation; abnormality of ABPI and foot deformity. Plantar pressures and joint counts were not significant predictors. HAQ score and history of foot surgery were strongly associated with ulceration (odds ratio [OR]?=?1.704, 95 % CI 1.274–2.280 and OR?=?2.256, 95 % CI 1.294–3.932). Three cases and two controls presented with suspected cutaneous vasculitis. In logistic regression modelling, ABPI (OR?=?0.04; 95 % CI, 0.01–0.28) forefoot deformity (OR?=?1.14; 95 % CI, 1.08–1.21) and loss of sensation (OR?=?1.22; 95 % CI, 1.10–1.36) predicted risk of ulceration. In patients with RA, ABPI, forefoot deformity and loss of sensation predict risk of ulceration but, in contrast with diabetes, raised plantar pressures do not predict risk.     

Direct medical costs and their predictors in patients with rheumatoid arthritis

Objective

To estimate total direct medical costs in persons with rheumatoid arthritis (RA) and to characterize predictors of these costs.

Methods

Patients (n = 7,527) participating in a longitudinal study of outcome in RA completed 25,050 semiannual questionnaires from January 1999 through December 2001. From these we determined direct medical care costs converted to 2001 US dollars using the consumer price index. We used generalized estimating equations to examine potential predictors of the costs. Monte Carlo simulations and sensitivity analyses were performed to evaluate the varying prevalence and cost of biologic therapy.

Results

The mean total annual direct medical care cost in 2001 for a patient with RA was $9,519. Drug costs were $6,324 (66% of the total), while hospitalization costs were only $1,573 (17%). Approximately 25% of patients received biologic therapy. The mean total annual direct cost for patients receiving biologic agents was $19,016 per year, while the cost for those not receiving biologic therapy was $6,164. RA patients who were in the worst quartile of functional status, as measured by the Health Assessment Questionnaire, experienced direct medical costs for the subsequent year that were $5,022 more than the costs incurred by those in the best quartile. Physical status as determined by the Short Form 36 physical component scale had a similar large effect on RA costs, as did comorbidity. Medical insurance type played a more limited role. However, those without insurance had substantially lower service utilization and costs, and health maintenance organization patients had lower drug costs and total medical costs. Increased years of education, increased income, and majority ethnic status were all associated with increased drug costs but not hospitalization costs. Costs in all categories decreased after age 65 years.

Conclusion

Estimates of direct medical costs for patients with RA are substantially higher than cost estimates before the biologic therapy era, and costs are now driven predominantly by the cost of drugs, primarily biologic agents. RA patients with poor function continue to incur substantially higher costs, as do those with comorbid conditions, and sociodemographic characteristics also play an important role in determination of costs.

     

Small airway disease and its predictors in patients with rheumatoid arthritis

BackgroundRheumatoid arthritis (RA) is a connective tissue disease, characterized by symmetric peripheral polyarthritis. Extra-articular disease occurs in approximately 50% of the patients with lung being a common site. The presence of functional or morphological abnormalities in small airways has recently been noted in patients with RA but its exact prevalence and clinical significance is still a subject of debate. This study was aimed to determine the prevalence of small airway disease (SAD) in patients with RA and the factors influencing it.MethodsFifty consecutive patients with RA were included in this cross-sectional observational study. All patients were subjected to pulmonary function tests (PFT) including Spirometry and Forced Oscillation technique (FOT). Those with features of SAD on PFT were subjected to High-Resolution Computed Tomography (HRCT) of the chest.ResultsSpirometry was suggestive of SAD in 17 patients, with 34% prevalence and FOT was abnormal in 9 patients, with 18% prevalence in the study population. Of 17 patients with SAD on spirometry, 8 (47.05%) patients showed mosaic attenuation, a sign of SAD on the HRCT chest. On univariate analysis, age, Disease Activity Score (DAS-28), joint erosions on X-ray, RF and anti-CCP were found to be associated with SAD.ConclusionSAD was present in one-third of the patients with RA, even in those with short duration of disease, low to moderate disease activity and no respiratory symptoms. It is thus inferred that the complete workup of RA patients should include pulmonary function assessment.     

Mortality predictors among 263 patients with rheumatoid arthritis.

A cohort of 263 patients who completed Health Assessment Questionnaires (HAQ) each year from 1981 to 1989 is examined. Forty-three (43) possible covariates measured in 1981 are considered that might help predict mortality over the 8 years of the study. We use univariate correlation coefficients, stepwise regressions, and survival functions to identify a number of covariates that appear useful for predicting survival: age (-), prednisone use (-), disability index (-), male sex (-), never married (-), penicillamine use (+), divorced (+), and no occupation (-). Our results confirm studies suggesting that the HAQ disability index is a useful prognosticator of length of survival.     

Herpes zoster in patients with rheumatoid arthritis treated with weekly, low-dose methotrexate

PURPOSE: Herpes zoster occurred in nine patients with methotrexate-treated rheumatoid arthritis. We compared these patients to a large group of methotrexate-treated rheumatoid arthritis patients in order to uncover potential factors explaining the occurrence of herpes zoster. PATIENTS AND METHODS: Data from 187 patients taking methotrexate were reviewed and compared with data from another nine patients who developed herpes zoster while taking the drug for rheumatoid arthritis, all from the same university-based arthritis clinic. Literature pertinent to infection in rheumatoid arthritis patients treated with methotrexate is reviewed. RESULTS: Herpes zoster occurred in 14.5 cases per 1,000 patient-years in our methotrexate-treated rheumatoid arthritis patients, as compared with the general population incidence of 1.3 to 4.8 cases per 1,000 patient-years. The infection was unrelated to duration of methotrexate usage, prednisone treatment, or the co-existence of diabetes mellitus, but appeared to occur in patients with high titers of rheumatoid factor and an overall longer duration of rheumatoid arthritis. There were no cases of systemic dissemination or recurrence of herpes zoster despite 27.4 years cumulative follow-up on continued methotrexate therapy. CONCLUSIONS: Herpes zoster may occur more frequently in patients with rheumatoid arthritis treated with low-dose methotrexate than in the general population. Herpes zoster in rheumatoid arthritis patients treated with methotrexate appears to be self-limited, benign, and statistically related to methotrexate use in the presence of longer-term rheumatoid disease.     

Humoral immunity to varicella zoster virus is altered in patients with rheumatoid arthritis

Clinical Rheumatology - The prevalence of herpes zoster (HZ) is high in patients with rheumatologic diseases. The incidence in patients with rheumatoid arthritis (RA) is at least twice as high as...     

HIV seropositivity in patients with herpes zoster

Relationship between zoster and seropositivity for HIV is studied. Serum samples from 66 patients presenting acute zoster infection were tested for HIV antibodies, using ELISA. There was no previous selection of patients, what rendered the population studied unbiased. Seven patients (10.6%) were positive for HIV antibodies. Among them six belonged to AIDS risk groups, all were males and six had ages between 19 and 39 years (mean age value 31.7). Results suggest that the finding of zoster in younger age groups is not necessarily linked to HIV infection. When zoster is diagnosed in patients who belong to AIDS risk groups, independently from their age, the association with HIV infection is statistically significative. In these cases zoster can even be considered as a marker for HIV infection and it is mandatory to test these patients for HIV antibodies.