Comparable Rates of Glucocorticoid‐Associated Adverse Events in Patients With Polymyalgia Rheumatica and Comorbidities in the General Population

Objective

To investigate the use of glucocorticoids (GCs) and related adverse events (AEs) in a long‐term, geographically defined cohort of patients with polymyalgia rheumatica (PMR).

Methods

Using a population‐based inception cohort, details of GC therapy were abstracted from medical records of all patients diagnosed with PMR in 2000–2014. Age‐ and sex‐matched comparators without PMR were identified from the same underlying population. Cumulative and daily dosage of GC, rate of disease relapse, occurrence of GC‐related AEs, and rate of GC discontinuation were analyzed.

Results

The study included 359 patients with PMR and 359 comparators. The median time to taper below 5 mg/day for 6 months was 1.44 years (95% confidence interval [95% CI] 1.36–1.62), while the median time to permanent discontinuation was 5.95 years (95% CI 3.37–8.88). The mean ± SD cumulative dose of GC at 2 and 5 years was 4.0 ± 3.5 grams and 6.3 ± 9.8 grams, respectively. The mean ± SD daily dose of GC at 2 and 5 years was 6.1 ± 7.6 mg/day and 7.2 ± 9.5 mg/day, respectively. There were no differences in rates of AEs between patients with PMR and comparators for diabetes mellitus, hypertension, hyperlipidemia, or hip, vertebral, or Colles fractures (P > 0.2 for all). Cataracts were more common in patients with PMR than comparators (hazard ratio 1.72 [95% CI 1.23–2.41]).

Conclusion

Relapse rates in PMR are highest in the early stages of therapy. Despite often protracted therapy, with the exception of cataracts, the rates of studied morbidities linked to GC are not more common in PMR than comparators.

     

Differentiating Psoriatic Arthritis From Psoriasis Without Psoriatic Arthritis Using Novel Serum Biomarkers

Objective

There is a high prevalence of undiagnosed psoriatic arthritis (PsA) in patients with psoriasis. Identifying soluble biomarkers for PsA will help in screening psoriasis patients for appropriate rheumatology referral. We therefore aimed to investigate whether serum levels of novel markers previously discovered by quantitative mass spectrometric analysis of synovial fluid and skin biopsies performs better than the C‐reactive protein (CRP) level in differentiating PsA patients from those with psoriasis without PsA (PsC).

Methods

In this case–control study, serum samples were obtained from 100 subjects with PsA, 100 with PsC, and 100 healthy controls. Patients with PsA and PsC were group matched for age, sex, psoriasis duration, and Psoriasis Area and Severity Index and were not currently receiving biologic treatment. Using enzyme‐linked immunosorbent assay, 4 high‐priority markers (Mac‐2‐binding protein [M2BP], CD5‐like protein [CD5L], myeloperoxidase [MPO], and integrin β5 [ITGβ5]), as well as previously established markers (matrix metalloproteinase 3 [MMP‐3] and CRP level) were assayed. Data were analyzed using logistic regression. Receiver operating characteristic (ROC) curves were plotted.

Results

In comparisons to controls, CD5L, ITGβ5, M2BP, MPO, MMP‐3, and CRP level were independently associated with PsA, while only CD5L, M2BP, and MPO were independently associated with PsC alone. In comparisons to PsC, ITGβ5, M2BP, and CRP level were independently associated with PsA. ROC analysis of this model shows an area under the curve (AUC) of 0.85 (95% confidence interval [95% CI] 0.80–0.90). The model that included CRP level alone had an AUC of 0.71 (95% CI 0.64–0.78).

Conclusion

CD5L, ITGβ5, M2BP, MPO, MMP‐3, and CRP level are markers for PsA. The combination of ITGβ5, M2BP, and CRP level differentiates PsA from PsC, and performs better than CRP level alone.

     

Incident Spine Surgery in Patients With Ankylosing Spondylitis: A Secondary Cohort Analysis of a Nationwide,Population‐Based Health Claims Database

Objective

To evaluate the risk of the need for spine surgery, including cervical and lumbar spine surgeries in patients with ankylosing spondylitis (AS), compared with those without the disease.

