Aseem Bharat

Bio: Aseem Bharat is an academic researcher from University of Alabama at Birmingham. The author has contributed to research in topics: Health care & Clinical trial. The author has an hindex of 9, co-authored 14 publications receiving 1637 citations. Previous affiliations of Aseem Bharat include Veterans Health Administration & University of Alabama.

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

Abstract: 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.

Linkage of a De‐Identified United States Rheumatoid Arthritis Registry With Administrative Data to Facilitate Comparative Effectiveness Research

Abstract: Objective Linkages between registries and administrative data may provide a valuable resource for comparative effectiveness research. However, personal identifiers that uniquely identify individuals are not always available. Here we describe methods to link a de-identified arthritis registry and US Medicare data. The linked data set was also used to evaluate the generalizability of the registry to the US Medicare population. Methods Rheumatoid arthritis (RA) patients participating in the Consortium of Rheumatology Researchers of North America (CORRONA) registry were linked to Medicare data restricted to rheumatology claims or claims for RA. Deterministic linkage was performed using age, sex, provider identification number, and geographic location of the CORRONA site. We then searched for visit dates in Medicare matching visit dates in CORRONA, requiring ≥1 exact matching date. Linkage accuracy was quantified as a positive predictive value in a subcohort (n = 1,581) with more precise identifiers. Results CORRONA participants with self-reported Medicare (n = 11,001) were initially matched to 30,943 Medicare beneficiaries treated by CORRONA physicians. A total of 8,431 CORRONA participants matched on ≥1 visit; 5,317 matched uniquely on all visits. The number of patients who linked and linkage accuracy (from the subcohort) were high for patients with >2 visits (n = 3,458, 98% accuracy), exactly 2 visits (n = 822, 96% accuracy), and 1 visit (n = 1,037, 79% accuracy) that matched exactly on calendar date. Demographics and comorbidity profiles of registry participants were similar to nonparticipants, except participants were more likely to take disease-modifying antirheumatic drugs and biologic agents. Conclusion Linkage between a national, de-identified outpatient arthritis registry and Medicare data on multiple nonunique identifiers appears feasible and valid.

Incidence and Risk Factors for Progressive Multifocal Leukoencephalopathy among Patients with Selected Rheumatic Diseases

Abstract: Objective To ascertain the incidence of progressive multifocal leukoencephalopathy (PML) in patients with selected rheumatic diseases, to describe the characteristics of PML cases occurring in this setting, and to evaluate the extent to which such cases occurred in the context of biologic therapies such as rituximab or tumor necrosis factor antagonists. Methods We conducted a large population-based study to describe the incidence and risk factors for PML among patients with rheumatoid arthritis, psoriatic arthritis, psoriasis, juvenile idiopathic arthritis, inflammatory bowel disease, and ankylosing spondylitis using national inpatient and outpatient administrative data from the entire Center for Medicare and Medicaid Services from 2000–2009. Suspected PML cases were identified using hospital discharge diagnosis codes. Risk factors for PML were evaluated using outpatient data ≥6 months prior to PML diagnosis. Results Among 2,030,578 patients with autoimmune diseases of interest, a total of 53 PML cases were identified (2.6 per 100,000 patients). Most PML cases had human immunodeficiency virus (HIV) and/or cancer. Nine PML cases had evidence for biologic use prior to PML hospitalization, of which 3 had neither HIV nor malignancy and were exposed to biologics within 12 (rituximab) or 6 months (all other biologics) prior to PML diagnosis. PML occurred at an estimated incidence of 0.2 per 100,000 patients with autoimmune diseases who did not have HIV or malignancy. Conclusion PML occurs at a very low incidence among patients with rheumatic diseases but can occur even in the absence of HIV or malignancy.

Patient’s experience with subcutaneous and oral methotrexate for the treatment of rheumatoid arthritis

