Amy S. Mudano

2012 Update of the 2008 American College of Rheumatology recommendations for the use of disease‐modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis

The American College of Rheumatology (ACR) most recently published recommendations for use of disease modifying anti-rheumatic drugs (DMARDs) and biologics in the treatment of rheumatoid arthritis (RA) in 2008 (1). These recommendations covered indications for use, monitoring of side-effects, assessment of the clinical response to DMARDs and biologics, screening for tuberculosis (TB), and assessment of the roles of cost and patient preference in decision-making for biologic agents (1). Recognizing the rapidly evolving knowledge in RA management and the accumulation of new evidence regarding the safety and efficacy of existing and newer therapies, the ACR commissioned an update of the 2008 recommendations in select topic areas. The 2012 revision updates the 2008 ACR recommendations in the following areas: (1) indications for DMARDs and biologics; (2) switching between DMARD and biologic therapies; (3) use of biologics in high-risk patients (those with hepatitis, congestive heart failure, and malignancy); (4) screening for TB in patients starting or currently receiving biologics; and (5) vaccination in patients starting or currently receiving DMARDs or biologics (Table 1). Table 1 Overview Comparison of Topics and Medications Included in the 2008 and 2012 ACR RA Recommendations METHODS We utilized the same methodology as described in detail in the 2008 guidelines (1) to maintain consistency and to allow cumulative evidence to inform this 2012 recommendation update. These recommendations were developed by two expert panels: (1) a non-voting working group and Core Expert Panel (CEP) of clinicians and methodologists responsible for the selection of the relevant topic areas to be considered, the systematic literature review, and the evidence synthesis and creation of “clinical scenarios”; and (2) a Task Force Panel (TFP) of 11 internationally-recognized expert clinicians, patient representatives and methodologists with expertise in RA treatment, evidence-based medicine and patient preferences who were tasked with rating the scenarios created using an ordinal scale specified in the Research and Development/University of California at Los Angeles (RAND/UCLA) Appropriateness method (2–4). This method solicited formal input from a multi-disciplinary TFP panel to make recommendations informed by the evidence. The methods used to develop the updated ACR recommendations are described briefly below. Systematic Literature Review – Sources, Databases and Domains Literature searches for both DMARDs and biologics relied predominantly on PubMed searches) with medical subject headings (MeSH) and relevant keywords similar to those used for the 2008 ACR RA recommendations (see Appendices 1 and 2). We included randomized clinical trials (RCTs), controlled clinical trials (CCTs), quasi-experimental designs, cohort studies (prospective or retrospective), and case-control studies, with no restrictions on sample size. More details about inclusion criteria are listed below and in Appendix 3. The 2008 recommendations were based on a literature search that ended on February 14, 2007. The literature search end date for the 2012 Update was February 26, 2010 for the efficacy and safety studies and September 22, 2010 for additional qualitative reviews related to TB screening, immunization and hepatitis (similar to the 2008 methodology). Studies published subsequent to that date were not included. For biologics, we also reviewed the Cochrane systematic reviews and overviews (published and in press) in the Cochrane Database of Systematic Reviews to identify additional studies (5–8) and further supplemented by hand-checking the bibliographies of all included articles. Finally, the CEP and TFP confirmed that relevant literature was included for evidence synthesis. Unless they were identified by the literature search and met the article inclusion criteria (see Appendix 3), we did not review any unpublished data from product manufacturers, investigators, or the Food and Drug Administration (FDA) Adverse Event Reporting System. We searched the literature for the eight DMARDs and nine biologics most commonly used for the treatment of RA. Literature was searched for eight DMARDS including azathioprine, cyclosporine, hydroxychloroquine, leflunomide, methotrexate, minocycline, organic gold compounds and sulfasalazine. As in 2008, azathioprine, cyclosporine and gold were not included in the recommendations based on infrequent use and lack of new data (Table 1). Literature was searched for nine biologics including abatacept, adalimumab, anakinra, certolizumab pegol, etanercept, golimumab, infliximab, rituximab and tocilizumab; anakinra was not included in the recommendations due to infrequent use and lack of new data. Details of the bibliographic search strategy are listed in Appendix 1.