Methods

A secondary data analysis was conducted using population‐based claims data from the Taiwan National Health Insurance Research Database. Adult patients with newly diagnosed AS between January 2000 and December 2012 were identified based on the International Classification of Diseases, Ninth Revision, Clinical Modification code 720.0. A comparison cohort was assembled using frequency‐matched sex, 10‐year age intervals, and index year with the AS cohort at a ratio of 5:1. All patients were followed until our study outcomes (any spine surgery, cervical spine surgery, and lumbar spine surgery), based on surgical codes, had occurred, or until the end of the followup period. Incidence rate ratios (IRRs) were calculated using Poisson regression models.

Results

We identified 3,462 patients with AS and 17,310 patients without AS. All 3 outcome variables were seen at a significantly higher incidence in the AS cohort than in the comparison cohort (IRR 2.34 [95% confidence interval (95% CI) 1.92–2.87] for any spine surgery, IRR 2.36 [95% CI 1.55–3.59] for cervical spine surgery, and IRR 2.33 [95% CI 1.85–2.93] for lumbar spine surgery). Moreover, the magnitudes of the IRRs were the largest in the youngest age group (individuals in their 20s and 30s).

Conclusion

Patients with AS, particularly those in their 20s and 30s, had a significantly higher risk of needing any spine surgery, cervical spine surgery, and lumbar spine surgery, compared with patients without AS.

     

Trial Characteristics as Contextual Factors When Evaluating Targeted Therapies in Patients With Psoriatic Disease: A Meta‐Epidemiologic Study

Objective

To assess the importance of trial characteristics as contextual factors when evaluating the treatment effect of targeted therapies for patients with psoriatic disease.

Methods

We identified randomized controlled trials (RCTs) evaluating targeted therapies approved for psoriatic arthritis (PsA) and psoriasis (8 biologics and apremilast). The effect of targeted therapies was analyzed in the 2 psoriatic conditions combined by using drug retention as a common outcome, and separately by using the American College of Rheumatology 20% improvement criteria (ACR20) for PsA and the Psoriasis Area Severity Index 75% improvement score (PASI75) for psoriasis. We explored potential effect modification of trial characteristics in stratified and meta‐regression analyses. Odds ratios (ORs) were calculated and compared among the trial eligibility criteria via the ratio of ORs.

Results

Forty‐eight PsA and psoriasis trials (51 comparisons; 17,737 patients) were eligible. Overall retention was OR 2.16 (95% confidence interval [95% CI] 1.70–2.75) with higher odds for PsA trials compared with psoriasis trials (ratio of ORs 2.55 [95% CI 1.64–3.97]). The eligibility criteria “targeted therapy history,” “minimum required disease duration,” “required negative rheumatoid factor,” and “required Classification Criteria for Psoriatic Arthritis criteria” were of importance for achieving ACR20 in PsA. The eligibility criterion “minimum required disease duration” was of importance for achieving PASI75 in psoriasis. A total of 7 PsA trials had rescue before time‐point‐of‐retention reporting (adaptive trials).

Conclusion

From this exploratory meta‐epidemiologic study, we now have evidence from RCTs to support the notion that patients with PsA are more likely to adhere to targeted therapies compared to patients with psoriasis. Furthermore, we identified a few contextual factors of importance in regard to achieving ACR20 in PsA trials and PASI75 in psoriasis trials.

     

Association of Comorbidities in Spondyloarthritis With Poor Function,Work Disability,and Quality of Life: Results From the Assessment of SpondyloArthritis International Society Comorbidities in Spondyloarthritis Study

Objective

Comorbidities add to the burden of disease and its complexity, and may prevent the achievement of treat‐to‐target goals. The objective of this study was to study the relationship between comorbidities and key disease outcomes in spondyloarthritis (SpA), namely function, work ability, and quality of life.

