John T. Schousboe

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.

2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis.

To develop a new evidence‐based, pharmacologic treatment guideline for rheumatoid arthritis (RA).

Personalizing Mammography by Breast Density and Other Risk Factors for Breast Cancer: Analysis of Health Benefits and Cost-Effectiveness

BACKGROUND Current guidelines recommend mammography every 1 or 2 years starting at age 40 or 50 years, regardless of individual risk for breast cancer. OBJECTIVE To estimate the cost-effectiveness of mammography by age, breast density, history of breast biopsy, family history of breast cancer, and screening interval. DESIGN Markov microsimulation model. DATA SOURCES Surveillance, Epidemiology, and End Results program, Breast Cancer Surveillance Consortium, and the medical literature. TARGET POPULATION U.S. women aged 40 to 49, 50 to 59, 60 to 69, and 70 to 79 years with initial mammography at age 40 years and breast density of Breast Imaging Reporting and Data System (BI-RADS) categories 1 to 4. TIME HORIZON Lifetime. PERSPECTIVE National health payer. INTERVENTION Mammography annually, biennially, or every 3 to 4 years or no mammography. OUTCOME MEASURES Costs per quality-adjusted life-year (QALY) gained and number of women screened over 10 years to prevent 1 death from breast cancer. RESULTS OF BASE-CASE ANALYSIS Biennial mammography cost less than

2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis: ACR RA Treatment Recommendations

100,000 per QALY gained for women aged 40 to 79 years with BI-RADS category 3 or 4 breast density or aged 50 to 69 years with category 2 density; women aged 60 to 79 years with category 1 density and either a family history of breast cancer or a previous breast biopsy; and all women aged 40 to 79 years with both a family history of breast cancer and a previous breast biopsy, regardless of breast density. Biennial mammography cost less than

Executive Summary of the 2013 International Society for Clinical Densitometry Position Development Conference on Body Composition

50,000 per QALY gained for women aged 40 to 49 years with category 3 or 4 breast density and either a previous breast biopsy or a family history of breast cancer. Annual mammography was not cost-effective for any group, regardless of age or breast density. RESULTS OF SENSITIVITY ANALYSIS Mammography is expensive if the disutility of false-positive mammography results and the costs of detecting nonprogressive and nonlethal invasive cancer are considered. LIMITATION Results are not applicable to carriers of BRCA1 or BRCA2 mutations. CONCLUSION Mammography screening should be personalized on the basis of a womans age, breast density, history of breast biopsy, family history of breast cancer, and beliefs about the potential benefit and harms of screening. PRIMARY FUNDING SOURCE Eli Lilly, Da Costa Family Foundation for Research in Breast Cancer Prevention of the California Pacific Medical Center, and Breast Cancer Surveillance Consortium.

A Comparison of Prediction Models for Fractures in Older Women: Is More Better

To develop a new evidence‐based, pharmacologic treatment guideline for rheumatoid arthritis (RA).

Reliability and accuracy of vertebral fracture assessment with densitometry compared to radiography in clinical practice

There have been many scientific advances in measurement of fat and lean body mass as determined by dual-energy X-ray absorptiometry (DXA). The International Society for Clinical Densitometry (ISCD) convened a Position Development Conference (PDC) on the use of DXA for body composition measurement. Previously, no guidelines to the use of DXA for body composition existed. The recommendations pertain to clinically relevant issues regarding DXA indications of use, acquisition, analysis, quality control, interpretation, and reporting were addressed. The topics and questions for consideration were developed by the ISCD Board of Directors and the Scientific Advisory Committee and were designed to address the needs of clinical practitioners. Three Task Forces were created and assigned these questions and asked to conduct comprehensive literature reviews. The Task Forces included participants from 6 countries and a variety of interests including academic institutions, private clinics, and industry. Reports with proposed Position Statements were then presented to an international panel of experts with backgrounds in DXA and bone densitometry and a variety of fields that use body composition measures. The PDC was held in Tampa, FL, contemporaneously with the Annual Meeting of the ISCD, March 21 through March 23, 2013. This report describes the methodology of the 2013 ISCD Body Composition PDC and summarizes the results. Three separate articles in this issue will detail the rationale, discussion, and additional research topics for each question the Task Forces addressed.

Fracture Risk Prediction by Non-BMD DXA Measures: the 2015 ISCD Official Positions Part 2: Trabecular Bone Score.

