Association Between Payments by Pharmaceutical Manufacturers and Prescribing Behavior in Rheumatology.

OBJECTIVE: To evaluate the association between pharmaceutical industry payments to rheumatologists and their prescribing behaviors. METHODS: A cross-sectional analysis was conducted of Medicare Part B Public Use File, Medicare Part D Public Use File, and Open Payments data for 2013 to 2015. Prescription drugs responsible for 80% of the total Medicare pharmaceutical expenditures in rheumatology were analyzed. We calculated the mean annual drug cost per beneficiary per year, the percentage of rheumatologists who received payments, and the median annual payment per physician per drug per year. Industry payments were categorized as food/beverage and consulting/compensation. Multivariable regression models were used to assess associations between industry payments and both prescribing patterns and prescription drug expenditures. RESULTS: Of 4822 rheumatologists in the Medicare prescribing databases, 3729 received any payment from a pharmaceutical company during this time frame. Food/beverage payments were associated with an increased proportion of prescriptions for the related drugs (range, 1.5% to 4.5%) and an increased proportion of annual Medicare spending for the related drugs (range, 3% to 23%). For every $100 in food/beverage payments, the probability of prescribing increased (range, 1.5% to 14% for most drugs) and Medicare reimbursements increased (range, 6% to 44% for most drugs). Consulting/compensation payments were associated with an increased proportion of prescriptions (range, 1.2% to 1.6%) and an increased proportion of annual Medicare spending (range, 1% to 2%). For every $1000 in consulting/compensation payments, both the probability of prescribing increased (5% or less for most drugs) and Medicare reimbursements increased (less than 10% for most drugs). CONCLUSION: Payments to rheumatologists by pharmaceutical companies are associated with increased probability of prescribing and Medicare spending.

Definition and construct validation of clinically relevant cutoffs on the Flare Assessment in Rheumatoid Arthritis (FLARE-RA) questionnaire.

OBJECTIVE: The Flare Assessment in Rheumatoid Arthritis (FLARE-RA) questionnaire was devised for the detection of flares in patients with RA. We aimed to define construct validity and cut-off(s) for the FLARE-RA questionnaire. METHODS: This cross-sectional study included adult patients with prevalent RA (2010 ACR/EULAR criteria) attending outpatient rheumatology clinics in France (n = 138), Denmark (n = 253), USA (n = 75), and Argentina (n = 105). Flare occurrence over the past 3 months was assessed with the FLARE-RA questionnaire scoring from 0 (no flare) to 10 (maximum flare). The cut-offs for the FLARE-RA score were defined using the following anchor items obtained at the same encounter: (1) Patient report of flare; (2) DAS28-CRP > 3.2; (3) Change of anti-rheumatic treatment, based on the area under the receiver operating characteristic curve (AUC) and distance to (0,1). RESULTS: Four hundred seventy four patients with RA duration ≥2 years (mean age 58.6 years, 74.9% female) were included in the main analysis. The discrimination for the FLARE-RA cut-offs was acceptable-to-excellent: AUC for the global FLARE-RA score ranged from 0.71 to 0.92. The cut-offs for the FLARE-RA score were lower using "patient report of flare" than DAS28-CRP and "change of anti-rheumatic treatment". Proposed FLARE-RA cut-offs for clinical detection and change of anti-rheumatic treatment are 2 and 5, respectively, for patients with RA duration 2-5 years, and 2 and 3.5, respectively, for patients with RA duration >5 years. CONCLUSIONS: Proposed FLARE-RA cut-offs have acceptable discriminative capacity across the tested anchor items and are expected to aid in early recognition and timely management of RA flares.

Treatments for giant cell arteritis: Meta-analysis and assessment of estimates reliability using the fragility index.