Methods

Patients from the multinational (22 countries), cross‐sectional Assessment in SpondyloArthritis international Society (ASAS) Comorbidities in Spondyloarthritis study were included in the analysis, provided they fulfilled the ASAS criteria. Data on comorbidities based on both self‐ and physician‐report were collected through questionnaires and were subsequently used to compute the Rheumatic Disease Comorbidity Index (RDCI). Univariable and multivariable (adjusted for relevant confounders) multilevel (with country as a random effect) linear or logistic (as appropriate) regression analyses were conducted to investigate the relationship between the RDCI and functional ability, work ability, and quality of life.

Results

In total, 3,370 of 3,984 recruited patients (85%) fulfilled the ASAS criteria: 66% were male, mean ± SD age was 43 ± 14 years, mean ± SD disease duration was 8.4 ± 9.5 years, and mean ± SD RDCI was 0.7 ± 1.1. At least 1 comorbidity was reported in 51% of patients; 9% had ≥3 comorbidities. RDCI was independently associated with a higher Bath Ankylosing Spondylitis Functional Index score (β = 0.37, 95% confidence interval [95% CI] 0.30, 0.43), lower EuroQol 5‐domain questionnaire (β = ?0.03, 95% CI ?0.04, ?0.02), less work employment (odds ratio [OR] 0.83, 95% CI 0.76, 0.91), higher absenteeism (OR 1.18, 95% CI 1.04, 1.34), and higher presenteeism (OR 1.42, 95% CI 1.26, 1.61).

Conclusion

Comorbidities in SpA adversely influence physical function, work ability, and quality of life and are important to take into account in daily clinical practice.

     

Medical Care Costs Associated With Rheumatoid Arthritis in the US: A Systematic Literature Review and Meta‐Analysis

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.

     

Profiling Response to Tumor Necrosis Factor Inhibitor Treatment in Axial Spondyloarthritis

Objective

Lack of response to tumor necrosis factor inhibitor (TNFi) agents is not uncommon, encountered during the treatment of axial spondyloarthritis (SpA) patients, and it can be classified as primary lack of response (PLR) or secondary lack of response (SLR). The primary aim of this study was to evaluate factors associated with TNFi failure types and their characteristics in axial SpA.

Methods

Adult axial SpA patients who were TNFi naive at the time of baseline evaluation and started receiving their first biologics for active axial disease were identified. Based on the clinical response to the first TNFi, patients were then stratified into 3 groups: PLR, SLR, and responders. Clinical, demographic, and laboratory data were collected and analyzed.

Results

There was a total of 249 axial SpA patients in the study (70.7% male, mean ± SD age 37.3 ± 12.4 years), which included PLR (n = 62), SLR (n = 93), and responders (n = 94). PLR patients tended to be older, with a lower HLA–B27 rate, a higher percentage of nonresponder axial SpA patients, and a higher baseline Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score compared to SLR patients or responders. In multiple regression analysis, increasing age, negative HLA–B27, higher baseline BASDAI, and treatment with the soluble TNF receptor protein were the independent predictors of PLR.

Conclusion

PLR accounted for nearly 40% of the TNFi failures in axial SpA patients. Older age, negative HLA–B27, higher baseline disease activity, and treatment with soluble TNF receptors were the independent predictors of the primary nonresponse to TNFi.

     

Risk of Hepatitis B Virus Reactivation in Patients With Inflammatory Arthritis Receiving Disease‐Modifying Antirheumatic Drugs: A Systematic Review and Meta‐Analysis

Objective

To assess hepatitis B virus (HBV) reactivation rates in patients with resolved or chronic HBV infection, receiving disease‐modifying antirheumatic drugs (DMARDs) and with or without antiviral prophylaxis.