BACKGROUND A Web-based risk assessment tool (FRAX) using clinical risk factors with and without femoral neck bone mineral density (BMD) has been incorporated into clinical guidelines regarding treatment to prevent fractures. However, it is uncertain whether prediction with FRAX models is superior to that based on parsimonious models. METHODS We conducted a prospective cohort study in 6252 women 65 years or older to compare the value of FRAX models that include BMD with that of parsimonious models based on age and BMD alone for prediction of fractures. We also compared FRAX models without BMD with simple models based on age and fracture history alone. Fractures (hip, major osteoporotic [hip, clinical vertebral, wrist, or humerus], and any clinical fracture) were ascertained during 10 years of follow-up. Area under the curve (AUC) statistics from receiver operating characteristic curve analysis were compared between FRAX models and simple models. RESULTS The AUC comparisons showed no differences between FRAX models with BMD and simple models with age and BMD alone in discriminating hip (AUC, 0.75 for the FRAX model and 0.76 for the simple model; P = .26), major osteoporotic (AUC, 0.68 for the FRAX model and 0.69 for the simple model; P = .51), and clinical fracture (AUC, 0.64 for the FRAX model and 0.63 for the simple model; P = .16). Similarly, performance of parsimonious models containing age and fracture history alone was nearly identical to that of FRAX models without BMD. The proportion of women in each quartile of predicted risk who actually experienced a fracture outcome did not differ between FRAX and simple models (P > or = .16). CONCLUSION Simple models based on age and BMD alone or age and fracture history alone predicted 10-year risk of hip, major osteoporotic, and clinical fracture as well as more complex FRAX models.

The American Academy of Orthopaedic Surgeons evidence-based guideline on: treatment of osteoarthritis of the knee, 2nd edition.

Absorptiometry of the thoraco-lumbar spine at the time of bone densitometry to detect vertebral deformities consistent with fracture is now available. The performance of absorptiometry in clinical practice compared to radiography has not been fully established, especially in the presence of osteoarthritis or scoliosis. Our first objective was to compare absorptiometry to radiography for detection of vertebral deformity in elderly women who were referred for bone densitometry with or without scoliosis or disc space osteoarthritis excluded. Our second objective was to assess the effect of osteoarthritis and scoliosis on the inter-rater reliability of both technologies. The study group comprised two hundred five women age 65 and older referred for bone densitometry in a large multispecialty group practice. Lateral and antero-posterior (AP) absorptiometry images and lateral spine radiographs were obtained on all participants. The vertebrae on all images were evaluated for vertebral deformity by two observers according to the Genant semiquantitative criteria who were blinded to each other’s readings. Disc spaces were evaluated on radiographs for osteoarthritis. Absorptiometry AP images were evaluated for scoliosis. In the absence of scoliosis, the sensitivity and specificity of absorptiometry for persons with one or more radiographic grade 2–3 deformities (>25% reduction of vertebral height) for the two readers were 87–93% and 93–95%, respectively. The inter-rater reliability of absorptiometry improved in the absence of moderate or severe disc space osteoarthritis. A strategy of absorptiometry with follow-up radiography only in those with scoliosis or apparent grade 2 deformity accurately identifies those with prevalent grade 2 or 3 deformity on radiography (accuracy 0.98 and kappa 0.86 for reader 1; accuracy 0.99 and kappa 0.92 for reader 2). Lateral and AP absorptiometry imaging of the spine with selective follow-up radiography accurately identifies elderly women with vertebral deformity consistent with moderate or severe fracture, but extra caution is necessary when evaluating vertebrae in the presence of adjacent disc space osteoarthritis.

Universal bone densitometry screening combined with alendronate therapy for those diagnosed with osteoporosis is highly cost-effective for elderly women

Bone mineral density (BMD) as measured by dual-energy X-ray absorptiometry (DXA) is the gold standard for the diagnosis and management of osteoporosis. However, BMD explains only 60%-80% of bone strength, and a number of skeletal features other than BMD contribute to bone strength and fracture risk. Advanced imaging modalities can assess some of these skeletal features, but compared to standard DXA, these techniques have higher costs and limited accessibility. A major challenge, therefore, has been to incorporate in clinical practice a readily available, noninvasive technology that permits improvement in fracture-risk prediction beyond that provided by the combination of standard DXA measurements and clinical risk factors. To this end, trabecular bone score (TBS), a gray-level textural index derived from the lumbar spine DXA image, has been investigated. The purpose of this International Society for Clinical Densitometry task force was to review the evidence and develop recommendations on how to incorporate TBS in clinical practice. Clinical applications of TBS for fracture risk assessment, treatment initiation, monitoring of treatment, and use of TBS in special conditions related to greater fracture risk, were addressed. We present the official positions approved by an expert panel following careful review of the recommendations and evidence presented by the TBS task force.