American College of Rheumatology 2008 Recommendations for the Use of Nonbiologic and Biologic Disease-Modifying Antirheumatic Drugs in Rheumatoid Arthritis

Guidelines and recommendations developed and/or endorsed by the American College of Rheumatology (ACR) are intended to provide guidance for particular patterns of practice and not to dictate the care of a particular patient. The ACR considers adherence to these guidelines and recommendations to be voluntary, with the ultimate determination regarding their application to be made by the physician in light of each patient’s individual circumstances. Guidelines and recommendations are intended to promote beneficial or desirable outcomes but cannot guarantee any specific outcome. Guidelines and recommendations developed or endorsed by the ACR are subject to periodic revision as warranted by the evolution of medical knowledge, technology, and practice.

Cigarette smoking and the risk of rheumatoid arthritis among postmenopausal women: Results from the Iowa Women's Health Study

PURPOSE To determine whether cigarette smoking increases the risk of rheumatoid arthritis among postmenopausal women. SUBJECTS AND METHODS We followed a cohort of 31 336 women in Iowa who were aged 55 to 69 years in 1986 and who had no history of rheumatoid arthritis. Through 1997, 158 cases of rheumatoid arthritis were identified and validated based on review of medical records and supplementary information provided by physicians. Multivariable Cox proportional hazards regression was used to derive rate ratios (RRs) and 95% confidence intervals (CIs) for the association between cigarette smoking and rheumatoid arthritis. RESULTS Compared with women who had never smoked, women who were current smokers (RR = 2.0; 95% CI: 1.3 to 2.9) or who had quit 10 years or less before study baseline (RR = 1.8; 95% CI: 1.1 to 3.1) were at increased risk of rheumatoid arthritis, but women who had quit more than 10 years before baseline were not at increased risk (RR = 0.9; 95% CI: 0.5 to 2.6). Both the duration and intensity of smoking were associated with rheumatoid arthritis. Multivariable adjustments for age, marital status, occupation, body mass index, age at menopause, oral contraceptive use, hormone replacement therapy, alcohol use, and coffee consumption did not alter these results. CONCLUSION These results suggest that abstinence from smoking may reduce the risk of rheumatoid arthritis among postmenopausal women.

Coffee, tea, and caffeine consumption and risk of rheumatoid arthritis: Results from the Iowa Women's Health Study

OBJECTIVE To evaluate whether coffee, tea, and caffeine consumption are risk factors for rheumatoid arthritis (RA) onset among older women. METHODS These factors were evaluated in a prospective cohort study that was initiated in 1986 and that included 31,336 women ages 55-69 years without a history of RA. Risk factor data were self-reported using a mailed questionnaire. Through 1997, 158 cases of RA were identified and validated against medical records. The relative risk (RR) and 95% confidence interval (95% CI) were used as the measures of association and were adjusted for age, alcohol use, smoking history, age at menopause, marital status, and the use of hormone replacement therapy. RESULTS Compared with those reporting no use, subjects drinking > or =4 cups/day of decaffeinated coffee were at increased risk of RA (RR 2.58, 95% CI 1.63-4.06). In contrast, women consuming >3 cups/day of tea displayed a decreased risk of RA (RR 0.39, 95% CI 0.16-0.97) compared with women who never drank tea. Caffeinated coffee and daily caffeine intake were not associated with the development of RA. Multivariable adjustment for a number of potential confounders did not alter these results. The associations of RA onset with the highest categories of decaffeinated coffee consumption (RR 3.10, 95% CI 1.75-5.48) and tea consumption (RR 0.24, 95% CI 0.06-0.98) were stronger in women with seropositive disease compared with those with seronegative disease (RR 1.54, 95% CI 0.62-3.84 and RR 0.93, 95% CI 0.27-3.20, respectively). CONCLUSION Decaffeinated coffee intake is independently and positively associated with RA onset, while tea consumption shows an inverse association with disease onset. Further investigations of decaffeinated coffee and tea intake as arthritis risk factors are needed to verify these findings and explore their biologic basis.