Methods

We conducted a systematic review and meta‐analysis. Electronic searches were conducted in PubMed, Medline, and Embase using Ovid through December 31, 2015. A search strategy was developed for each database using the following inclusion criteria: for participants, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and resolved or chronic HBV infection; for intervention, tumor necrosis factor (TNF) inhibitors or non‐TNF biologic or nonbiologic DMARDs; and for outcome, HBV reactivation. Four reviewers independently extracted study data and assessed study quality using the Newcastle‐Ottawa Scale. To determine the pooled HBV reactivation rate, the variances of the raw proportions were stabilized using a Freeman‐Tukey‐type arcsine square root transformation, using a random‐effects model.

Results

Twenty‐five studies met the inclusion criteria. The overall pooled rate of HBV reactivation was 1.6% (95% confidence interval [95% CI] 0.8–2.6) in patients with resolved HBV. Similar rates were observed in resolved patients taking TNF inhibitors (1.4% [95% CI 0.5–2.6]), non‐TNF biologics (6.1% [95% CI 0.0–16.6]), and nonbiologic DMARDs (1.7% [95% CI 0.2–4.2]). We also found that the reactivation rate was lower in patients with chronic HBV infection who received antiviral prophylaxis (9.0% [95% CI 4.1–15.5]) than in those who did not (14.6% [95% CI 4.3–29.0]).

Conclusion

We found that the HBV reactivation rate in inflammatory arthritis patients receiving DMARDs was low in resolved patients and moderate in patients with chronic HBV infection. Further, lower rates were observed in patients with chronic HBV infection who were using antiviral prophylaxis.

     

Impact of Disease Severity,Illness Beliefs,and Coping Strategies on Outcomes in Psoriatic Arthritis

Objective

Little is known about how people with psoriatic arthritis (PsA) cope with and manage their condition, but data show that psychological problems are underrecognized and undertreated. The Common Sense Self‐Regulatory Model (CS‐SRM) suggests illness beliefs, mediated by coping, may influence health outcomes. The study aimed to investigate the roles of disease severity, illness beliefs, and coping strategies in predicting depression, anxiety, and quality of life (QoL) in people with PsA. Additionally, we aimed to assess the role of depression and anxiety in predicting QoL.

Methods

We conducted a cross‐sectional observational study, where adults with PsA (n = 179) completed validated measures of predictor (illness beliefs, coping strategies, disease severity) and outcome variables (depression, anxiety, QoL) using an online survey distributed via social media.

Results

The participants were a community sample of 179 adults with PsA, ages 20 to 72 years (77.1% female). After controlling for disease severity, hierarchical multiple regression models indicated that more negative beliefs about consequences and behavioral disengagement as a coping method predicted levels of depression, and self‐blame predicted anxiety. Beliefs about consequences and the presence of depression predicted quality of life scores after controlling for disease severity.

Conclusion

This study offers support for the use of the CS‐SRM in explaining variation on psychological outcomes in individuals with PsA. The illness beliefs and coping strategies identified as predictors in this article are potential targets for interventions addressing PsA‐related distress and QoL.

     

Relationship Between Fish Consumption and Disease Activity in Rheumatoid Arthritis

Objective

To assess whether more frequent fish consumption is associated with lower rheumatoid arthritis (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 Rheumatoid Arthritis 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 (95% CIs) for frequency of fish consumption (i.e., never to <1 time/month, 1 time/month to <1 time/week, 1 time/week, and ≥2 times/week) on baseline Disease Activity Score in 28 joints (DAS28) using the C‐reactive protein (CRP) level. We also estimated the difference in DAS28‐CRP associated with increasing fish consumption by 1 serving per week.

Results

Among 176 participants, the median DAS28‐CRP score 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 time/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).

Conclusion

Our findings suggest that higher intake of fish may be associated with lower disease activity in RA patients.

     

Patterns of Systemic Treatment for Psoriatic Arthritis in the US: 2004–2015

Objective

To examine trends in the use of systemic disease‐modifying antirheumatic drugs (DMARDs) among patients with psoriatic arthritis (PsA) in the US.

Methods

Using claims data (2004–2015) from a large US commercial health plan, we identified patients with PsA who initiated DMARD therapy. We examined baseline patient characteristics and initial treatment patterns. We then assessed changes in the DMARD regimen over the 12‐month period after the first DMARD initiation date. Using Poisson regression, we estimated age‐ and sex‐adjusted incidence rates of treatment changes in each calendar year.

