Use of a disease risk score to compare serious infections associated with anti-tumor necrosis factor therapy among high- versus lower-risk rheumatoid arthritis patients.

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.

The use, safety, and effectiveness of herpes zoster vaccination in individuals with inflammatory and autoimmune diseases: a longitudinal observational study.

INTRODUCTION: Zostavax, a live attenuated vaccine, has been approved in the United States for use in older individuals to reduce the risk and severity of herpes zoster (HZ), also known as shingles. The vaccine is contraindicated in individuals taking anti-tumor necrosis factor alpha (anti-TNF) therapies or other biologics commonly used to treat autoimmune diseases because of the safety concern that zoster vaccine may be associated with a short-term HZ risk. The objective of the study was to examine the use, safety (short-term HZ risk after vaccination), and effectiveness of zoster vaccine in individuals with rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, and/or inflammatory bowel diseases. METHODS: We conducted a cohort study of patients aged 50 years and older with rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, and/or inflammatory bowel diseases by using administrative claims data from a nationwide health plan from January 1, 2005, to August 31, 2009. We examined the extent to which zoster vaccine was used; assessed factors associated with vaccine use (Cox proportional hazards regression); and compared the incidence rates of herpes zoster (HZ) between vaccinated and unvaccinated patients. RESULTS: Among 44,115 patients with the autoimmune diseases, 551 (1.2%) received zoster vaccine, and 761 developed HZ. Zoster vaccine use increased continuously after approval in 2006. Younger and healthier patients, those who had an HZ infection within the past 6 months, and those who were not using anti-TNF therapies were more likely to receive the vaccine. Approximately 6% of vaccinated patients were using anti-TNF therapies at the time of vaccination. The incidence rates of HZ were similar in vaccinated and unvaccinated patients (standardized incidence ratio, 0.99; 95% confidence interval, 0.29 to 3.43). CONCLUSIONS: Use of the zoster vaccine was uncommon among older patients with autoimmune diseases, including those not exposed to immunosuppressive medications. The short-term risk of HZ did not appear to be increased in vaccinated patients, even among those using immunosuppressive therapies (for example, biologics) at the time of vaccination. However, our study was limited by the small number of vaccinated patients, and further evidence is needed to confirm the vaccine's safety and efficacy in this population.

The comparative risk of serious infections among rheumatoid arthritis patients starting or switching biological agents.

BACKGROUND: It is unclear whether anti-tumour necrosis factor alpha and biological agents with different mechanisms of action have similar safety. This study evaluated the incidence of hospitalised infections among rheumatoid arthritis (RA) patients starting or switching various biological agents. METHODS: Using a database from a large US healthcare organisation from January 2005 to August 2009, the authors identified enrollees with RA and their treatment episodes entailing the new use of a biological agent, stratified by no biological use in the previous year ('biological-free') or switching from a different biological agent ('switchers'). Outcomes were hospitalised infections identified using previously validated algorithms. Proportional hazards models estimated the hazard ratio of hospitalised infections, comparing each biological agent with infliximab. RESULTS: Among 7847 biological treatment episodes, 63% were for biological-free patients and 37% for switchers. There were 364 hospitalised infections. Rates of hospitalised infection among biological-free patients and switchers were 4.6 and 7.0 per 100 person-years, respectively (p<0.0001). After multivariable adjustment controlling for biological-free/switcher status and other infection-related factors and compared with infliximab, users of abatacept (HR 0.68, 95% CI 0.48 to 0.96), adalimumab (HR 0.52, 0.39 to 0.71), etanercept (HR 0.64, 0.49 to 0.84) and rituximab (HR 0.81, 0.55 to 1.20) had lower rates of hospitalised infection. Patient risk factors contributed more to the risk of infection than did the risk associated with specific biological therapies. CONCLUSION: The rate of hospitalised infections among RA patients was highest for infliximab. Most of the variability in patients' risk of infection was driven by factors other than biological agent exposure.

The incidence of gastrointestinal perforations among rheumatoid arthritis patients.

OBJECTIVE: Gastrointestinal (GI) perforation has emerged as a novel safety concern in relation to medications used to treat rheumatoid arthritis (RA). This study was undertaken to characterize the incidence and risk factors for GI perforation in RA patients. METHODS: Using administrative databases of a large US health plan, we identified RA patients treated with biologic agents, methotrexate (MTX), oral glucocorticoids, and nonsteroidal antiinflammatory drugs (NSAIDs). Additional risk factors we evaluated included diverticulitis. Hospitalization with GI perforation was identified using a validated algorithm. Incidence rates and risk factors were evaluated using Cox proportional hazards models. RESULTS: Among 40,841 RA patients, 37 hospitalizations with GI perforation were identified. The rate of GI perforation among patients currently being treated with biologic agents who were also receiving oral glucocorticoids was higher (1.12 per 1,000 person-years [95% confidence interval (95% CI) 0.50-2.49]) than for patients being treated with biologic agents who were not also receiving glucocorticoids (0.47 per 1,000 person-years [95% CI 0.22-0.98]) or for patients being treated with MTX who were also receiving glucocorticoids (0.87 per 1,000 person-years [95% CI 0.36-2.10]). Neither biologic agents nor MTX was significantly associated with GI perforation, in contrast to current treatment with glucocorticoids and NSAIDs together (hazard ratio 4.7 [95% CI 1.9-12.0]) or glucocorticoids alone (hazard ratio 2.8 [95% CI 1.3-6.1]). Diverticulitis also was a strong risk factor (hazard ratio 9.1 [95% CI 3.1-26.4]). Seventy percent of patients with GI perforation received glucocorticoids, had antecedent diverticulitis, or both. CONCLUSION: GI perforation is an uncommon but serious adverse event among RA patients. Because a majority of patients with GI perforation were being treated with glucocorticoids or had previously experienced diverticulitis, these individuals should be considered at higher risk.