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IMPORTANCE - Herpes zoster reactivation disproportionately affects patients with rheumatoid arthritis (RA). It is unclear whether anti-tumor necrosis factor (anti-TNF) therapy elevates herpes zoster risk.
OBJECTIVES - To ascertain whether initiation of anti-TNF therapy compared with nonbiologic comparators is associated with increased herpes zoster risk.
DESIGN, SETTING, AND PATIENTS - We identified new users of anti-TNF therapy among cohorts of patients with RA, inflammatory bowel disease, and psoriasis, psoriatic arthritis, or ankylosing spondylitis from 1998 through 2007 within a large US multi-institutional collaboration combining data from Kaiser Permanente Northern California, Pharmaceutical Assistance Contract for the Elderly, Tennessee Medicaid, and national Medicaid/Medicare programs. We compared herpes zoster incidence between new anti-TNF users (n=33,324) and patients initiating nonbiologic disease-modifying antirheumatic drugs (DMARDs) (n=25,742) within each inflammatory disease cohort (last participant follow-up December 31, 2007). Within these cohorts, we used Cox regression models to compare propensity score-adjusted herpes zoster incidence between new anti-TNF and nonbiologic DMARD users while controlling for baseline corticosteroid use.
MAIN OUTCOME MEASURES - Incidence of herpes zoster cases occurring after initiation of new anti-TNF or nonbiologic DMARD therapy.
RESULTS - Among 33,324 new users of anti-TNF therapy, we identified 310 herpes zoster cases. Crude incidence rates among anti-TNF users were 12.1 per 1000 patient-years (95% CI, 10.7-13.6) for RA, 11.3 per 1000 patient-years (95% CI, 7.7-16.7) for inflammatory bowel disease, and 4.4 per 1000 patient-years (95% CI, 2.8-7.0) for psoriasis, psoriatic arthritis, or ankylosing spondylitis. Baseline use of corticosteroids of 10 mg/d or greater among all disease indications was associated with elevated risk (adjusted hazard ratio [HR], 2.13 [95% CI, 1.64-2.75]) compared with no baseline use. For patients with RA, adjusted incidence rates were similar between anti-TNF and nonbiologic DMARD initiators (adjusted HR, 1.00 [95% CI, 0.77-1.29]) and comparable between all 3 anti-TNF therapies studied. Across all disease indications, the adjusted HR was 1.09 (95% CI, 0.88-1.36).
CONCLUSION AND RELEVANCE - Among patients with RA and other inflammatory diseases, those who initiated anti-TNF therapies were not at higher risk of herpes zoster compared with patients who initiated nonbiologic treatment regimens.
OBJECTIVE - To compare incidence rates of selected opportunistic infections among children with and children without juvenile idiopathic arthritis (JIA).
METHODS - Using U.S. national Medicaid administrative claims data from 2000 through 2005, we identified a cohort of children with JIA based on physician diagnosis codes and dispensed medications. We also identified a non-JIA comparator cohort of children diagnosed as having attention deficit hyperactivity disorder (ADHD). We defined 15 types of opportunistic infection using physician diagnosis or hospital discharge codes; criteria for 7 of these types also included evidence of treatment with specific antimicrobial agents. We calculated infection incidence rates. The rates in the ADHD comparator cohort were standardized to the age, sex, and race distribution of the JIA cohort. We calculated incidence rate ratios (IRRs) with 95% confidence intervals (95% CIs) to compare infection rates.
RESULTS - The JIA cohort included 8,503 children with 13,990 person-years of followup. The ADHD comparator cohort included 360,362 children with 477,050 person-years of followup. When all opportunistic infections were considered together as a single outcome, there were 42 infections in the JIA cohort (incidence rate 300 per 100,000 person-years; IRR 2.4 [95% CI 1.7-3.3] versus ADHD). The most common opportunistic infections among children with JIA were 3 cases of Coccidioides (incidence rate 21 per 100,000 person-years; IRR 101 [95% CI 8.1-5,319] versus ADHD), 5 cases of Salmonella (incidence rate 35 per 100,000 person-years; IRR 3.8 [95% CI 1.2-9.5]), and 32 cases of herpes zoster (incidence rate 225 per 100,000 person-years; IRR 2.1 [95% CI 1.4-3.0]).
CONCLUSION - Opportunistic infections are rare among children with JIA. Nevertheless, children with JIA had a higher rate of opportunistic infections, including an increased rate of Coccidioides, Salmonella, and herpes zoster compared to children with ADHD.
Copyright © 2013 by the American College of Rheumatology.
OBJECTIVE - We tested the hypothesis that initiation of tumor necrosis factor α (TNFα) antagonists reduced the risk of fractures compared to nonbiologic comparators in patients with autoimmune diseases.
METHODS - Using 4 large administrative databases, we assembled retrospective cohorts of patients with autoimmune diseases who initiated either a TNFα antagonist or a nonbiologic medication. We identified 3 mutually exclusive disease groups: rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and a combined group: psoriasis (PsO), psoriatic arthritis (PsA), or ankylosing spondylitis (AS). We used baseline covariate data to calculate propensity scores (PS) for each disease group and used Cox regression to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs). We compared the risk of combined hip, radius/ulna, humerus, or pelvic fractures between PS-matched cohorts of new users of TNFα antagonists and nonbiologic comparators.