Results

We identified 9,222 PsA patients who initiated DMARD therapy (42.8% biologic DMARDs [bDMARDs] and 57.2% conventional synthetic DMARDs [csDMARDs]). Initiators of bDMARDs were younger than those initiating csDMARDs (mean ± SD age 48 ± 13 versus 52 ± 14 years) and generally had fewer comorbidities, but a higher proportion of bDMARD initiators received nonsystemic treatments for psoriasis at baseline. Methotrexate was the most frequently used DMARD, constituting 80.6% of csDMARD initiations. Etanercept (49.1%) was the most commonly prescribed bDMARD, followed by adalimumab (34.4%). During the 12‐month followup after the first DMARD initiation, 20.1% of bDMARD initiators and 31.1% of csDMARD initiators had their initial DMARD regimen modified, with an increasing trend in treatment modifications over the 11‐year study period (P = 0.03). Overall, 5.3% of patients discontinued treatment, but the rates of discontinuation decreased over time (P < 0.001).

Conclusion

In this large cohort of PsA patients with DMARD initiation, more than 40% were treated with a bDMARD. We found an increasing trend in treatment modification after use of the initial DMARD and a decreasing trend in complete DMARD discontinuation over the past decade.

     

Treating Early Undifferentiated Arthritis: A Systematic Review and Meta‐Analysis of Direct and Indirect Trial Evidence

Objective

We undertook a systematic review and meta‐analysis of direct and indirect trial evidence to evaluate the efficacy of treatments for patients with undifferentiated arthritis (UA).

Methods

We searched 4 electronic databases from inception to January 2016, clinicaltrials.gov, and bibliographies of relevant articles. Two reviewers independently screened and evaluated the studies. The primary outcome was development of rheumatoid arthritis (RA).

Results

Nine studies were included. Interventions included methotrexate, abatacept, infliximab, intraarticular or intramuscular glucocorticoids, and radiation synovectomy. Treating patients resulted in lower rates of RA at 12 months compared to placebo or no treatment (odds ratio [OR] 0.49 [95% confidence interval (95% CI) 0.26, 0.90]). From direct meta‐analysis, patients treated with methotrexate were less likely to develop RA at 12 months compared to patients treated without methotrexate (OR 0.13 [95% CI 0.03, 0.48]). This difference was no longer significant at 30 or 60 months. From indirect comparisons, most interventions showed decreased risk of developing RA compared to placebo at 12 months, reaching statistical significance for methotrexate (OR 0.16 [95% CI 0.08, 0.33]) and intramuscular methylprednisolone (OR 0.72 [95% CI 0.53, 0.99]). Most individual interventions included a limited number of studies.

Conclusion

Treating patients with UA resulted in a statistically significant delay in the development of RA, with the largest effect observed for methotrexate. These findings suggest that there is a window of opportunity to treat patients with UA early, to delay subsequent progression to RA.

     

Perioperative Timing of Infliximab and the Risk of Serious Infection After Elective Hip and Knee Arthroplasty

Objective

The optimal timing of tumor necrosis factor antagonists before elective surgery is unknown. This study evaluated the association between infliximab timing and serious infection after elective hip or knee arthroplasty.

Methods

A retrospective cohort study evaluated US Medicare patients with rheumatoid arthritis, inflammatory bowel disease, psoriasis, psoriatic arthritis, or ankylosing spondylitis who received infliximab within 6 months of elective knee or hip arthroplasty from 2007 to 2013. Propensity‐adjusted analyses examined whether infliximab stop timing (time between the most recent infusion and surgery) was associated with hospitalized infection within 30 days or prosthetic joint infection (PJI ) within 1 year.