BACKGROUND: To better communicate the results of randomized controlled trials (RCTs) of giant cell arteritis (GCA), we propose the use of the fragility index (FI), which is an intuitive measure defined as the minimum number of subjects whose status would have to change (e.g., from having the outcome to not) to render a statistically significant result nonsignificant, or vice-versa. METHODS: We conducted a systematic review and random-effects meta-analysis of RCTs of glucocorticoid (GC) sparing strategies for relapse-free maintenance in GCA, and used the FI to simplify the presentation of results. RESULTS: Ten RCTs (nine phase II and one phase III enrolling 645 subjects) were included. Tocilizumab, IV GC and methotrexate significantly improved the likelihood of being relapse free with relative risks and 95% confidence intervals of 3.54 (2.28, 5.51), 5.11 (1.39, 18.81) and 1.54 (1.02, 2.30); respectively. The median FI was 4.5 (range, 1-28), and was generally higher for negative RCTs (n = 6; median FI 4.5) than for positive RCTs (n = 4; median FI 3.5). The range of FI per treatment was (1-8) for methotrexate, (2-6) for anti-TNF agents, 4 for abatacept, 3 for IV GC pulses and (4-28) for tocilizumab. CONCLUSION: Tocilizumab, IV GC and methotrexate improve the likelihood of being relapse-free in subjects with GCA. Assessment of GC sparing strategies in GCA has long depended on imprecise trials that would change significance if outcomes were reversed for a handful of subjects. FI may be used in rheumatology to simplify communication of statistical significance and overcome limitations of p-value.

Assessment of the frequency of cardiovascular risk factors in patients with Takayasu's arteritis.

Objectives: The prevalence of atherosclerotic risk factors and disease in Takayasu's arteritis (TAK) has not been well defined. We aimed to assess the frequency of cardiovascular (CV) risk factors and the incidence of CV events (CVEs) in patients with TAK from two ethnically different populations. Methods: Patients with TAK followed at Mayo Clinic, Rochester, MN, USA and Marmara University, Istanbul, Turkey were included in this retrospective study. Patients with TAK were compared with age-, sex- and calendar year-matched controls from the same geographical region without TAK. The 2008 Framingham 10-year general CV risk score (FRS) was used for the evaluation of CV risk at the time of TAK incidence/index date. Results: In total, 191 patients with TAK and 191 non-TAK controls were included. Hypertension and the prevalence of lipid-lowering treatments were significantly more frequent in TAK. Prior to the incidence/index date, occurrence of CVE was significantly higher in TAK. The FRS was significantly higher in TAK compared with non-TAK at incidence/index date. The cumulative incidence of CVE was 15.4% at 10 years in TAK vs 5.8% in non-TAK; the risk of CVE was increased among patients with TAK (hazard ratio = 4.36; 95% CI: 1.25, 15.13). Conclusion: CV risk factors are more common in patients with TAK, particularly hypertension. The FRS is higher in patients with TAK at the time of diagnosis. The cumulative incidence of CVE was also significantly higher during follow-up in TAK. Our results suggest that patients with TAK should undergo careful assessment of CV risk factors, and an aggressive risk modification approach is warranted.

Healthcare Use and Direct Cost of Giant Cell Arteritis: A Population-based Study.

OBJECTIVE: To determine the healthcare use and direct medical cost of giant cell arteritis (GCA) in a population-based cohort. METHODS: A well-defined, retrospective population-based cohort of Olmsted County, Minnesota, USA, residents diagnosed with GCA from 1982-2009 was compared to a matched referent cohort from the same population. Standardized cost data (inflation-adjusted to 2014 US dollars) for 1987-2014 and outpatient use data for 1995-2014 were obtained. Use and costs were compared between cohorts through signed-rank paired tests, McNemar's tests, and quantile regression models. RESULTS: Significant annual differences in outpatient costs were observed for patients with GCA in each of the first 4 years (median differences: $2085, $437, $382, $388, respectively). In adjusted analyses, median incremental cost attributed to GCA over a 5-year period was $4662. Compared with matched referent subjects, patients with GCA had higher use of laboratory visit-days annually for each of the first 3 years following incidence/index date, and increased outpatient physician visits for years 0-1, 1-2, and 3-4. Patients with GCA had significantly more radiology visit-days in years 0-1, 3-4, and 4-5, and more ophthalmologic procedures/surgery in years 0-1, 1-2, 2-3, and 4-5 compared to non-GCA. Emergency medicine visits, musculoskeletal, and cardiovascular procedures/surgery were similar between GCA and non-GCA groups throughout the study period. CONCLUSION: Direct medical outpatient costs were increased in the month preceding and in the first 4 years following GCA diagnosis. Higher use of outpatient physician, laboratory, and radiology visits, and ophthalmologic procedures among these patients accounts for the increased cost of care.

Malignancy Incidence, Management, and Prevention in Patients with Rheumatoid Arthritis.