RESULTS - We identified 9,020, 2,014, and 2,663 new PS-matched episodes of TNFα antagonist and nonbiologic comparator use in RA, IBD, and PsO-PsA-AS cohorts, respectively. The risk of combined fractures was similar between new users of TNFα antagonists and nonbiologic comparators for each disease (HR 1.17, 95% CI 0.91-1.51; HR 1.49, 95% CI 0.72-3.11; and HR 0.92, 95% CI 0.47-1.82 for RA, IBD, and PsO-PsA-AS, respectively). In RA, the risk of combined fractures was associated with an average daily dosage of prednisone equivalents >10 mg/day at baseline compared with no glucocorticoid (HR 1.54, 95% CI 1.03-2.30).
CONCLUSION - The risk of fractures did not differ between initiators of a biologic agent and a nonbiologic comparator for any disease studied. Among RA patients, use of >10 mg/day of prednisone equivalents at baseline increased the fracture risk.
Copyright © 2013 by the American College of Rheumatology.
BACKGROUND - While heart failure (HF) is associated with elevations in tumor necrosis factor (TNF)α, several trials of TNF antagonists showed no benefit and possibly worsening of disease in those with known severe HF. We studied the risk of new or recurrent HF among a group of patients receiving these agents to treat rheumatoid arthritis (RA).
METHODS - We used data from four different US healthcare programmes. Subjects with RA receiving methotrexate were eligible to enter the study cohort if they added or switched to a TNF antagonist or another non-biological disease modifying antirheumatic drug (nbDMARD). These groups were compared in Cox regression models stratified by propensity score decile and adjusted for oral glucocorticoid dosage, prior HF hospitalisations, and the use of loop diuretics.
RESULTS - We compared 8656 new users of a nbDMARD with 11 587 new users of a TNF antagonist with similar baseline covariates. The HR for the TNF antagonists compared with nbDMARD was 0.85 (95% CI 0.63 to 1.14). The HR was also not elevated in subjects with a history of HF. But, it was elevated prior to 2002 (HR 2.17, 95% CI 0.45 to 10.50, test for interaction p=0.036). Oral glucocorticoids were associated with a dose-related gradient of HF risk: compared with no use, 1≤5 mg HR 1.30 (95% CI 0.91 to 1.85), ≥5 mg HR 1.54 (95% CI 1.09 to 2.19).
CONCLUSIONS - TNF antagonists were not associated with a risk of HF hospital admissions compared with nbDMARDs in this RA population.
There have been numerous changes regarding evidence-based care of patients with rheumatoid arthritis, a costly, chronic, autoimmune disease. This article provides an update on the factors that affect the safe use of biologic medications in this patient population.
PURPOSE - To evaluate the incidence of optic neuritis (ON) in patients using anti-tumor necrosis factor (TNF) alpha therapy.
DESIGN - Retrospective, population-based cohort study.
METHODS - We identified new users of anti-TNF therapy (etanercept, infliximab, or adalimumab) or nonbiologic disease-modifying antirheumatic drugs (DMARDs) during 2000-2007 from the following data sources: Kaiser Permanente Northern California, Pharmaceutical Assistance Contract for the Elderly, Tennessee Medicaid, and National Medicaid/Medicare. Within this cohort, we used validated algorithms to identify ON cases occurring after onset of new drug exposure. We then calculated and compared ON incidence rates between exposure groups.
RESULTS - We identified 61 227 eligible inflammatory disease patients with either new anti-TNF or new nonbiologic DMARD use. Among this cohort, we found 3 ON cases among anti-TNF new users, occurring a median of 123 days (range, 37-221 days) after anti-TNF start. The crude incidence rate of ON across all disease indications among anti-TNF new users was 10.4 (95% CI 3.3-32.2) cases per 100 000 person-years. In a sensitivity analysis considering current or past anti-TNF or DMARD use, we identified a total of 6 ON cases: 3 among anti-TNF users and 3 among DMARD users. Crude ON rates were similar among anti-TNF and DMARD groups: 4.5 (95% CI 1.4-13.8) and 5.4 (95% CI 1.7-16.6) per 100 000 person-years, respectively.
CONCLUSION - Optic neuritis is rare among those who initiate anti-TNF therapy and occurs with similar frequency among those with nonbiologic DMARD exposure.
Copyright © 2013 Elsevier Inc. All rights reserved.
OBJECTIVE - To evaluate whether rates of serious infection with anti-tumor necrosis factor (anti-TNF) therapy in rheumatoid arthritis (RA) patients differ in magnitude by specific drugs and patient characteristics.
METHODS - Among new nonbiologic disease-modifying antirheumatic drug users enrolled in Medicare and Medicaid or a large US commercial health plan, we created and validated a person-specific infection risk score based on age, demographics, insurance type, glucocorticoid dose, and comorbidities to identify patients at high risk for hospitalized infections. We then applied this risk score to new users of infliximab, etanercept, and adalimumab and compared the observed 1-year rates of infection to one another and to the predicted infection risk score estimated in the absence of anti-TNF exposure.
