Showing papers in "Arthritis Care and Research in 2018"

2015 American College of Rheumatology Workforce Study: Supply and Demand Projections of Adult Rheumatology Workforce, 2015-2030.

Abstract: Objective To describe the character and composition of the 2015 US adult rheumatology workforce, evaluate workforce trends, and project supply and demand for clinical rheumatology care for 2015-2030. Methods The 2015 Workforce Study of Rheumatology Specialists in the US used primary and secondary data sources to estimate the baseline adult rheumatology workforce and determine demographic and geographic factors relevant to workforce modeling. Supply and demand was projected through 2030, utilizing data-driven estimations regarding the proportion and clinical full-time equivalent (FTE) of academic versus nonacademic practitioners. Results The 2015 adult workforce (physicians, nurse practitioners, and physician assistants) was estimated to be 6,013 providers (5,415 clinical FTE). At baseline, the estimated demand exceeded the supply of clinical FTE by 700 (12.9%). By 2030, the supply of rheumatology clinical providers is projected to fall to 4,882 providers, or 4,051 clinical FTE (a 25.2% decrease in supply from 2015 baseline levels). Demand in 2030 is projected to exceed supply by 4,133 clinical FTE (102%). Conclusion The adult rheumatology workforce projections reflect a major demographic and geographic shift that will significantly impact the supply of the future workforce by 2030. These shifts include baby-boomer retirements, a millennial predominance, and an increase of female and part-time providers, in parallel with an increased demand for adult rheumatology care due to the growing and aging US population. Regional and innovative strategies will be necessary to manage access to care and reduce barriers to care for rheumatology patients.

Medical expenditures and earnings losses among US adults with arthritis in 2013

Abstract: Objective We estimated the economic impact of arthritis using 2013 US Medical Expenditure Panel Survey (MEPS) data. Methods We calculated arthritis-attributable and all-cause medical expenditures for adults age ≥ 18 years and arthritis-attributable earnings losses among those 18-64 years who had ever worked. We calculated arthritis-attributable costs using multi-stage regression-based methods, and conducted sensitivity analyses to estimate costs for two other arthritis definitions in MEPS. Results In 2013, estimated total national arthritis-attributable medical expenditures were $139.8 billion (range= $135.9 - $157.5). Across expenditure categories, ambulatory care expenditures accounted for nearly half of arthritis-attributable expenditures. All-cause expenditures among adults with arthritis represented 51% of the $1.2 trillion national medical expenditures among all US adults in MEPS. Estimated total national arthritis-attributable earning losses were $163.7 billion (range= $163.7 - $170.0). The percentage with arthritis who worked in the past year was 7.2 percentage points lower than those without arthritis (76.8%; 95% CI= 75.0-78.6 and 84.0%; 95% CI= 82.5-85.5, respectively; adjusted for socio-demographics and chronic conditions). Total arthritis-attributable medical expenditures and earnings losses were $303.5 billion (range=$303.5 - $326.9). Conclusion Total national arthritis-attributable medical care expenditures and earnings losses among adults with arthritis were $303.5 billion in 2013. High arthritis-attributable medical expenditures might be reduced by greater efforts to reduce pain and improve function. The high earnings losses were largely attributable to the substantially lower prevalence of working among those with arthritis compared with those without, signaling the need for interventions that keep people with arthritis in the work force. This article is protected by copyright. All rights reserved.

Performance of Antinuclear Antibodies for Classifying Systemic Lupus Erythematosus: A Systematic Literature Review and Meta-Regression of Diagnostic Data

Abstract: Objective: To review the published literature on the performance of indirect immunofluorescence (IIF)-HEp-2 ANA testing for classification of SLE. Methods: A systematic literature search was conducted in the MEDLINE, EMBASE and COCHRANE databases for articles published between January 1990 and October 2015. The research question was structured according to PICO (Population, Intervention, Comparator, Outcome) format rules, and PRISMA recommendations were followed where appropriate. Meta-regression analysis for diagnostic tests was performed, using the ANA titer as independent variable while sensitivity and specificity were dependent variables. Results: Of 4,483 publications screened, 62 matched the eligibility criteria, and another two articles were identified through reference analysis. The included studies comprised 13,080 SLE patients in total, of whom 12,542 (95.9%) were reported to be IIF-ANA positive at various titers. For ANA at titers of 1:40, 1:80, 1:160, and 1:320, meta-regression gave sensitivity values of 98.4% (95% confidence interval [CI] 97.6-99.0%), 97.8% (CI 96.8-98.5%), 95.8% (CI 94.1-97.1%) and 86.0% (CI 77.0-91.9%), respectively. The corresponding specificities were 66.9% (CI 57.8-74.9%), 74.7% (CI 66.7-81.3%), 86.2% (CI 80.4-90.5%) and 96.6% (CI 93.9-98.1%), respectively. Conclusion: The results of this systematic literature review and meta-regression confirm that IIF-ANA have high sensitivity for SLE. ANA at a titer of 1:80 have sufficiently high sensitivity to be considered as an entry criterion for SLE classification criteria, i.e. formally test other classification criteria for SLE only if ANA of at least 1:80 have been found. This article is protected by copyright. All rights reserved.

Consensus Treatment Plans for Chronic Nonbacterial Osteomyelitis Refractory to Nonsteroidal Antiinflammatory Drugs and/or With Active Spinal Lesions.

Abstract: Objective To develop standardized treatment regimens for chronic nonbacterial osteomyelitis (CNO), also known as chronic recurrent multifocal osteomyelitis (CRMO) to enable comparative effectiveness treatment studies. Methods Virtual and face-to-face discussions and meetings were held within the CNO subgroup of the Childhood Arthritis and Rheumatology Research Alliance (CARRA). A literature search was conducted, and CARRA membership was surveyed to evaluate available treatment data and identify current treatment practices. Nominal group technique was used to achieve consensus on treatment plans for CNO refractory to non-steroidal anti-inflammatory drug (NSAID) monotherapy and/or with active spinal lesions. Results Three consensus treatment plans (CTPs) were developed for the first 12 months of therapy for CNO patients refractory to NSAID monotherapy and/or with active spinal lesions. The three CTPs are: (1) methotrexate or sulfasalazine, (2) tumor necrosis factor (TNF)-alpha inhibitors with optional use of methotrexate, and (3) bisphosphonates. Short courses of glucocorticoids and continuation of NSAIDs are permitted for all regimens. Consensus was achieved on these CTPs among CARRA members. Consensus was also reached on subject eligibility criteria, initial evaluations that should be conducted prior to the initiation of CTPs, and data items to collect to assess treatment response. Conclusion Three consensus treatment plans were developed for pediatric patients with CNO refractory to NSAIDs and/or with active spinal lesions. Use of these CTPs will provide additional information on efficacy and will generate meaningful data for comparative effectiveness research in CNO. This article is protected by copyright. All rights reserved.