Traditional and biologic disease-modifying antirheumatic drugs (DMARDs) are effective medications for the management of rheumatoid arthritis (RA). However, the effects of these medications on immune function raises concern that they may increase long-term cancer risk. The baseline risk for some cancers appears to differ in patients with RA compared to the general population, with the former having an increased risk of lymphoma, lung cancer and renal cancer, but a decreased risk of colorectal and breast cancer. Some DMARDs appear to increase the rate of specific cancer types (such as bladder cancer with cyclophosphamide), but few appear to increase the overall cancer risk. Studying the link between lymphoma and disease severity in RA is complicated because patients with persistently active disease are at increased risk for lymphoma, and disease severity correlates with more intense use of immunosuppressive medications. Overall, cancer risk in patients with RA is slightly above that of the general population, with the increased risk likely secondary to an increased risk of lymphomas in those with high disease activity. Risk mitigation includes management of RA disease activity as well as age- and sex-appropriate cancer screening.

Cardiovascular risk assessment in patients with rheumatoid arthritis: a correlative study of noninvasive arterial health testing.

This study aimed to determine the relationship between noninvasive measures of arterial health and both estimated 10-year cardiovascular risk and measures of disease activity over time in established rheumatoid arthritis. Fifty rheumatoid arthritis patients underwent noninvasive arterial health testing (brachial artery reactivity, aortic augmentation index [AIx], pulse wave velocity, carotid artery intima-media thickness, and carotid artery plaque presence) and assessment of clinical disease activity (tender or swollen joint counts, Clinical Disease Activity Index [CDAI], and Health Assessment Questionnaire II [HAQ-II]). Clinical measures during 3 years before the study visit were averaged. Arterial health testing was compared with the American Heart Association/American College of Cardiology (AHA/ACC) Pooled Cohort Equation. Spearman methods identified correlations between disease activity measures, cardiac biomarkers, and arterial health parameters. Among the patients (mean age, 57.5 years), disease activity was moderate (mean [SD] CDAI, 16.9 [15.3]). At the study visit, corrected aortic augmentation index correlated with CDAI (r = 0.37, P = .009) and HAQ-II (r = 0.33, P = .02). AIx correlated with time-averaged tender joint count (r = 0.37, P = .008), CDAI (r = 0.36, P = .01), HAQ-II (r = 0.36, P = .01), swollen joint count (r = 0.36, P = .10), patient global assessment (r = 0.33, P = .02), physician global assessment (r = 0.35, P = .01), and pain score (r = 0.38, P = .007). The AHA/ACC low-risk group (<5% 10-year risk) had highest prevalence of carotid plaques. Arterial health testing may identify increased risk of cardiovascular disease compared with risk obtained through AHA/ACC Pooled Cohort Equation. Measures of arterial stiffness correlate with the burden of disease activity over time.

Rheumatology Workforce Planning in Western Countries: A Systematic Literature Review.

OBJECTIVE: To compare health care planning models forecasting rheumatology workforce requirements in western countries. METHODS: A systematic literature review was conducted through medical databases (Ovid MEDLINE, Embase, CINAHL, and Cochrane Library) and the grey literature. All articles reporting a rheumatology workforce model were included. RESULTS: The search yielded 6,508 articles, and 14 publications (on 12 studies) were included. Workforce models were available for the US (n = 3), Canada (n = 3), the US plus Canada (n = 1), Germany (n = 2), Spain (n = 1), and the UK (n = 2). The number of rheumatologists required to serve a population of 100,000 people was calculated, with a range of 0.7 (UK, calculated for 1988) to 3.5 (Spain, calculated for 2021). Most models used a needs-based approach (n = 6); 3 studies each applied a supply- or demand-based method. The following variables were considered by ≥1 model: disease prevalence, patients' referral to rheumatologists, clinical visits/patient/year, population development, factors influencing performance of rheumatologists, patient flow/care sharing, and medical technologies/infrastructure development. CONCLUSION: Heterogeneity in methods used, the period or calendar years for which the estimates were projected, and heterogeneity of variables evaluated led to disparate estimates, with results ranging from 0.7 to 3.5 rheumatologists per 100,000 population. An international initiative is needed to agree upon a common approach for a reliable estimation of manpower requirements in rheumatology.

