Rheumatoid Arthritis: Curtis JR

Crawford M, Curtis JR. · No affiliation provided · Curr Rheumatol Rep. · Pubmed #18817643 No free full text.

Abstract: Rheumatoid arthritis patients are at heightened risk for infections because of intrinsic disease severity with associated inflammation, comorbid illnesses, and use of glucocorticoids and various immunosuppressives. Although several studies have reported up to a twofold increase in risk of serious infections in RA patients treated with anti-tumor necrosis factor-alpha agents, results from other studies have been conflicting. Comparing results from different studies is challenging because of differences in patient populations, heterogeneous prevalence of comorbidities, and differing patterns of concomitant medication use. Based on available evidence, an excess risk for infection occurs early after initiation of tumor necrosis factor-alpha inhibitor therapy. Additionally, special circumstances such as surgical procedures may increase infection risk. The appropriate use of biologics in the perioperative setting remains empiric at best.

Danila MI, Patkar NM, Curtis JR, Saag KG, Teng GG. · Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama, USA. · Curr Opin Rheumatol. · Pubmed #18388526 No free full text.

Abstract: PURPOSE OF REVIEW: To summarize the recent literature concerning the role of TNF-alpha in heart failure, epidemiology of heart failure in rheumatoid arthritis and risk of heart failure associated with biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. RECENT FINDINGS: TNF-alpha has been implicated in the pathogenesis of heart failure. It has direct deleterious effects on the myocardium in the setting of acute injury or chronic heart failure. In animal models, TNF-alpha is important in cardiac remodeling, leading to cardiac dysfunction following acute injury. Both incident and worsening heart failure have been reported in patients with rheumatoid arthritis who are treated with anti-TNF-alpha therapy. Recent cohort studies, however, have shown no increased risk and, in some, a protective effect on the risk of heart failure. Certain traditional cardiovascular risk factors have a relatively lesser contribution to cardiovascular morbidity and mortality in patients with rheumatoid arthritis, suggesting that disease-related perturbations of the cytokine network may contribute to the excess risk of heart failure in these patients. SUMMARY: Overall mortality in rheumatoid arthritis has remained stagnant despite advances in rheumatoid arthritis and heart failure management and improved cardiovascular mortality in the general population. Heart failure prevalence is increased in patients with rheumatoid arthritis and leads to greater mortality. Despite current expert consensus contraindicating the use of anti-TNF-alpha agents in patients with moderate to severe heart failure, epidemiological studies in rheumatoid arthritis have not consistently substantiated this association.

Patkar NM, Teng GG, Curtis JR, Saag KG. · Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama 35294-3408, USA. · Curr Opin Rheumatol. · Pubmed #18388525 No free full text.

Abstract: PURPOSE OF REVIEW: Rheumatoid arthritis patients have higher risk for infections due to comorbidities, underlying immunosuppression and use of glucocorticoids and disease modifying antirheumatic drugs. The association between treatment with antitumor necrosis factor alpha agents and serious infections, including opportunistic infections such as tuberculosis, in rheumatoid arthritis patients remains controversial. We present recent literature on this topic with a focus on clinical applications of this new data. RECENT FINDINGS: Prospective cohort studies and population-based registries have described the incidence and risk of serious infections in large rheumatoid arthritis patient populations of antitumor necrosis factor alpha users. Although some studies have suggested a one and one-half to two-fold increased risk, especially immediately after initiating the treatment, not all have shown an elevated risk for serious bacterial infections or tuberculosis. SUMMARY: Although antitumor necrosis factor alpha agents may be independent risk factors for infections there is an absolute low rate of infection in those treated with these agents (approximately 5 per 100 patient-years). Screening for latent tuberculosis with tuberculin skin testing is effective, and compliance with the recommendations for preventing this disease in recipients of antitumor necrosis factor alpha agents has partially decreased the risk of infections. Clinical suspicion toward developing infection in those being treated with antitumor necrosis factor alpha agents, particularly earlier in the treatment course, is important for effective management of patients.

Gaffo A, Saag KG, Curtis JR. · Center for Education and Research and Therapeutics of Musculoskeletal Diseases, University of Alabama at Birmingham, Birmingham, AL, USA. · Am J Health Syst Pharm. · Pubmed #17158693 No free full text.