Tele-Health Followup Strategy for Tight Control of Disease Activity in Rheumatoid Arthritis: Results of a Randomized Controlled Trial

Abstract: Objective To test the effect of patient-reported outcome (PRO)–based tele-health followup for tight control of disease activity in patients with rheumatoid arthritis (RA), and the differences between tele-health followup performed by rheumatologists or rheumatology nurses Methods A total of 294 patients were randomized (1:1:1) to either PRO-based tele-health followup carried out by a nurse (PRO-TN) or a rheumatologist (PRO-TR), or conventional outpatient followup by physicians The primary outcome was a change in the Disease Activity Score in 28 joints (DAS28) after week 52 Secondary outcomes were physical function, quality of life, and self-efficacy The noninferiority margin was a DAS28 score change of 06 Mean differences were estimated following per protocol, intent-to-treat (ITT), and multivariate imputation analysis Results Overall, patients had low disease activity at baseline and end followup Demographics and baseline characteristics were similar between groups Noninferiority was established for the DAS28 In the ITT analysis, mean differences in the DAS28 score between PRO-TR versus control were −010 (90% confidence interval [90% CI] −030, 013) and −019 (90% CI −041, 002) between PRO-TN versus control When including 1 yearly visit to the outpatient clinic, patients in PRO-TN had mean ± SD 172 ± 103 visits/year, PRO-TR had 175 ± 103 visits/year, and controls had 415 ± 10 visits/year This included extra visits due to inflammatory flare Conclusion Among RA patients with low disease activity or remission, a PRO-based tele-health followup for tight control of disease activity in RA can achieve similar disease control as conventional outpatient followup The degree of disease control did not differ between patients seen by rheumatologists or rheumatology nurses

An International Multispecialty Validation Study of the IgG4-Related Disease Responder Index.

Abstract: OBJECTIVE IgG4-related disease (IgG4-RD) can cause fibroinflammatory lesions in nearly any organ, leading to organ dysfunction and failure. The IgG4-RD Responder Index (RI) was developed to help investigators assess the efficacy of treatment in a structured manner. The aim of this study was to validate the RI in a multinational investigation. METHODS The RI guides investigators through assessments of disease activity and damage in 25 domains, incorporating higher weights for disease manifestations that require urgent treatment or that worsen despite treatment. After a training exercise, investigators reviewed 12 written IgG4-RD vignettes based on real patients. Investigators calculated both an RI score as well as a physician's global assessment (PhGA) score for each vignette. In a longitudinal assessment, 3 investigators used the RI in 15 patients with newly active disease who were followed up over serial visits after treatment. We assessed interrater and intrarater reliability, precision, validity, and responsiveness. RESULTS The 26 physician investigators included representatives from 6 specialties and 9 countries. The interrater and intrarater reliability of the RI was strong (0.89 and 0.69, respectively). Correlations (construct validity) between the RI and PhGA were high (Spearman's r = 0.9, P < 0.0001). The RI was sensitive to change (discriminant validity). Following treatment, there was significant improvement in the RI score (mean change 10.5 [95% confidence interval (95% CI) 5.4-12], P < 0.001), which correlated with the change in the PhGA. Urgent disease and damage were captured effectively. DISCUSSION In this international, multispecialty study, we observed that the RI is a valid and reliable disease activity assessment tool that can be used to measure response to therapy.

Developing and Refining New Candidate Criteria for Systemic Lupus Erythematosus Classification: An International Collaboration.

Abstract: Objectives. We aimed to define candidate criteria within multi-phase development of SLE classification criteria, jointly supported by EULAR and ACR. Prior steps included item generation and reduction by Delphi exercise, further narrowed to 21 items in a Nominal Group Technique exercise. Our objectives were to apply an evidence-based approach to the 21 candidate criteria, and to develop hierarchical organization of criteria within domains. Methods. A literature review identified the sensitivity and specificity of the 21 candidate criteria. Data on the performance of ANA as an entry criteria and operating characteristics of the candidate criteria in early SLE patients were evaluated. Candidate criteria were hierarchically organized into clinical and immunologic domains, and definitions were refined in an iterative process. Results. Based on the data, consensus was reached to use a positive ANA of ≥1:80 titer (HEp2 cells immunofluorescence) as an entry criterion and to have seven clinical and three immunologic domains, with hierarchical organization of criteria within domains. Definitions of the candidate criteria were specified. Conclusion. Using a data-driven process, consensus was reached on new, refined criteria definitions and organization based on operating characteristics. This work will be followed by a multicriteria decision analysis exercise to weight criteria and to identify a threshold score for classification on a continuous probability scale. This article is protected by copyright. All rights reserved.

Effect of Biologic Therapy on Clinical and Laboratory Features of Macrophage Activation Syndrome Associated With Systemic Juvenile Idiopathic Arthritis

Abstract: Objective: To assess performance of the 2016 macrophage activation syndrome (MAS) classification criteria for patients with systemic juvenile idiopathic arthritis (systemic JIA) who develop MAS while treated with biologic medications. Methods: A systematic literature review was performed to identify patients with MAS while treated with IL-1 and IL-6 blocking agents. Clinical and laboratory information was compared to a large previously compiled historical cohort. Results: Eighteen publications were identified, and after removing duplicates 35 patients treated with canakinumab and 49 patients with tocilizumab were available for analysis; 5 anakinra-treated patients were excluded due to limited numbers. MAS classification criteria were less likely to classify tocilizumab treated patients as having MAS compared to the historical cohort or canakinumab treated patients (56.7% vs. 78.5% and 84%, p<0.01). Patients who developed MAS while treated with canakinumab trended towards lower ferritin at MAS onset than the historical cohort (4,050 vs. 5,353 ng/ml, p=0.18) but had no differences in other cardinal clinical or laboratory features. In comparison, patients who developed MAS while treated with tocilizumab were less likely febrile, and had notably lower ferritin (1,152 vs. 5,353 ng/ml, p<0.001). Other features of MAS were more pronounced in patients treated with tocilizumab, including lower platelet counts, lower fibrinogen and higher aspartate aminotransferase levels. Mortality rates for patients with MAS treated with tocilizumab or canakinumab were not significantly different from the historical cohort. Conclusions: These findings show substantial alterations in MAS features that may limit utility of defined criteria for diagnosis of systemic JIA patients treated with biologics. This article is protected by copyright. All rights reserved.