Frequency of radiologic procedures in patients with rheumatoid arthritis.

BACKGROUND: Patients with rheumatoid arthritis (RA) undergo radiologic investigations for disease and comorbidity evaluation. The actual use of radiologic imaging in RA is unknown. METHODS: Using the Rochester Epidemiology Project medical record linkage system, adult patients from previously assembled population-based cohorts of Olmsted County, Minnesota, residents who fulfilled the 1987 American College of Rheumatology criteria for RA in 1988 to 2007 and comparator subjects without RA of similar age and gender were studied. Data on all radiologic procedures performed were collected. RESULTS: The study included 650 patients with RA and 650 patients without RA. Patients with RA had significantly more radiographs of the chest (rate ratio [RR], 1.33; 95% confidence interval [CI], 1.28-31.38), upper extremity (RR, 2.97; 95% CI, 2.80-83.17), lower extremity (RR, 2.05; 95% CI, 1.94-102.16), spine (RR, 1.46; 95% CI, 1.35-41.59), and hip, pelvis, or sacroiliac joints (RR, 1.14; 95% CI, 1.03-11.26), as well as bone radionuclide (RR, 1.90; 95% CI, 1.50-52.44) and dual-energy x-ray absorptiometry imaging (RR, 1.77; 95% CI, 1.59-61.98) compared with patients without RA. Among patients with RA, having a positive rheumatoid factor was associated with an increased likelihood of undergoing radiologic procedures (RR, 1.05; 95% CI, 1.02-11.07). Women with RA underwent more imaging procedures than men (RR, 1.20; 95% CI, 1.16-21.23). CONCLUSIONS: Patients with RA undergo more radiologic procedures than patients without RA. Among patients with RA, women and patients with a positive rheumatoid factor have more radiologic procedures. The utilization of radiography is likely a reflection of overall disease burden. Despite some guidelines, routine hand wrist radiographs were not obtained with regularity; "overuse" is unlikely.

Cardiovascular disease assessment in rheumatoid arthritis: a guide to translating knowledge of cardiovascular risk into clinical practice.

As physicians we like to have evidence for making decisions about interventions to improve health. The evidence vacuum in the field of cardiovascular disease (CVD) prevention and clinical outcome in patients with rheumatoid arthritis (RA) has received vigorous attention in the recent literature. There is broad agreement that a patient with RA fulfilling the criteria established for the general population on CVD risk reduction should receive proven interventions, including smoking cessation, weight reduction, blood pressure control and lipid-lowering therapy. In accordance with these recommendations, and despite all the uncertainties about CVD treatment threshold, targets and outcome results in RA, we firmly advocate that CVD risk should be assessed and acted on in patients with RA as recommended for the general population, even while educational CVD-preventive programmes are being developed and hard CVD end point studies are undertaken in this patient population. The initial strategies for implementing CVD risk evaluation will necessarily be modest at first. There are several possible strategies for collection of data that can be incorporated into the daily routine during rheumatology consultations at outpatient clinics. We recommend starting with these simple procedures: 1. CVD risk factor recording and evaluation using risk calculators available for the general population 2. Referral of patients with high CVD risk to a primary care physician or a cardiologist skilled in this subject for follow-up 3. Providing information about excess CVD risk and how to modify it to the patients as major stakeholders.

Cardiovascular risk in psoriasis: a population-based analysis with assessment of the framingham risk score.

Objective. To examine the utility of the Framingham risk score (FRS) in estimating cardiovascular risk in psoriasis. Methods. We compared the predicted 10-year risk of cardiovascular events, namely, cardiovascular death, myocardial infarction, heart failure, percutaneous transluminal coronary angioplasty, and coronary artery bypass grafting using the FRS, to the observed risk of cardiovascular events in a population-based cohort of patients with psoriasis. Patients with incident or prevalent adult-onset psoriasis aged 30-79 years without prior history of cardiovascular disease were included. Results. Among the 1197 patients with predicted risk scores, the median FRS was 6.0%, while the observed 10-year cardiovascular risk was 6.9% (standardized incidence ratio (SIR): 1.14; 95% confidence interval (CI): 0.92-1.42). The SIR was not elevated for women nor for men. The differences between observed and predicted cardiovascular risks in patients <60 years (SIR: 1.01; 95% CI: 0.73-1.41) or ≥60 years (SIR: 1.26; 95% CI: 0.95-1.68) were not statistically significant. Conclusion. There was no apparent difference between observed and predicted cardiovascular risks in patients with psoriasis in our study. FRS reasonably estimated cardiovascular risk in both men and women as well as in younger and older psoriasis patients, suggesting that FRS can be used in risk stratification in psoriasis without further adjustment.