Abstract: PURPOSE: Current and investigational treatments of rheumatoid arthritis (RA) are described. SUMMARY: The current therapies used to treat RA include nonsteroidal antiinflammatory drugs (NSAIDs), used for the management of pain and inflammation; disease-modifying antirheumatic drugs (DMARDs), used as first-line therapy for all newly diagnosed cases of RA; and biological-response modifiers, targeted agents that selectively inhibit specific molecules of the immune system. Glucocorticoids and other antirheumatic drugs are also used to treat RA. DMARDs include methotrexate, hydroxychloroquine, sulfasalazine, and leflunomide. NSAIDs and glucocorticoids are effective in controlling the pain, inflammation, and stiffness related to RA. Unlike NSAIDs, they slow clinical and radiographic progression of RA. The biological-response modifiers include infliximab, etanercept, and adalimumab (inhibitors of tumor necrosis factor [TNF]-alpha); anakinra, a recombinant inhibitor of interleukin-1; abatacept, the first costimulation blocker; and rituximab, a chimeric anti-CD20 monoclonal antibody. Investigational therapies for RA include anti-interleukin-6-receptor monoclonal antibodies, new TNF-alpha inhibitors (including one for oral administration), and antibodies against proteins critical for B-cell function and survival. Data accumulated in the past decade favor early aggressive therapy for patients suspected of having RA, including early referral to a rheumatologist, new diagnostic techniques, and aggressive therapy with DMARDs, glucocorticoids, and biological agents. The benefits of this approach have been demonstrated in clinical trials. CONCLUSION: Pharmacologic treatments of RA include NSAIDs, glucocorticoids, DMARDs, and biological agents. With an improved understanding of the pathophysiology of RA and the evidence from various clinical trials with the agents, early aggressive therapy with a combination of drugs or biological agents may be warranted for the effective treatment of RA.

Patkar NM, Curtis JR, Teng GG, Allison JJ, Saag M, Martin C, Saag KG. · Center for Education and Research on Therapeutics of Musculoskeletal Disorders, University of Alabama at Birmingham, Birmingham, AL 35294-3408, USA. · J Clin Epidemiol. · Pubmed #18834713 No free full text.

Abstract: OBJECTIVE: To evaluate diagnostic properties of International Classification of Diseases, Version 9 (ICD-9) diagnosis codes and infection criteria to identify bacterial infections among rheumatoid arthritis (RA) patients. STUDY DESIGN AND SETTING: We performed a cross-sectional study of RA patients with and without ICD-9 codes for bacterial infections. Sixteen bacterial infection criteria were developed. Diagnostic properties of comprehensive and restrictive sets of ICD-9 codes and the infection criteria were tested against an adjudicated review of medical records. RESULTS: Records on 162 RA patients with and 50 without purported bacterial infections were reviewed. Positive and negative predictive values of ICD-9 codes ranged from 54%-85% and 84%-100%, respectively. Positive predictive values of the medical records based criteria were 84% and 89% for "definite" and "definite or empirically treated" infections, respectively. Positive predictive value of infection criteria increased by 50% as disease prevalence increased using ICD-9 codes to enhance infection likelihood. CONCLUSION: ICD-9 codes alone may misclassify bacterial infections in hospitalized RA patients. Misclassification varies with the specificity of the codes used and strength of evidence required to confirm infections. Combining ICD-9 codes with infection criteria identified infections with greatest accuracy. Novel infection criteria may limit the requirement to review medical records.

Saag KG, Teng GG, Patkar NM, Anuntiyo J, Finney C, Curtis JR, Paulus HE, Mudano A, Pisu M, Elkins-Melton M, Outman R, Allison JJ, Suarez Almazor M, Bridges SL, Chatham WW, Hochberg M, MacLean C, Mikuls T, Moreland LW, O'Dell J, Turkiewicz AM, Furst DE, Anonymous00442. · University of Alabama, Birmingham, AL, USA. · Arthritis Rheum. · Pubmed #18512708 links to  free full text

This publication has no abstract.

Curtis JR, Xi J, Patkar N, Xie A, Saag KG, Martin C. · University of Alabama at Birmingham, AL, USA. · Arthritis Rheum. · Pubmed #18050253 links to  free full text

This publication has no abstract.

Curtis JR, Kramer JM, Martin C, Saag KG, Patkar N, Shatin D, Burgess M, Xie A, Braun MM. · Center for Education and Research on Therapeutics of Musculoskeletal Disorders, The University of Alabama at Birmingham, Birmingham, AL, USA. · Rheumatology (Oxford). · Pubmed #17938138 links to  free full text

Abstract: OBJECTIVES: New onset heart failure (HF) has been associated with the use of TNF-alpha antagonists etanercept and infliximab based upon spontaneous adverse event reports. HF clinical trials of these agents were stopped early due to futility or worsening of existing HF. A potential association between etanercept and infliximab and new onset HF has been studied minimally at a population level. METHODS: Using administrative claims from a large U.S. health care organization, we identified rheumatoid arthritis (RA) and Crohn's disease (CD) patients receiving infliximab or etanercept (exposed), and comparator cohorts of RA and CD patients receiving non-biologic immunosuppressives (unexposed). We studied adults < 50 years to reduce potential confounding related to common age-related comorbidities. Based on abstracted medical records of suspected HF cases, a physician panel adjudicated cases as definite, possible or no HF. RESULTS: Among 4018 RA and CD patients with mean duration follow-up of 18 months, 9 of 33 suspected HF cases (identified using claims data) were adjudicated as definite (n = 5) or possible (n = 4) HF. The relative risk of HF among TNF-alpha antagonist-treated RA and CD patients was 4.3 and 1.2, respectively (P = NS for both). The absolute difference in cumulative incidence of HF among infliximab or etanercept-exposed compared to unexposed patients was 3.4 and 0.3 cases per 1000 persons for RA and CD (P = NS), respectively, yielding a number needed to harm of 294 for RA and 3333 for CD. CONCLUSION: We found only a small number of presumed HF cases (n = 9, or 0.2%) in a large population of relatively young RA and CD patients. Although there was an increased relative risk of incident, HF that was not statistically significant among those exposed to TNF-alpha antagonists compared to those unexposed, larger cohorts are needed to provide more precise risk estimates and permit adjustment for potential confounding.