Cognitive Impairment in Rheumatoid Arthritis: A Systematic Review

Abstract: Objectives: Rheumatoid Arthritis (RA) is not commonly associated with central nervous system and brain changes. However a number of studies have reported high rates of cognitive impairment (CI) in adults with RA. The objective of this systematic review was to identify and explore the rates and types of CI in RA. Methods: Multiple databases were searched including a time frame between 1994 to 2016 to identify studies that have included: (i) adults with RA; (ii) standardized neuropsychological tests; and (iii) sufficient information to ascertain the relationship between CI and demographic, clinical and psychology factors. Of 1,980 titles, 75 were retained at abstract level, 36 at full-text level and 15 studies in the final review. These were evaluated using a modified Newcastle-Ottawa Evaluation Scale and the findings were synthesized using a narrative approach. Results: Ten out of 15 studies compared RA to other clinical and/or control groups. Based on summed effect size analyses, individuals with RA significantly under-performed on cognitive function tests compared to the control groups; particularly on verbal function, memory, and attention. Less clear differences were found between RA and other clinical groups. Some demographic (age, education), clinical (disease activity) and psychological (depression) factors were associated with CI but inconsistently so across studies. A number of limitations were identified: small and predominantly female samples, limited cognitive domain inclusion, lack of study details, and management of confounding variables. Conclusions: There is evidence of CI in adults with RA. Further studies are required to confirm prevalence rates and examine potential mechanisms.

Increased Burden of Psychiatric Disorders in Rheumatoid Arthritis.

Abstract: Objective We estimated the incidence and prevalence of depression, anxiety disorder, bipolar disorder, and schizophrenia in a population-based cohort with rheumatoid arthritis (RA) as compared to an age-, sex-, and geographically matched cohort without RA. Methods Using population-based administrative health data from Manitoba, Canada, we identified persons with incident RA between 1989 and 2012, and a cohort from the general population matched 5:1 on year of birth, sex, and region of residence. We applied validated algorithms for depression, anxiety disorder, bipolar disorder, and schizophrenia to determine the annual incidence of these conditions after the diagnosis of RA, and their lifetime and annual period prevalence. We compared findings between cohorts using negative binomial regression models. Results We identified 10,206 incident cases of RA and 50,960 matched individuals. After adjustment for age, sex, socioeconomic status, region of residence, number of physician visits, and year, the incidence of depression was higher in the RA cohort over the study period (incidence rate ratio [IRR] 1.46 [95% confidence interval (95% CI) 1.35-1.58]), as was the incidence of anxiety disorder (IRR 1.24 [95% CI 1.15-1.34]) and bipolar disorder (IRR 1.21 [95% CI 1.00-1.47]). The incidence of schizophrenia did not differ between groups (IRR 0.96 [95% CI 0.61-1.50]). Incidence rates of psychiatric disorders declined minimally over time. The lifetime and annual period prevalence of depression and anxiety disorder were also higher in the RA than in the matched cohort over the study period. Conclusion The incidence and prevalence of depression, anxiety disorder, and bipolar disorder are elevated in the RA population as compared to a matched population.

Intentional Weight Loss in Overweight and Obese Patients With Knee Osteoarthritis: Is More Better?

Abstract: OBJECTIVE To determine the dose response effect of weight loss on clinical and mechanistic outcomes in overweight and obese adults with knee osteoarthritis (OA). METHODS This is a secondary analysis of the diet-induced weight loss only (D) and diet-induced weight loss plus exercise (D + E) groups in the Intensive Diet and Exercise for Arthritis randomized controlled clinical trial. The 240 participants were overweight and obese older community-dwelling adults with pain and radiographic knee OA. Participants were assigned to 1 of 4 groups according to weight loss achieved over an 18-month period: 20% (≥20% group). RESULTS There were significant dose responses to weight loss for pain (P = 0.01), function (P = 0.0006), 6-minute walk distance (P < 0.0001), physical (P = 0.0004) and mental (P = 0.03) health-related quality of life (HRQoL), knee joint compressive force (P < 0.0001), and interleukin-6 (P = 0.002). Greater weight loss resulted in superior clinical and mechanstic outcomes, with the highest weight loss group (≥20% group) distinguishing itself on all measures compared with the <5% and ≥5% groups; the ≥20% group had 25% less pain and better function compared with the ≥10% group and significantly (P = 0.006) better physical HRQoL. CONCLUSION Long-term weight loss of 10-19.9% of baseline body weight has substantial clinical and mechanistic benefits compared with less weight loss. The value of an additional 10% weight loss includes significantly improved physical HRQoL and a clinically important reduction of pain and improvement in function.

Suppressing Inflammation in Rheumatoid Arthritis: Does Patient Global Assessment Blur the Target? A Practice-Based Call for a Paradigm Change.

Abstract: Objectives: In current management paradigms of Rheumatoid Arthritis (RA), patient global assessment (PGA) is crucial to decide whether a patient has attained remission (target) or needs reinforced therapy. We investigated whether the clinical and psychological determinants of PGA are appropriate to support this important role. Methods: This was a cross-sectional, single centre study including consecutive ambulatory RA patients. Data collection comprised swollen (SJC28) and tender joint counts (TJC28), C-Reactive protein (CRP), PGA, pain, fatigue, function, anxiety, depression, happiness, personality traits, and comorbidities. Remission was categorised using ACR/EULAR Boolean-based criteria: remission, near-remission (only PGA>1) and non-remission. A binary definition without PGA (3v-Remission) was also studied. Univariable and multivariable analyses were used to identify explanatory variables of PGA in each remission state. Results: 309 patients were included (remission: 9.4%; near-remission: 37.2%; non-remission: 53.4%). Patients in near-remission were indistinguishable from remission regarding disease activity, but described a disease impact similar to those in non-remission. In multivariable analyses, PGA in near-remission was explained (R2adjusted=.50) by fatigue, pain, anxiety and function. Fatigue and pain had no relationship with disease activity measures. Conclusion: In RA, a consensually acceptable level of disease activity (SJC28, TJC28, and CRP≤1) does not equate to low disease impact: a large proportion of these patients are considered in non-remission solely due to PGA. PGA mainly reflects fatigue, pain, function, and psychological domains, which are inadequate to define the target for immunosuppressive therapy. This suggests that clinical practice should be guided by two separate remission targets: inflammation (3v-Remission) and disease impact. This article is protected by copyright. All rights reserved.