Abstract: Despite the prominent position of methotrexate (MTX) in Rheumatoid Arthiris (RA) therapeutics, its real-world effectiveness may be influenced by a relative lack of tolerability or other side effects that physicians may not be aware of but that are bothersome to patients. The aim of this study is to identify suboptimal patient experience with MTX and to raise awareness for clinicians to identify opportunities to mitigate bothersome symptoms and side effects and optimize response to MTX. We conducted a prospective, cross-sectional, online survey among RA patients who were members of Creakyjoints, a large arthritis patient community. Eligible participants must have recently initiated a new biologic, subcutaneous (SQ) MTX, or oral MTX in the last 12 months and were uniquely assigned to one of these 3 groups. Descriptive statistics were used to compare patient-reported side effects and tolerability related to MTX use in the 3 medication groups (SQ MTX, oral MTX, and biologic). A total of 382 (85 %) of 448 eligible patients completed the survey and were grouped as: biologic (n = 218), SQ MTX (n = 49), and oral MTX (n = 115). Demographics were mean standard deviation (SD) age 48 (10) years, 92 % white, 91 % women. Symptoms significantly more prevalent in the SQ and oral MTX groups included diarrhea, fatigue, malaise, and hair loss. Injection related pain was lower with SQ MTX compared to SQ biologics. Out of a total of 8 potential symptoms and side effects examined, higher dose MTX (> = 20 mg/week) was associated with a 2.26 (1.25–4.09) greater likelihood of more side effects referent to < =10 mg/week. Results from this real-world RA patient cohort suggest that MTX is accompanied by many patient-reported side effects and tolerability problems that may be under-recognized by physicians. These may impact both treatment satisfaction and medication adherence.

Physicians' explanations for apparent gaps in the quality of rheumatology care: Results from the US Medicare Physician Quality Reporting System

Abstract: Objective The metrics used to assess quality of care and pay for performance in rheumatology are increasingly important. The Centers for Medicare and Medicaid Services established the Physician Quality Reporting System (PQRS) to allow physicians to report performance measures for many conditions, including osteoporosis and rheumatoid arthritis (RA). We described the frequency and nature of physician-reported reasons why recommended care for individual osteoporosis and RA patients was not provided. Methods Using national data on Medicare fee-for-service beneficiaries (2007–2009), we identified health care providers reporting on quality of care for any of 3 osteoporosis or 3 RA measures. PQRS reason codes allowed physicians to submit explanations why recommended care was not given. Results In 2009, 1,775 physicians reported on ≥1 osteoporosis PQRS measure and 630 physicians reported on ≥1 RA measure. For the older women whose physician reported on lifetime dual x-ray absorptiometry screening at least once since the age of 60 years via PQRS, 76% received such screening. Among the patients with physician-diagnosed osteoporosis reported via PQRS, 82% received prescription osteoporosis medication in the preceding year. For RA medication use reported via PQRS, 89% of patients received a disease-modifying antirheumatic drug or a biologic agent. For the remaining 11–24% of osteoporosis and RA patients, physicians reported medical, patient, system, or other reasons why care was considered but not provided. Conclusion A substantial fraction of Medicare enrollees who did not receive recommended osteoporosis or RA care had physician-documented reasons for why care was not provided. For Medicare and other health plans that implement penalties for apparent nonperformance or delivery of suboptimal care, it will be important to allow physicians to provide reasons that care was considered medically inappropriate, refused, or otherwise not feasible.

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update

Abstract: In this article, the 2010 European League against Rheumatism (EULAR) recommendations for the management of rheumatoid arthritis (RA) with synthetic and biological disease-modifying antirheumatic drugs (sDMARDs and bDMARDs, respectively) have been updated. The 2013 update has been developed by an international task force, which based its decisions mostly on evidence from three systematic literature reviews (one each on sDMARDs, including glucocorticoids, bDMARDs and safety aspects of DMARD therapy); treatment strategies were also covered by the searches. The evidence presented was discussed and summarised by the experts in the course of a consensus finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) were determined. Fourteen recommendations were developed (instead of 15 in 2010). Some of the 2010 recommendations were deleted, and others were amended or split. The recommendations cover general aspects, such as attainment of remission or low disease activity using a treat-to-target approach, and the need for shared decision-making between rheumatologists and patients. The more specific items relate to starting DMARD therapy using a conventional sDMARD (csDMARD) strategy in combination with glucocorticoids, followed by the addition of a bDMARD or another csDMARD strategy (after stratification by presence or absence of adverse risk factors) if the treatment target is not reached within 6 months (or improvement not seen at

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

Abstract: Objective To develop a new evidence-based, pharmacologic treatment guideline for rheumatoid arthritis (RA). Methods We conducted systematic reviews to synthesize the evidence for the benefits and harms of various treatment options. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence. We employed a group consensus process to grade the strength of recommendations (either strong or conditional). A strong recommendation indicates that clinicians are certain that the benefits of an intervention far outweigh the harms (or vice versa). A conditional recommendation denotes uncertainty over the balance of benefits and harms and/or more significant variability in patient values and preferences. Results The guideline covers the use of traditional disease-modifying antirheumatic drugs (DMARDs), biologic agents, tofacitinib, and glucocorticoids in early (<6 months) and established (≥6 months) RA. In addition, it provides recommendations on using a treat-to-target approach, tapering and discontinuing medications, and the use of biologic agents and DMARDs in patients with hepatitis, congestive heart failure, malignancy, and serious infections. The guideline addresses the use of vaccines in patients starting/receiving DMARDs or biologic agents, screening for tuberculosis in patients starting/receiving biologic agents or tofacitinib, and laboratory monitoring for traditional DMARDs. The guideline includes 74 recommendations: 23% are strong and 77% are conditional. Conclusion This RA guideline should serve as a tool for clinicians and patients (our two target audiences) for pharmacologic treatment decisions in commonly encountered clinical situations. These recommendations are not prescriptive, and the treatment decisions should be made by physicians and patients through a shared decision-making process taking into account patients’ values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.

Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis

Abstract: Rheumatoid arthritis (RA) is a prevalent systemic autoimmune disease, caused by a combination of genetic and environmental factors. Animal models suggest a role for intestinal bacteria in supporting the systemic immune response required for joint inflammation. Here we performed 16S sequencing on 114 stool samples from rheumatoid arthritis patients and controls, and shotgun sequencing on a subset of 44 such samples. We identified the presence of Prevotella copri as strongly correlated with disease in new-onset untreated rheumatoid arthritis (NORA) patients. Increases in Prevotella abundance correlated with a reduction in Bacteroides and a loss of reportedly beneficial microbes in NORA subjects. We also identified unique Prevotella genes that correlated with disease. Further, colonization of mice revealed the ability of P. copri to dominate the intestinal microbiota and resulted in an increased sensitivity to chemically induced colitis. This work identifies a potential role for P. copri in the pathogenesis of RA.

2012 American College of Rheumatology guidelines for management of gout. Part 1: Systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia

Abstract: DINESH KHANNA, JOHN D. FITZGERALD, PUJA P. KHANNA, SANGMEE BAE, MANJIT K. SINGH, TUHINA NEOGI, MICHAEL H. PILLINGER, JOAN MERILL, SUSAN LEE, SHRADDHA PRAKASH, MARIAN KALDAS, MANEESH GOGIA, FERNANDO PEREZ-RUIZ, WILL TAYLOR, FREDERIC LIOTE, HYON CHOI, JASVINDER A. SINGH, NICOLA DALBETH, SANFORD KAPLAN, VANDANA NIYYAR, DANIELLE JONES, STEVEN A. YAROWS, BLAKE ROESSLER, GAIL KERR, CHARLES KING, GERALD LEVY, DANIEL E. FURST, N. LAWRENCE EDWARDS, BRIAN MANDELL, H. RALPH SCHUMACHER, MARK ROBBINS, NEIL WENGER, AND ROBERT TERKELTAUB

American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis

Abstract: In the United States, approximately 35% of adults with Systemic Lupus Erythematosus (SLE) have clinical evidence of nephritis at the time of diagnosis; with an estimated total of 50–60% developing nephritis during the first 10 years of disease [1–4]. The prevalence of nephritis is significantly higher in African Americans and Hispanics than in Caucasians, and is higher in men than in women. Renal damage is more likely to develop in non-Caucasian groups [2–4]. Overall survival in patients with SLE is approximately 95% at 5 years after diagnosis and 92% at 10 years [5, 6]. The presence of lupus nephritis significantly reduces survival, to approximately 88% at 10 years, with even lower survival in African Americans [5, 6]. The American College of Rheumatology (ACR) last published guidelines for management of systemic lupus erythematosus (SLE) in 1999 [7]. That publication was designed primarily for education of primary care physicians and recommended therapeutic and management approaches for many manifestations of SLE. Recommendations for management of lupus nephritis (LN) consisted of pulse glucocorticoids followed by high dose daily glucocorticoids in addition to an immunosuppressive medication, with cyclophosphamide viewed as the most effective immunosuppressive medication for diffuse proliferative glomerulonephritis. Mycophenolate mofetil was not yet in use for lupus nephritis and was not mentioned. Since that time, many clinical trials of glucocorticoids-plus-immunosuppressive interventions have been published, some of which are high quality prospective trials, and some not only prospective but also randomized. Thus, the ACR determined that a new set of management recommendations was in order. A combination of extensive literature review and the opinions of highly qualified experts, including rheumatologists, nephrologists and pathologists, has been used to reach the recommendations. The management strategies discussed here apply to lupus nephritis in adults, particularly to those receiving care in the United States of America, and include interventions that were available in the United States as of April 2011. While these recommendations were developed using rigorous methodology, guidelines do have inherent limitations in informing individual patient care; hence the selection of the term “recommendations.” While they should not supplant clinical judgment or limit clinical judgment, they do provide expert advice to the practicing physician managing patients with lupus nephritis.