Results

Hospitalized infection within 30 days occurred after 270 of 4,288 surgeries (6.3%). Infliximab stop timing <4 weeks versus 8–12 weeks was not associated with an increase in infection within 30 days (propensity‐adjusted odds ratio [OR ] 0.90 [95% confidence interval (95% CI ) 0.60–1.34]). The rate of PJI was 2.9 per 100 person‐years and was not increased in patients with stop timing <4 weeks versus 8–12 weeks (hazard ratio [HR ] 0.98 [95% CI 0.52–1.87]). Glucocorticoid dosage >10 mg/day was associated with increased risk of 30‐day infection (OR 2.11 [95% CI 1.30–3.40]) and PJI (HR 2.70 [95% CI 1.30–5.60]). Other risk factors for infection included elderly age, comorbidities, revision surgery, and previous hospitalized infection.

Conclusion

Administering infliximab within 4 weeks of elective knee or hip arthroplasty was not associated with a higher risk of short‐ or long‐term serious infection compared to withholding infliximab for longer time periods. Glucocorticoid use, especially >10 mg/day, was associated with an increased infection risk.

     

Association Between Dose of Glucocorticoids and Coronary Artery Lesions in Kawasaki Disease

Objective

Several studies revealed the efficacy of glucocorticoids on prevention of coronary artery lesions (CALs) in Kawasaki disease (KD) patients. However, impacts of different doses of glucocorticoids on clinical outcomes of KD remain unknown.

Methods

Using the Japanese Diagnosis Procedure Combination inpatient database, we evaluated KD patients who were treated with normal‐dose (prednisolone 0.5–4.0 mg/kg/day) or high‐dose (methylprednisolone 10–40 mg/kg/day) glucocorticoids. We investigated risks of CALs and readmission, total hospitalization cost, and length of hospital stay in the acute phase of KD using propensity score matching, stabilized propensity‐score inverse probability of treatment weighting, and instrumental variable methods.

Results

We identified a total of 3,220 patients with KD who were treated with normal‐dose (n = 2,453) or high‐dose (n = 767) glucocorticoids in addition to intravenous immunoglobulin. One‐to‐one propensity‐matched analyses with 744 pairs demonstrated no significant differences between the normal‐dose and the high‐dose groups in risk of CALs (risk ratio [RR] 0.83, 95% confidence interval [95% CI] 0.49, 1.40) and risk of readmissions (RR 0.85, 95% CI 0.65, 1.11). Stabilized propensity‐score inverse probability weighting and instrumental variable analyses showed similar results to the propensity score matching analyses.

Conclusion

Risks of CALs and readmissions and total hospitalization costs were similar between the normal‐dose and the high‐dose glucocorticoids groups for patients with KD, whereas total length of hospital stay was shorter in the high‐dose group than that in the normal‐dose group.

     

Overweight,Obesity, and the Likelihood of Achieving Sustained Remission in Early Rheumatoid Arthritis: Results From a Multicenter Prospective Cohort Study

Objective

Obesity is implicated in rheumatoid arthritis (RA) development, severity, outcomes, and treatment response. We estimated the independent effects of overweight and obesity on ability to achieve sustained remission (sREM) in the 3 years following RA diagnosis.

Methods

Data were from the Canadian Early Arthritis Cohort, a multicenter observational trial of early RA patients treated by rheumatologists using guideline‐based care. sREM was defined as Disease Activity Score in 28 joints (DAS28) <2.6 for 2 consecutive visits. Patients were stratified by body mass index (BMI) as healthy (18.5–24.9 kg/m²), overweight (25–29.9 kg/m²), and obese (≥30 kg/m²). Cox regression was used to estimate the effect of the BMI category on the probability of achieving sREM over the first 3 years, controlling for age, sex, race, education, RA duration, smoking status, comorbidities, baseline DAS28, Health Assessment Questionnaire disability index, C‐reactive protein level, and initial treatment.

Results

Of 982 patients, 315 (32%) had a healthy BMI, 343 (35%) were overweight, and 324 (33%) were obese; 355 (36%) achieved sREM within 3 years. Initial treatment did not differ by BMI category. Compared to healthy BMI, overweight patients (hazard ratio [HR] 0.75 [95% confidence interval (95% CI) 0.58–0.98]) and obese patients (HR 0.53 [95% CI 0.39–0.71]) were significantly less likely to achieve sREM.