Physical Activity to Reduce Fatigue in Rheumatoid Arthritis: A Randomized Controlled Trial.

Abstract: Objective Effective treatments for rheumatoid arthritis (RA) fatigue are limited. We tested the effect of a pedometer-based intervention on increasing physical activity and decreasing fatigue among individuals with RA. Methods Participants completed baseline questionnaires; had 1 week of activity monitoring; were randomized to control (education [EDUC]), pedometer and step-monitoring diary (PED), or pedometer and diary plus step targets (PED+) groups, and were followed for 21 weeks. At week 10, questionnaires were administered by phone to all participants. During the final week, all participants again had 1 week of activity monitoring. Primary outcomes were changes in average weekly steps and fatigue (Patient-Reported Outcomes Measurement Information System 7-item questionnaire) from baseline to week 21. Secondary outcomes were self-reported disease activity, physical function, pain interference, and depressive symptoms. Changes in steps were tested using a linear mixed model. Changes in fatigue were tested with repeated-measures models, including baseline, week-10, and week-21 scores. Results A total of 96 individuals participated. Eight did not complete the 21-week assessments. Both intervention groups significantly increased steps (+1,441 [P = 0.004] for PED and +1,656 [P = 0.001] for PED+), and the EDUC group decreased steps (-747 [P = 0.14]) (group-by-time interaction P = 0.0025). Between-group changes in fatigue were not significantly different (interaction P = 0.21). Mean changes in fatigue scores from baseline to week 21 were -1.6 (with-group P = 0.26), -3.2 (P = 0.02), and -4.8 (P = 0.0002) for EDUC, PED, and PED+ groups, respectively. Function and self-reported disease activity also improved in the PED and PED+ groups. Conclusion Provision of pedometers, with and without providing step targets, was successful in increasing activity levels and decreasing fatigue in this sample of individuals with RA.

Internet Cognitive-Behavioral Therapy for Depression in Older Adults With Knee Osteoarthritis: A Randomized Controlled Trial.

Abstract: Objective To determine the efficacy of an internet-based cognitive–behavioral therapy (iCBT) program for depression in older adults with osteoarthritis (OA) of the knee and comorbid major depressive disorder (MDD). Methods We conducted a randomized controlled trial in 69 adults (ages ≥50 years) meeting criteria for MDD and OA of the knee with 1-week postintervention (week 11) and 3-month followup (week 24) end points. Patients were allocated to either a 10-week iCBT program for depression added to treatment as usual (TAU) or to a TAU control group. Primary outcomes were depression symptoms (9-Item Patient Health Questionnaire [PHQ-9]) and psychological distress (Kessler-10 [K-10]). Secondary outcomes included arthritis self-efficacy (Arthritis Self-Efficacy Scale [ASES]), OA pain, stiffness, physical function (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]), and physical and mental health (Short Form 12-Item health survey physical component and mental component summaries). Depression status was assessed by blinded diagnostic interview (the Mini-International Neuropsychiatric Interview) at intake and followup. Results Intent-to-treat analyses indicated between-group superiority of iCBT over TAU on the primary outcomes (PHQ-9: Hedges g = 1.01, 95% confidence interval [95% CI] 0.47, 1.54; K-10: Hedges g = 0.75, 95% CI 0.23, 1.28), at postintervention and 3-month followup (PHQ-9: Hedges g = 0.90, 95% CI 0.36, 1.44; K-10: Hedges g = 0.94, 95% CI 0.41, 1.48), and on secondary OA-specific measures (ASES: Hedges g = −0.81, 95% CI −0.29, −1.33; WOMAC: Hedges g = 0.56–0.65, 95% CI 0.04, 1.18) at the 3-month followup. The majority of iCBT participants (84%) no longer met diagnostic criteria at 3-month followup. Conclusion Results support the efficacy of an iCBT program (requiring no face-to-face contact) for depression in individuals with comorbid depression and OA of the knee. Importantly, the benefits of the program extended beyond reduced depressive symptoms and distress to include increased self-efficacy and improved pain, stiffness, and physical function at followup.

Changes in Physical Activity After Total Hip or Knee Arthroplasty: A Systematic Review and Meta-Analysis of Six- and Twelve-Month Outcomes

Abstract: Objective Little is known about the extent to which physical activity (PA) changes following total knee or hip joint replacement relative to pain, physical function and quality of life. Our objective was to conduct a systematic review and meta-analysis on changes in PA relative to pain, quality of life and physical function after total knee or hip joint replacement. Methods We searched PubMed (Medline), Embase and Cinahl, for peer-reviewed, English-language cohort studies measuring PA with an accelerometer from pre-surgery to post-surgery. Random-effects models were used to produce standardized mean differences (SMDs) for PA, quality of life, pain, and physical function outcomes. Heterogeneity was measured with I2. Results Seven studies (336 participants) met eligibility criteria. No significant increase in PA was found at 6-months (SMD 0.14; 95% CI -0.05 to 0.34; I2=0%) and a small-moderate significant effect was found for increasing PA at 12-months (SMD 0.43; 95% CI 0.22 to 0.64; I2=0%). Large improvements at 6-months in physical function (SMD 0.97; 95% CI 0.12 to 1.82; I2=92.3%), pain (SMD -1.47; 95% CI -2.28 to -0.65; I2=91.6%), and quality of life (SMD 1.02; 95% CI 0.30 to 1.74; I2=83.2%) were found. Conclusions Physical activity did not change at 6-months and a small-moderate improvement was found at 12-months post-surgery, despite large improvements in quality of life, pain, and physical function. Reasons for the lack of increased PA are unknown but may be behavioral in nature as sedentary lifestyle is difficult to change. Changing sedentary behavior should be a future focus among this subgroup. This article is protected by copyright. All rights reserved.