The future of damage assessment in vasculitis.

Damage denotes the aspects of chronic disease that do not reverse with therapy. This concept is particularly important for the primary systemic vasculitides, since the careful differentiation between activity and damage may help avoid unnecessary exposure to cytotoxic medications. Damage significantly influences both longterm prognosis and quality of life. Because the primary systemic vasculitides have diverse manifestations, the use of a damage assessment instrument is crucial to ensure reproducibility. The Vasculitis Damage Index (VDI) is the only validated measure for damage assessment in vasculitis. Use of the VDI in recent clinical trials has shown that it may not adequately determine the full spectrum of damage experienced by patients with vasculitis of small- and medium-size vessels. We propose reexamining the way in which damage is assessed, focusing on vasculitides of small- and medium-size vessels, and outline an initiative to create a substantially revised and improved damage assessment instrument using data-driven approaches. This initiative is part of a larger international effort to create a unified approach to disease assessment for the primary systemic vasculitides.

Primer: Demystifying risk--understanding and communicating medical risks.

Assessments of risk are a critical part of the practice of evidence-based medicine. Comprehension of various risk measures, such as absolute risk, relative risk, attributable risk, odds ratio, and hazard ratio, is essential to understand the medical literature, and to communicate health risks effectively. Complex risk measures, including number needed to treat and survival estimates that are adjusted for competing risks, are often misunderstood. Communication of these concepts to patients can be a challenge. The patient's perception of risk stems not only from the way risks are stated, but also from family history, personal experiences, cultural norms, and beliefs. A multifaceted approach to risk communication that uses both qualitative and quantitative assessments of risk, and addresses the timing and permanence of risks, is necessary to ensure the patient understands the potential risks. Successful communication involves interaction with the patient to understand the patient's perspective and to aid in personalized decision-making. In the face of uncertainty, making a provisional decision with a plan to review it later can be a good strategy. Verifying the patient's comprehension can help ensure that the decisions reached are informed and acceptable.

Morphologic and quantitative assessment of CD20+ B cell infiltrates in rheumatoid arthritis-associated nonspecific interstitial pneumonia and usual interstitial pneumonia.

OBJECTIVE: B lymphocytes are emerging as important elements in the events leading to joint destruction in rheumatoid arthritis (RA). However, B lymphocytes have not been studied in rheumatoid arthritis (RA)-associated lung disease. We performed a morphologic and quantitative analysis of B lymphocytes and plasma cells in RA-associated interstitial pneumonia (IP) in comparison with idiopathic IP and normal lungs. METHODS: Open-lung biopsy specimens from patients with RA-associated IP (n = 18), patients with idiopathic IP (n = 21), and control subjects (n = 11) were stained with antibodies to CD20 and CD138. Morphologic patterns of stained specimens were characterized and staining was quantified using computer-assisted image analysis. RESULTS: In RA-associated IP, marked follicular B cell hyperplasia was detected, which was limited almost entirely to peribronchiolar lymphoid aggregates. Plasma cells were also present in large numbers, but showed a more diffuse tissue infiltration. Quantification of B cells demonstrated higher cellularity in RA-associated IP (median 2.0%, interquartile range [IQR] 1.0-5.7) as compared with idiopathic IP (0.9%, IQR 0.5-2.1). Control specimens showed a significantly smaller number of B cells compared with both diseases (0.4%, IQR 0.1-1.3). In RA patients who were smokers and in those who were male, the proportion of CD20+ tissue areas further increased to 4.3% (IQR 1.0-5.8) and 3.9% (IQR 0.7-6.9), respectively. CONCLUSION: We demonstrated a significant follicular B cell hyperplasia in RA-associated IP. The differences between RA-associated IP and idiopathic IP imply a differential emphasis of B cell-mediated mechanisms in the 2 diseases despite radiologic and histologic similarities and provide a rationale for studying functional aspects of B cell involvement in the pathogenesis of RA-associated IP.