Conclusion

Rates of overweight and obesity were high (69%) in this early RA cohort. Overweight patients were 25% less likely, and obese patients were 47% less likely, to achieve sREM in the first 3 years, despite similar initial disease‐modifying antirheumatic drug treatment and subsequent biologic use. This is the largest study demonstrating the negative impact of excess weight on RA disease activity and supports a call to action to better identify and address this risk in RA patients.

     

Effect of Fatigue,Older Age,Higher Body Mass Index,and Female Sex on Disability in Early Rheumatoid Arthritis in the Treatment‐to‐Target Era

Objective

To compare disease activity and disability over 2 years in early rheumatoid arthritis (RA) before and after implementation of treat‐to‐target therapy and identify predictors of adverse outcome.

Methods

The Yorkshire Early Arthritis Register (YEAR) recruited 725 patients with early RA between 2002 and 2009, treated with a step‐up approach. The Inflammatory Arthritis Continuum study (IACON) recruited cases between 2010 and 2014 and treated to target. A total of 384 IACON cases met 2010 American College of Rheumatology/European League Against Rheumatism criteria. Latent growth curves of change in Disease Activity Score in 28 joints (DAS28) and the Health Assessment Questionnaire (HAQ) were compared between YEAR and IACON. Latent class growth analysis identified trajectories of change. Baseline predictors of trajectories were identified using logistic regression.

Results

The mean DAS28 over 2 years was lower in IACON than in YEAR. Latent trajectories of HAQ change in YEAR were high stable (21% of cohort), moderate reducing (35%), and low reducing (44%). Only moderate reducing (66%) and low reducing (34%) were seen in IACON. In both cohorts, female sex and fatigue predicted adverse HAQ trajectories (high stable and moderate reducing). Odds ratios (ORs) for moderate reducing compared to low reducing for women were 2.58 (95% confidence interval [95% CI] 1.69, 4.49) in YEAR and 5.81 (95% CI 2.44, 14.29) in IACON. ORs per centimeter fatigue visual analog score were 1.13 (95% CI 1.07, 1.20) in YEAR and 1.16 (95% CI 1.12, 1.20) in IACON.

Conclusion

Treat‐to‐target therapy gave more favorable trajectories of change in DAS28 and HAQ, but adverse HAQ trajectory was more likely in women with greater fatigue, suggesting such patients would benefit from interventions to improve function as well as reduce inflammation.

     

Prevalence and Disease‐Specific Risk Factors for Lower Urinary Tract Symptoms in Systemic Sclerosis: An International Multicenter Study

Objective

To determine the prevalence of lower urinary tract symptoms (LUTS) in systemic sclerosis (SSc), to find specific risk factors, and to assess their impact on quality of life (QoL).

Methods

In a multicenter study, 334 patients completed a self‐administered questionnaire on LUTS and QoL. LUTS were classified into 3 main categories: storage, voiding, and post‐micturition symptoms. Digestive symptoms burden was captured by a visual analog scale, divided into 5 equal categories. Multivariable logistic regressions were performed to test association between risk factors and LUTS categories. Linear regression adjusted the association between LUTS and QoL.

Results

LUTS were recorded in 311 SSc patients (96.0%) and classified as severe in 120 (38.0%). The storage category of LUTS was the most prevalent (91.9%), followed by voiding (72.2%) and then by post‐micturition symptoms (49.8%). Risk factors identified in the multivariable models were higher than the median Health Assessment Questionnaire disability index (HAQ DI; odds ratio [OR] 4.2 [95% confidence interval (95% CI) 1.4–12.9]) in the storage category; higher than the median HAQ DI (OR 2.4 [95% CI 1.2–4.9]) for digestive symptoms burden (OR 1.9 [95% CI 1.3–2.7]) and synovitis (OR 4.8 [95% CI 1.0–22.6) in the voiding category; and higher for digestive symptoms burden (OR 1.2 [95% CI 1.0–1.5]) in the post‐micturition category of symptoms. These factors also increased the odds of having further severe symptoms. QoL was affected by the 3 categories of LUTS and decreased progressively with increasing frequency of symptoms.