Examination of Hydroxychloroquine Use and Hemolytic Anemia in G6PDH-Deficient Patients.

Abstract: Objective: Some sources urge caution when prescribing hydroxychloroquine (HCQ) to patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, presumably due to a risk of hemolytic anemia. There is limited published data, however, to support this risk. Additionally, not all patients with G6PD deficiency are at similar risk for hemolysis, and people with the African variant are at particularly low risk. Through a retrospective chart review, we aimed to quantify the frequency of G6PD deficient patients with hemolysis attributed to HCQ. Methods: We identified Duke Rheumatology patients with HCQ usage and a measured G6PD level. A retrospective chart review was performed, recording demographics, G6PD levels, episodes of anemia, laboratory values consistent with hemolysis, and HCQ use. Results: Of the 275 patients reviewed, 84% were female, 46% African American and 48% Caucasian. The leading diagnoses were lupus (32%), rheumatoid arthritis (29%), and inflammatory arthritis (14%). Only 4% of patients were G6PD deficient, all African American. Two G6PD-deficient patients had hemolysis during severe lupus flares that occurred while not taking HCQ. There were no reported episodes of hemolysis in over 700 months of HCQ exposure among the 11 G6PD-deficient patients. Conclusion: This is the largest study to date evaluating G6PD deficiency with concurrent use of HCQ. Among 11 patients with G6PD deficiency, 2 had episodes of hemolysis, but neither occurred during HCQ therapy. These data do not support routine G6PD level measurement or withholding HCQ therapy among African American patients with G6PD deficiency. This article is protected by copyright. All rights reserved.

Impact of Osteoarthritis on Difficulty Walking: A Population-Based Study

Abstract: Objective: To assess the relationship of hip and knee osteoarthritis (OA) to walking difficulty Methods: A population cohort aged ≥55 years recruited from 1996-98 (n=28,451) completed a standardized questionnaire assessing demographics, health conditions, joint complaints and functional limitations, including difficulty walking in the past 3 months Survey data were linked to health administrative databases; self-report and administrative data were used to identify health conditions Hip/knee OA was defined as self-reported swelling, pain, or stiffness in a hip or knee lasting ≥6 weeks in the past 3 months without an inflammatory arthritis diagnosis Using multivariable logistic regression, we examined the determinants of walking difficulty and constructed a clinical nomogram Results: 18,490 cohort participants were eligible (mean age 68 years, 60% female) 25% reported difficulty walking Difficulty walking was significantly and independently associated with older age, female sex, body mass index, and several health conditions; of the conditions examined, the likelihood of walking difficulty was greatest with hip and knee OA and increased with number of hips/knees joints affected The predicted probability of difficulty walking for a 60-year-old middle-income, normal-weight woman was 5-10% with no health conditions, 10-20% with diabetes and CV disease, 40% with OA in two hips/knees, 60-70% with diabetes, CV disease and OA in two hips/knees, and 80% with diabetes, CV disease and OA in all hips/knees Conclusion: In a population cohort, symptomatic hip/knee OA was the strongest contributor to walking difficulty Given the importance of walking to engagement in physical activity for chronic disease management, greater attention to OA is warranted This article is protected by copyright All rights reserved

Association Between Pain Sensitization and Disease Activity in Patients With Rheumatoid Arthritis: A Cross-Sectional Study

Abstract: Objective. Pain sensitization may contribute to pain severity in rheumatoid arthritis (RA), impacting assessment of disease activity. We examined whether pain processing mechanisms were associated with disease activity among RA patients with active disease. Methods. This study includes 139 subjects enrolled in the Central Pain in Rheumatoid Arthritis cohort. Subjects underwent quantitative sensory testing (QST), including assessment of pressure pain thresholds (PPTs) at multiple sites, conditioned pain modulation, and temporal summation. RA disease activity was assessed using the Clinical Disease Activity Index (CDAI) and its components. We examined cross-sectional associations between QST measures and disease activity using linear regression. Results. Low PPTs (high pain sensitization) at all sites were associated with high CDAI scores (P ≤ 0.03) and tender joint counts (P ≤ 0.002). Associations between PPTs and patient global assessments were also seen at most sites. High temporal summation at the forearm (also reflecting high pain sensitization) was significantly associated with high CDAI scores (P = 0.02), patient global assessment (P = 0.0006), evaluator global assessment (P = 0.01) and tender joint counts (P = 0.02). Conversely, conditioned pain modulation (a measure of descending inhibitory pain pathways) was only associated with tender joint count (P = 0.03). Conclusion. High pain sensitization is associated with elevations in disease activity measures. Longitudinal studies are underway to elucidate the cause-effect relationships between pain sensitization and inflammatory disease activity in RA. This article is protected by copyright. All rights reserved.

Multinational Qualitative Research Study Exploring the Patient Experience of Raynaud's Phenomenon in Systemic Sclerosis

Abstract: Objective. Raynaud’s phenomenon (RP) is the most common manifestation of systemic sclerosis (SSc). RP is an episodic phenomenon, not easily assessed in the clinic, leading to reliance on self-report. A thorough understanding of the patient experience of SSc-RP is essential to ensuring that patient-reported outcome (PRO) instruments capture domains important to the target patient population. We report the findings of an international qualitative research study investigating the patient experience of SSc-RP. Methods. Focus groups of SSc patients were conducted across 3 scleroderma centers in the US and UK, using a topic guide and a priori purposive sampling framework devised by qualitative researchers, SSc patients, and SSc experts. Focus groups were audio recorded, transcribed, anonymized, and analyzed using inductive thematic analysis. Focus groups were conducted until thematic saturation was achieved. Results. Forty SSc patients participated in 6 focus groups conducted in Bath (UK), New Orleans (Louisiana), and Pittsburgh (Pennsylvania). Seven major themes were identified that encapsulate the patient experience of SSc-RP: physical symptoms, emotional impact, triggers and exacerbating factors, constant vigilance and self-management, impact on daily life, uncertainty, and adaptation. The interrelationship of the 7 constituent themes can be arranged within a conceptual map of SSc-RP. Conclusion. We have explored the patient experience of SSc-RP in a diverse and representative SSc cohort and identified a complex interplay of experiences that result in significant impact. Work to develop a novel PRO instrument for assessing the severity and impact of SSc-RP, comprising domains/items grounded in the patient experiences of SSc-RP identified in this study, is underway

Restrictive Use of Oral Glucocorticoids in Systemic Lupus Erythematosus and Prevention of Damage Without Worsening Long-Term Disease Control: An Observational Study.