Identification and Validation of Vertebral Compression Fractures using Administrative Claims Data

Introduction:Vertebral compression fractures (VCFs) are the most common type of osteoporotic fracture. Administrative claims data might be useful to identify VCFs, but this approach to case finding has received limited evaluation. Methods:Using the administrative claims databases of a large regional US health care organization, we identified adults with a claim with a VCF diagnosis code from January 2003 to June 2004 and excluded persons with malignancy. We examined the positive predictive values (PPV) of several claims algorithms to correctly identify any confirmed (prevalent or incident) VCF, and separately, incident VCFs. Results:A total of 259 persons were identified with a VCF suspected based on their administrative claims data. A claims algorithm that required a VCF diagnosis on any claim had a PPV to identify any confirmed VCF of 87% (95% confidence interval (CI), 82–91%). The PPV of this algorithm to identify a confirmed incident VCF was 46% (95% CI, 37–54%). An algorithm that required a spine imaging test followed by a physician visit with a VCF code within 10 days, or a hospitalization with a primary diagnosis code, had higher PPVs (PPV = 93%; 95% CI, 87–98% for any confirmed VCF; PPV = 61%; 95% CI, 49–74% for incident VCFs). Conclusions:A simple case finding approach to identify VCFs using administrative claims data can identify prevalent VCFs with high accuracy but misclassified more than half of incident VCFs. A more complex claims algorithm may be used but still will result in some misclassification of incident VCFs.

Racial disparities in osteoporosis prevention in a managed care population

Background Osteoporosis in black women may result in increased disability, longer hospital stays, and higher mortality compared with white women. However, it is unknown whether osteoporosis treatment or bone mineral density (BMD) measurement is different in these women, particularly in those at highest risk. Methods To examine differences and determinants of osteoporosis preventive interventions among white and black women in a large regional health maintenance organization, women 50 years of age and older were surveyed (n = 8,909) to determine their receipt of BMD testing and medical therapies for osteoporosis prevention. Results After adjusting for potential confounders, black women had two- to threefold lower odds of BMD test or osteoporosis prescription treatment. Even among women with a previous fracture, blacks still had a significantly lower likelihood of both BMD testing and prescription therapy. Conclusion Compared with whites, black women reported significantly less BMD testing and prescription and nonprescription osteoporosis therapy. This disparity was not fully explained by other demographic or risk factor differences.

Preferences for Fractures and Other Glucocorticoid-Associated Adverse Effects among Rheumatoid Arthritis Patients

Objective. The objective of this study was to determine rheumatoid arthritis (RA) patients’ preferences for validated health state scenarios depicting glucocorticoid adverse events, predictors of these preferences, and psychometric properties of different preference techniques in this population. Methods. Preferences were elicited by rating scale and time trade-off methods. Time trade-offs included trading current health for either time spent alive in an adverse health state for chronic conditions (time trade-off) or time spent in a sleeplike state for acute conditions (sleep trade-off). Results. A total of 107 subjects with long-standing RA participated in the preference interviews. Mean preference values (rating scale/trade-off) were lowest for serious fracture adverse events, including hip fracture requiring a nursing home stay (0.55 ± 0.22/0.76 ± 0.36) and vertebral fracture with chronic pain (0.59 ± 0.23/0.67 ± 0.35), and highest for cataracts (0.84 ± 0.17/0.96 ± 0.09) and wrist fracture (0.82 ± 0.18/0.81 ± 0.29). Rating scales had a stronger correlation (r= 0.88) with physician ranking of scenarios than trade-off methods (r = 0.31). All methods were feasible and demonstrated good reliability, while rating scale method showed better construct validity than trade-off techniques. Conclusion. Relative to their current health, RA patients assigned low preference values to many glucocorticoid adverse events, particularly those associated with chronic fracture outcomes. Results varied with the preference measure used, indicating that methodological attributes of preference determinations must be considered in clinical decision making.