Conclusion

Self‐reported LUTS are among the most frequent symptoms in SSc and are associated with digestive symptoms. SSc patients with LUTS have lower QoL.

     

Dyslipidemia,Alcohol Consumption,and Obesity as Main Factors Associated With Poor Control of Urate Levels in Patients Receiving Urate‐Lowering Therapy

Objective

In real life, in a substantial proportion of gouty patients receiving urate‐lowering therapy (ULT), urate levels are not maintained below the target of 6.0 mg/dl. We aimed to search for factors associated with poor control of serum uric acid (UA) levels in a large population of patients with gout receiving ULT.

Methods

This cross‐sectional study involved adults with gout in primary care who were receiving ULT. Demographics, gout history, comorbidities, lifestyle, clinical factors, concomitant treatments, and laboratory data were compared in well‐controlled gout (serum UA ≤6.0 mg/dl) versus poorly controlled gout (serum UA >6.0 mg/dl) on univariate and multivariate analyses.

Results

Among the 1,995 patients receiving ULT, only 445 (22.3%) had reached the target of 6.0 mg/dl serum UA. Such patients had a lower rate of gout flares within the previous year than patients without the target (mean ± SD 1.7 ± 1.4 versus 2.1 ± 1.4; P < 0.0001). The main factors associated with poor serum UA level control in multivariate analysis were low high‐density lipoprotein cholesterol level (adjusted odds ratio [OR] 0.5 [95% confidence interval (95% CI) 0.26–0.96]; P = 0.04), high total cholesterol level (OR 1.83 [95% CI 1.29–2.60]; P = 0.0007), increased waist circumference (OR 1.55 [95% CI 1.11–2.13]; P = 0.008), and alcohol consumption (OR 1.52 [95% CI 1.15–2.00]; P = 0.003).

Conclusion

Dyslipidemia, abdominal obesity, and alcohol consumption are the main factors associated with a poor response to ULT. Knowledge of these factors might help physicians identify cases of gout that may be less likely to achieve target urate level.

     

Mortality in Patients With Giant Cell Arteritis: A Cohort Study in UK Primary Care

Objective

To examine whether giant cell arteritis (GCA) is associated with increased all‐cause mortality and whether mortality differs according to age, sex, and calendar year of cohort entry.

Methods

Using the UK‐based Clinical Practice Research Datalink, we identified 9,778 newly diagnosed GCA patients from 1990–2014, and up to 10 nonvasculitis patients randomly matched to each case on age, sex, practice, and years of history before cohort entry. We used Cox regression to estimate adjusted hazard ratios (HRs) for mortality of GCA patients in comparison to nonvasculitis patients, then stratified by age, sex, and calendar year of cohort entry.

Results

Compared with nonvasculitis patients, GCA patients had increased mortality during the first year following diagnosis (adjusted HR 1.51, 95% confidence interval [95% CI] 1.40–1.64), and marginally increased mortality between 1 and 5 years after the diagnosis (adjusted HR 1.16, 95% CI 1.09–1.23), but not >5 years after the diagnosis (adjusted HR 1.06, 95% CI 1.00–1.12). GCA patients diagnosed before age 65 years had the highest mortality risk during the first year following diagnosis (adjusted HR 2.32, 95% CI 1.60–3.35). The mortality risk did not differ substantially by sex or calendar year of cohort entry.

Conclusion

GCA patients had an increased risk of mortality during the period shortly after the GCA diagnosis, in particular during the first year, but no increased risk after 5 years postdiagnosis. The mortality risk differed by age with an even greater increased 1‐year mortality in those age <65 years at diagnosis, but not by sex or calendar year of cohort entry.