Abstract: Objective: To analyse the influence of two different treatment strategies on general and specific damage accrual in patients with SLE. Methods: Two cohorts were identified according to the responsible physicians: 1.-patients treated at the Autoimmune Diseases Unit (ADU); 2.-patients treated by other members of the Internal Medicine Department (IM). Members of the ADU worked with a protocol including the universal prescription of hydroxychloroquine (HCQ), the use of maximum oral prednisone doses ≤30mg/day and maintenance therapy with ≤5mg/day, by using methyl-prednisolone pulses and/or early immunosuppressants (IS). We analysed the influence of these two treatment strategies on damage accrual, both general and domain specific, attributed to glucocorticoids (GCs), cardiovascular disease (CV), SLE and unclassified, since the diagnosis of disease in patients with a follow-up ≥5 years. Results: 74 patients were included in group ADU and 213 in group IM. They were comparable for most demographic and lupus-related variables. ADU patients received prednisone later and at lower doses, more methyl-prednisolone pulses, earlier IS and more HCQ (p<0.05 for all comparisons). The SLEDAI decreased similarly in both cohorts (p=0.4). Patients in group ADU were less likely to accrue any damage (p=0.007). They accrued less GCs-related (adjusted HR 0.23, 95%CI 0.07-0.80), CV (adjusted HR 0.28, 95%CI 0.08-0.95) and unclassified damage (adjusted HR 0.58, 95%CI 0.3-1.1). Both groups accrued similar SLE-related damage (adjusted HR 0.84, 95%IC 0.40-1.75). Conclusion: The use of reduced oral prednisone doses, which was possible by combining different therapies, reduced GCs-related damage and improved cardiovascular prognosis without increasing damage caused by SLE. This article is protected by copyright. All rights reserved.

Physical Functioning, Pain, and Health-Related Quality of Life in Adults With Juvenile Idiopathic Arthritis: A Longitudinal 30-Year Followup Study.

Abstract: Objectives: To describe physical functioning, pain, and health-related quality of life (HRQOL) in adults with Juvenile idiopathic arthritis (JIA), investigate changes over time, and identify predictors of poorer HRQOL after 30 years of disease duration. Methods: Patients (N=176) clinically examined after 15 years were reassessed with the Health Assessment Questionnaire Disability Index (HAQ-DI), Visual Analogue Scale Pain (VAS pain) and Medical Outcome Study 36-item Short Form (SF-36) after 23 and 30 years. Patients with signs of active disease after a minimum of 15 years were clinically examined again at 30 years. Patients were compared to matched controls. Results: At 30-year follow-up, 82 patients (47%) had HAQ-DI score >0 and median VAS pain score in patients was 0.6 (range 0-10). Patients had lower physical component summary scores (PCS) compared with controls (p<0.001), and this was evident for patients both with and without clinical remission (p≤0.01). No group differences were found in mental component summary scores. Patients also scored worse than controls on all SF-36 subscales (p≤0.01) except mental health. PCS scores worsened significantly between the 15 and 30-year follow-ups (p=0.001). Worse HAQ-DI, VAS pain, and patient's global assessment of wellbeing scores, and receiving disability/social living allowance at 30 years were correlates of lower PCS. Worse HAQ-DI, patient's global assessment of wellbeing, and VAS fatigue at 15-year follow-up predicted lower PCS at 30-year follow-up. Conclusion: JIA had a detrimental effect on physical HRQOL as measured by PCS. The strongest correlates were physical disabilities, pain, fatigue, wellbeing and receiving disability/social living allowance. This article is protected by copyright. All rights reserved.

Disclosure of Personalized Rheumatoid Arthritis Risk Using Genetics, Biomarkers, and Lifestyle Factors to Motivate Health Behavior Improvements: A Randomized Controlled Trial.

Abstract: Objective To determine the effect of disclosure of rheumatoid arthritis (RA) risk personalized with genetics, biomarkers, and lifestyle factors on health behavior intentions. Methods We performed a randomized controlled trial among first-degree relatives without RA. Subjects assigned to the Personalized Risk Estimator for RA (PRE-RA) group received the web-based PRE-RA tool for RA risk factor education and disclosure of personalized RA risk estimates including genotype/autoantibody results and behaviors (n=158). Subjects assigned to the comparison arm received standard RA education (n=80). The primary outcome was readiness for change based on the transtheoretical model, using validated contemplation ladder scales. Increased motivation to improve RA risk-related behaviors (smoking, diet, exercise, or dental hygiene) was defined as an increase in any ladder score compared to baseline assessed immediately, 6 weeks, and 6 months post-intervention. Subjects reported behavior change at each visit. We performed intention-to-treat analyses using generalized estimating equations for the binary outcome. Results Subjects randomized to PRE-RA were more likely to increase ladder scores over post-intervention assessments (RR 1.23, 95%CI 1.01-1.51) than those randomized to non-personalized education. At 6 months, 63.9% of PRE-RA subjects and 50.0% of comparison subjects increased motivation to improve behaviors (age-adjusted difference 15.8%, 95%CI 2.8-28.8%). Compared to non-personalized education, more PRE-RA subjects increased fish intake (45.0% vs. 22.1%; p=0.005), brushed more frequently (40.7% vs. 22.9%; p=0.01), flossed more frequently (55.7% vs. 34.8%; p=0.004), and quit smoking (62.5% vs. 0.0% among 11 smokers; p=0.18). Conclusion Disclosure of RA risk personalized with genotype/biomarker results and behaviors increased motivation to improve RA risk-related behaviors. Personalized medicine approaches may motivate health behavior improvements for those at risk for RA and provide rationale for larger studies evaluating effects of behavior changes on clinical outcomes such as RA-related autoantibody production or RA development. This article is protected by copyright. All rights reserved.

Characterization of Patients With Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis in the US-Based Corrona Registry.