Curtis JR, Patkar N, Xie A, Martin C, Allison JJ, Saag M, Shatin D, Saag KG. · University of Alabama at Birmingham, Center for Education and Research on Therapeutics, AL 35294, USA. · Arthritis Rheum. · Pubmed #17393394 links to  free full text

Abstract: OBJECTIVE: To evaluate the risk of serious bacterial infections associated with tumor necrosis factor alpha (TNFalpha) antagonists among rheumatoid arthritis (RA) patients. METHODS: A retrospective cohort study of US RA patients enrolled in a large health care organization identified patients who received either TNFalpha antagonists or methotrexate (MTX). Administrative data were used to identify hospitalizations with possible bacterial infections; corresponding medical records were abstracted and reviewed by infectious disease specialists for evidence of definite infections. Proportional hazards models evaluated time-dependent infection risks associated with TNFalpha antagonists. RESULTS: Hospital medical records with claims-identified suspected bacterial infections were abstracted (n=187) among RA patients who received TNFalpha antagonists (n=2,393; observation time 3,894 person-years) or MTX (n=2,933; 4,846 person-years). Over a median followup time of 17 months, the rate of hospitalization with a confirmed bacterial infection was 2.7% among the patients treated with TNFalpha antagonists compared with 2.0% among the patients treated with MTX only. The multivariable-adjusted hazard ratio (HR) of infection among the patients who received TNFalpha antagonists was 1.9 (95% confidence interval [95% CI] 1.3-2.8) compared with patients who received MTX only. The incidence of infections was highest within 6 months after initiating TNFalpha antagonist therapy (2.9 versus 1.4 infections per 100 person-years; multivariable-adjusted HR 4.2, 95% CI 2.0-8.8). CONCLUSION: The multivariable-adjusted risk of hospitalization with a physician-confirmed definite bacterial infection was approximately 2-fold higher overall and 4-fold higher in the first 6 months among patients receiving TNFalpha antagonists versus those receiving MTX alone. RA patients were at increased risk of serious infections, irrespective of the method used to define an infectious outcome. Patients and physicians should vigilantly monitor for signs of infection when using TNFalpha antagonists, particularly shortly after treatment initiation.

Curtis JR, Martin C, Saag KG, Patkar NM, Kramer J, Shatin D, Allison J, Braun MM. · University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. · Arthritis Rheum. · Pubmed #17330283 links to  free full text

This publication has no abstract.

Shatin D, Rawson NS, Curtis JR, Braun MM, Martin CK, Moreland LW, Becker AF, Patkar NM, Allison JJ, Saag KG. · Center for Health Care Policy and Evaluation, Minneapolis, MN, USA. · Pharmacoepidemiol Drug Saf. · Pubmed #16136625 No free full text.

Abstract: PURPOSE: Following its licensure, tuberculosis (TB) was reported as a potential adverse effect of infliximab. Subsequently, the product circular was changed to recommend tuberculin skin testing before patients received infliximab, which was reinforced by several risk communication efforts. The aim of this study was to evaluate patterns and predictors of documented tuberculin skin testing in patients before and after manufacturer, federal, and academic risk communications. METHODS: Patients administered infliximab were identified from 11 health plans located throughout the United States, and claims data were examined to determine whether the patients had received a tuberculin skin test. Patients were divided into three cohorts depending on the timing of their first infliximab treatment in relation to the risk communication efforts. RESULTS: The overall tuberculin skin testing rate doubled from 15.4% in the first cohort to 30.9% in the last cohort, while the rate of pre-infliximab treatment testing increased from 0 to 27.7% (Chi-squared test for trend, p < 0.0001 for both). Tuberculin skin testing rates were significantly higher in women, those with a diagnosis of rheumatoid or psoriatic arthritis, and those with a rheumatologist as prescriber. After multivariable analysis, only rheumatologist remained significantly associated with tuberculin skin testing. CONCLUSIONS: Although the tuberculin skin testing rate was relatively low overall, tuberculin skin testing doubled over 30 months of ongoing risk communication efforts and under ascertainment likely occurred. We also found variation in the tuberculin skin testing rate associated with physician specialty. This study demonstrates a significant change in patient care following risk communication efforts.