The association of race/ethnicity with the receipt of traditional and alternative arthritis-specific health care.

Background. The role of race/ethnicity in the receipt of arthritis-specific health care has not been well defined. Objective. To examine the association of race/ethnicity with the utilization of arthritis health care among community-dwelling older adults. Research Design. We used a computer-assisted telephone interview. Subjects. A population-based random sample was drawn from 6 preselected Alabama counties. Eligible respondents had self-reported arthritis and were over 50 years of age; 1424 people responded to the survey. Measures. Logistic regression was used to examine the association of race/ethnicity with the use of conventional (including use of a rheumatologist, primary care physician, and prescription arthritis medicines) and complementary and alternative medicines (CAM), including the use of chiropractic care, glucosamine and/or chondroitin, and herbals. Results. Reflecting stratified sampling, respondents were white (n = 852, 60%) or black (n = 528, 37%), female (72%), and had a mean age of 65 years. After multivariable adjustment, race/ethnicity was not a significant determinant of receiving rheumatology care or prescription arthritis medicines. However, whites were more likely than blacks to have seen a primary care physician for arthritis care (adjusted odds ratio [OR], 1.49; 95% confidence interval [CI], 1.12–1.98) or to have used CAM (OR, 1.47; 95% CI, 1.13–1.91) and twice as likely to have used glucosamine and/or chondroitin (OR, 1.99; 95% CI, 1.30–3.05). Conclusion. In this population of community-dwelling older adults, white race was significantly associated with CAM use and visits to primary care physicians for arthritis care. In contrast, the use of specialists and prescription arthritis medications was better explained by factors other than race/ethnicity, which included female gender, urban residence, higher educational level, and other arthritis-specific variables.

Improving the efficiency and effectiveness of pragmatic clinical trials in older adults in the United States

Pragmatic clinical trials (PCTs) seek to improve the generalizability and increase the statistical power of traditional explanatory trials. They are a major tenet of comparative effectiveness research. While a powerful study design, PCTs have been limited by high cost, modest efficiency, and limited ability to fill relevant evidence gaps. Based on an American Reinvestment and Recovery Act (ARRA) supported meeting of national stakeholders, we propose several innovations and future research that could improve the efficiency and effectiveness of such studies focused in the U.S. Innovations discussed include optimizing the use of community based practices through partnership with Practice Based Research Networks (PBRNs), using information technology to simplify PCT subject recruitment, consent and randomization processes, and utilizing linkages to large administrative databases, such as Medicare, as a mechanism to capture outcomes and other important PCT variables with lower subject and research team burden. Testing and adaptation of such innovations to PCT are anticipated to improve the public health value of these increasingly important studies.

Health-related quality of life among self-reported arthritis sufferers: Effects of race/ethnicity and residence

Objective: We evaluated differences in health-related quality of life (HRQoL) for African Americans and Caucasians with self-reported arthritis residing in rural and urban areas of a southern state. Methods: 1,191 individuals completed a telephone survey, which included the 12-Item Short Form Health Survey (SF-12). Participants were stratified into groups: African American/rural, Caucasian/rural, African American/urban, and Caucasian/urban. We evaluated differences and associations in HRQoL for the four groups.Results: Multivariable linear regression models revealed that being an African American rural resident was associated with worse self-reported mental health on the SF-12 even after adjusting for multiple confounding variables. In contrast, multivariable linear regression models revealed that being a Caucasian rural resident was associated with worse physical health SF-12 scores.Conclusions: The study revealed differences in HRQoL on the mental and physical health functioning scales of the SF-12 for African American rural and Caucasian rural residents. Researchers assessing HRQoL in arthritis patients should consider using a race/residence product term in their analyses.