Abstract: Objective To describe the characteristics of patients with ankylosing spondylitis (AS) and patients with nonradiographic axial spondyloarthritis (SpA) in the US. Methods Demographics, clinical characteristics, patient-reported outcomes, and treatment characteristics of patients with AS and those with nonradiographic axial SpA were assessed at the time of enrollment in the Corrona Psoriatic Arthritis/Spondyloarthritis Registry. Patients with AS were defined as those who fulfilled the 1984 modified New York criteria for AS; patients with nonradiographic axial SpA were defined as all other patients with axial SpA who did not fulfill the radiology criterion. Results Of the 407 patients with a diagnosis of axial SpA who were included in this study, 310 had AS, and 97 had nonradiographic axial SpA. Although patients with nonradiographic axial SpA were younger and showed a trend toward a shorter symptom duration, the nonradiographic axial SpA and AS groups shared a similar disease burden, as reflected by comparisons of disease activity and function, quality of life, pain, fatigue, job absenteeism, and loss of work productivity (all P > 0.05). The proportions of patients with nonradiographic axial SpA and patients with AS who received prior biologic disease-modifying drugs (DMARDs) (74.2% and 64.8%, respectively) or were currently receiving biologic DMARDs (63.9% and 61.3%, respectively) were also similar (P > 0.05). Conclusion This was the first nationwide study to characterize patients with AS and nonradiographic axial SpA in the US. Consistent with studies published outside of the US, this study showed that patients with nonradiographic axial SpA and patients with AS shared a comparable degree of disease burden and had similar treatment patterns in clinical practice.

Projected Burden of Osteoarthritis and Rheumatoid Arthritis in Australia: A Population-Level Analysis

Abstract: Objective To forecast the prevalence and direct healthcare costs of osteoarthritis (OA) and rheumatoid arthritis (RA) in Australia to the year 2030. Methods An epidemiological model of the Australian population was developed. Data on the national prevalence of OA and RA were obtained from the Australian Bureau of Statistics (ABS) 2014-2015 National Health Survey. Future prevalence was estimated using ABS population projections for 2020, 2025 and 2030. Available government data on direct healthcare expenditure for OA and RA were modelled to forecast costs (in AUD) for the years 2020, 2025 and 2030, from the perspective of the Australian public healthcare system. Results The number of people with OA is expected to increase nationally from almost 2.2 million in 2015 to almost 3.1 million Australians in 2030. The number of people with RA is projected to increase from 422,309 in 2015 to 579,915 in 2030. Healthcare costs for OA were estimated to be over $2.1 billion in 2015; by the year 2030, these are forecast to exceed $2.9 billion ($970 for every person with the condition). Healthcare costs for RA were estimated to be over $550 million in 2015, including $273 million spent on biological disease-modifying anti-rheumatic drugs. Healthcare costs for RA are projected to rise to over $755 million by the year 2030. Conclusions OA and RA are costly conditions that will impose an increasing healthcare burden at the population level. These projections provide tangible data that can be utilised to map future health service provision to expected need. This article is protected by copyright. All rights reserved.

Medical Care Costs Associated with Rheumatoid Arthritis in the US: A Systematic Literature Review and Meta-analysis

Abstract: Objective Rheumatoid arthritis (RA) is a morbid, mortal, and costly condition without a cure. Treatments for RA have expanded over the last 2 decades, and direct medical costs may differ by types of treatments. There has not been a systematic literature review since the introduction of new RA treatments, including biologic disease-modifying antirheumatic drugs (bDMARDs). Methods We conducted a systematic literature review with meta-analysis of direct medical costs associated with RA patients cared for in the US since the marketing of the first bDMARD. Standard search strategies and sources were used, and data were extracted independently by 2 reviewers. The methods and quality of included studies were assessed. Total direct medical costs as well as RA-specific costs were calculated using random-effects meta-analysis. Subgroups of interest included Medicare patients and those using bDMARDs. Results We found 541 potentially relevant studies, and 12 articles met the selection criteria. The quality of studies varied: one-third were poor, one-third were fair, and one-third were good. Total direct medical costs were estimated at $12,509 (95% confidence interval [95% CI] 7,451-21,001) for all RA patients using any treatment regimen and $36,053 (95% CI 32,138-40,445) for bDMARD users. RA-specific costs were $3,723 (95% CI 2,408-5,762) for all RA patients using any treatment regimen and $20,262 (95% CI 17,480-23,487) for bDMARD users. Conclusion The total and disease-specific direct medical costs for patients with RA is substantial. Among bDMARD users, the cost of RA care is more than half of all direct medical costs.

Causes of death in rheumatoid arthritis: How do they compare to the general population?

Abstract: OBJECTIVE To compare mortality rates, underlying causes of death, excess mortality, and years of potential life lost (YPLL) among patients with rheumatoid arthritis (RA) relative to the general population. METHODS We studied an inception cohort of 87,114 Ontario-based RA patients and 348,456 age/sex/area-matched general population comparators from years 2000 to 2013. All-cause, cause-specific, and excess mortality rates, mortality rate ratios (MRRs), and the YPLL were estimated. RESULTS A total of 11,778 RA patients (14%) and 32,472 comparators (9%) died during 508,385 and 1,769,365 patient-years of follow-up, respectively, for corresponding mortality rates of 232 (95% confidence interval [95% CI] 228-236) and 184 (95% CI 182-186) per 10,000 patient-years. The leading causes of death in both groups were diseases of the circulatory system, cancer, and respiratory conditions. Increased mortality for all-cause and specific causes was observed in RA patients relative to the general population. MRRs were elevated for most causes of death. Age-specific mortality ratios illustrated a high excess mortality among RA patients <45 years of age for respiratory disease and circulatory disease. The YPLL for RA patients was 7,436 per 10,000 persons, compared with 4,083 YPLL among those without RA. CONCLUSION Among most causes of death, mortality rates were increased in RA patients relative to the general population. The potential life years lost (before the age of 75 years) among RA patients was roughly double that among those without RA, reflecting higher rate ratios for most causes of death and RA patients dying at earlier ages.

Efficacy of Mycophenolate Mofetil and Oral Cyclophosphamide on Skin Thickness: Post Hoc Analyses From Two Randomized Placebo-Controlled Trials.