RESULTS - Among 11,657 RA patients initiating anti-TNF therapy, the observed 1-year rate of infection was 14.2 infections per 100 person-years in older patients (age ≥65 years) and 4.8 in younger patients (age <65 years). There was a relatively constant rate difference of ~1-4 infections per 100 person-years associated with anti-TNF therapy across the range of the infection risk score. Infliximab had a significantly greater adjusted rate of infection compared to etanercept and adalimumab in both high- and lower-risk RA patients.
CONCLUSION - The rate of serious infections for anti-TNF agents was incrementally increased by a fixed absolute difference irrespective of age, comorbidities, and other factors that contributed to infections. Older patients and those with high comorbidity burdens should be reassured that the magnitude of their incremental risk with anti-TNF agents is not greater than for lower-risk patients.
Copyright © 2012 by the American College of Rheumatology.
OBJECTIVES - To devise a patient-perspective driven measure of the quality of patient-health care provider communication and to evaluate the psychometric properties of this scale in a sample of 150 patients with rheumatoid arthritis.
METHODS - Items were developed from interviews with 15 patients with rheumatoid arthritis. Two rheumatologists, a behavioral scientist, and a nurse researcher provided item feedback. Exploratory factor analysis with Oblimin rotation was used to examine the dimensionality of the newly developed Patient-Health Care Provider Communication Scale (PHCPCS). Cronbach's alpha was computed to assess internal consistency. Test-retest reliability was determined using the intraclass correlation coefficient. Construct validity was tested by comparing the PHCPCS with the Perceived Involvement in Care Scale (PICS) using correlation analysis.
RESULTS - The PHCPCS measured two dimensions of the quality of patient-health care provider communication [Quality Communication (α = 0.94) and Negative Patient-Health Care Provider Communication (α = 0.73)]. The total PHCPCS score and its Quality Communication Subscale were positively correlated with the total score on the PICS and with the doctor facilitation subscale of the PICS.
DISCUSSION - This new measure of the quality of patient-health care provider communication has the potential for use in clinical practice, provider education, and further studies to improve health care to patients with rheumatoid arthritis.
PURPOSE - Previous studies suggest that disease-modifying anti-rheumatic drugs (DMARDs) increase tuberculosis (TB) risk. The accuracy of pharmacy and coded-diagnosis information to identify persons with TB is unclear.
METHODS - Within a cohort of rheumatoid arthritis (RA) patients (2000-2005) enrolled in Tennessee Medicaid, we identified those with potential TB using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD9-CM) diagnosis codes and/or pharmacy claims. Using the Tennessee TB registry as the gold standard for identification of TB, we estimated the sensitivity, specificity, predictive values, and the respective 95% confidence intervals for each TB case-ascertainment strategy.
RESULTS - Ten of 18,094 RA patients had confirmed TB during 61,461 person-years of follow-up (16.3 per 100,000 person-years). The sensitivity and positive predictive value (PPV) and respective 95% confidence intervals were low for confirmed TB based on ICD9-CM codes alone (60.0% (26.2-87.8) and 1.3% (0.5-2.9)), pharmacy data alone (20% (2.5-55.6) and 4.1% (0.5-14.3)), and both (20% (2.5-55.6) and 25.0% (3.2-65.1)).
CONCLUSIONS - Algorithms that use administrative data alone to identify TB have a poor PPV that results in a high false positive rate of TB detection.
Copyright © 2012 John Wiley & Sons, Ltd.
PURPOSE - Infliximab, a chimeric monoclonal anti-TNFα antibody, has been found to increase the risk of serious infections compared with the TNF receptor fusion protein etanercept in some studies. It is unclear whether the risk varies by patient characteristics. We conducted a study to address this question.
METHODS - We identified members of Kaiser Permanente Northern California who initiated infliximab (n = 793) or etanercept (n = 2692) in 1997-2007. Using a Cox model, we estimated the propensity-score-adjusted hazard ratio (HR) and 95% confidence interval (CI) of serious infections requiring hospitalization or opportunistic infections comparing infliximab initiators to etanercept initiators. We tested whether the adjusted HR differed by age, sex, race/ethnicity, body mass index, and smoking status.
RESULTS - The crude incidence rate of serious infections per 100 person-years was 5.4 (95%CI: 3.8, 7.5) in patients <65 years and 16.0 (95%CI: 10.4, 23.4) in patients ≥ 65 years during the first 3 months following treatment initiation. Compared with etanercept, the adjusted HR during this period was elevated for infliximab in patients <65 years (HR: 3.01; 95%CI: 1.49, 6.07), but not in those ≥ 65 years (HR 0.94; 95%CI: 0.41, 2.13). Findings did not suggest that the HR varied by the other patient characteristics examined.
CONCLUSIONS - An increased risk of serious infections associated with infliximab relative to etanercept did not appear to be modified by patients' sex, race/ethnicity, body mass index, or smoking status. There was an indication that the increased risk might be limited to patients <65 years. Additional studies are warranted to verify or refute this finding.
Copyright © 2012 John Wiley & Sons, Ltd.