Abstract: Objectives: To assess the efficacy of mycophenolate mofetil (MMF) and cyclophosphamide (CYC) on the modified Rodnan skin score (mRSS) in participants enrolled in the Scleroderma Lung Study (SLS)-I and II Methods: SLS-I participants received daily oral CYC or matching placebo for one year, whereas SLS-II participants received daily MMF for 2 years or daily oral CYC for 1 year followed by placebo for second year We assessed the impact of MMF and CYC on the mRSS in SLS-II over 24-month period We also compared the change in mRSS in patients with diffuse cutaneous systemic sclerosis (dcSSc) assigned to CYC and MMF in SLS-II and SLS-I vs placebo in SLS-I over a 24-month period using a linear mixed model Results: In SLS-II, the baseline (mean±SD) mRSS was 140±106 units for CYC and 153±104 units for MMF; 585% were classified as dcSSc CYC and MMF were associated with statistically significant improvements in mRSS from baseline over the period of 24 months in dcSSc (p< 005 at each time point) but there were no differences between the two groups In the dcSSc subgroup, the change in mRSS from baseline to all 6 month visits was similar in SLS-II groups— MMF, CYC, pooled cohort (MMF+ CYC) and SLS-I CYC groups and showed statistically significant improvements compared to SLS-I placebo at 12-, 18-, and 24-month period (p< 005) Conclusions: In SLS-II, MMF and CYC resulted in improvements in mRSS in dcSSc over 24 months In addition, MMF and CYC resulted in statistically significant improvements in mRSS in patients with dcSSc when compared with the SLS-I placebo group This article is protected by copyright All rights reserved

Efficacy of Hydroxychloroquine in Hand Osteoarthritis: A Randomized, Double‐Blind, Placebo‐Controlled Trial

Abstract: Objective To determine the symptom modifying effect of hydroxychloroquine (HCQ) in hand osteoarthritis (OA). Methods In this randomized, double blind, multicenter trial, patients with symptomatic hand OA received either HCQ 400 mg once a day or placebo during 24 weeks. The primary outcome was change of pain measured on a 100 mm VAS at 24 weeks. Secondary outcomes included decrease of pain at week 6 and 12 and change in AUSCAN and AIMS2-SF total scores. Results 196 patients were included (placebo n=98, HCQ n=98). Mean (SD) age was 58.0 (7.6) years; 86% were female. Baseline mean pain VAS (standard deviation) was 44.9 (22.9) mm in the placebo group and 43.2 (22.3) mm in the HCQ group. At 24 weeks, change in pain VAS was not significantly different between both groups (imputed mean VAS 42.7 in the HCQ group versus 45.3 in the placebo group after 24 weeks), as was the case in pain VAS at week 6 and 12. Changes in AUSCAN total score and AIMS2-SF total score in both groups were similar between the groups. 24 patients in the placebo group and 21 patients in the HCQ group reported ≥ 1 adverse events (AE). In the HCQ group, 3 patients reported a severe allergic reaction. Fifteen patients withdrew from the study (5 placebo, 10 HCQ group) due to adverse events. Conclusions Treatment with HCQ (24 weeks) is not effective in reducing the symptoms of hand OA compared to placebo. This article is protected by copyright. All rights reserved.

Cerebrovascular Events in Systemic Lupus Erythematosus: Results From an International Inception Cohort Study

Abstract: OBJECTIVE: To determine the frequency, associations and outcomes of cerebrovascular events (CerVEs) in a multi-ethnic/racial, prospective, SLE disease inception cohort. METHODS: Patients were assessed annually for 19 neuropsychiatric (NP) events including 5 types of CerVEs: (i) Stroke; (ii) Transient ischemia; (iii) Chronic multifocal ischemia; (iv) Subarachnoid/intracranial hemorrhage; (v) Sinus thrombosis. Global disease activity (SLEDAI-2K), SLICC/ACR damage index (SDI) and SF-36 scores were collected. Time to event, linear and logistic regressions and multi-state models were used as appropriate. RESULTS: Of 1,826 SLE patients, 88.8% were female, 48.8% Caucasian, mean±SD age 35.1±13.3 years, disease duration 5.6±4.2 months and follow-up 6.6±4.1 years. CerVEs were the fourth most frequent NP event: 82/1,826 (4.5%) patients had 109 events, 103/109 (94.5%) were attributed to SLE and 44/109 (40.4%) were identified at enrollment. The predominant events were stroke [60/109 (55.0%)] and transient ischemia [28/109 (25.7%)]. CerVEs were associated with other NP events attributed to SLE (HR (95% CI): (3.16; 1.73-5.75) (p<0.001), non-SLE NP (2.60; 1.49-4.51) (p<0.001), African ancestry at US SLICC sites (2.04; 1.01-4.13) (p=0.047) and organ damage (p=0.041). Lupus anticoagulant increased the risk of first stroke and sinus thrombosis [2.23 (1.11, 4.45) p=.024] and TIA [3.01 (1.15, 7.90) p=0.025]. Physician assessment indicated resolution or improvement in the majority but patients reported sustained reduction in SF-36 summary and subscale scores following CerVEs (P<0.0001). CONCLUSION: CerVEs, the fourth most frequent NP event in SLE, are usually attributable to lupus. In contrast to good physician reported outcomes, patients report a sustained reduction in health-related quality of life following CerVEs. This article is protected by copyright. All rights reserved.

Relationship Between Fish Consumption and Disease Activity in Rheumatoid Arthritis.

Abstract: Objective: To assess whether more frequent fish consumption is associated with lower RA disease activity scores among participants in an RA cohort. Methods: We conducted a cross-sectional analysis using baseline data from participants in the Evaluation of Subclinical Cardiovascular Disease and Predictors of Events in RA (ESCAPE-RA) cohort study. Frequency of fish consumption was assessed by a baseline food frequency questionnaire assessing usual diet in the past year. Multivariable, total energy-adjusted linear regression models provided effect estimates and 95% confidence intervals (CI) for frequency of fish consumption (never to <1/month, 1/month to <1/week, 1/week, and ≥2/week) on baseline DAS28-CRP. We also estimated the difference in DAS28-CRP associated with increasing fish consumption by one serving per week. Results: Among 176 participants, median DAS28-CRP was 3.5 (interquartile range 2.9-4.3). In an adjusted linear regression model, subjects consuming fish ≥2 times/week had a significantly lower DAS28-CRP compared with subjects who ate fish never to <1/month (difference -0.49 [95% CI -0.97, -0.02]). For each additional serving of fish per week, DAS28-CRP was significantly reduced by 0.18 (95% CI -0.35, -0.004). Conclusions: Our findings suggest that higher intake of fish may be associated with lower disease activity in RA patients. This article is protected by copyright. All rights reserved.