Factors Associated with Sustained Remission in Rheumatoid Arthritis in Patients Treated with Anti-Tumour Necrosis Factor (anti-TNF)


Objectives. Anti-tumour necrosis factor antibody (anti-TNF) has revolutionised the treatment of rheumatoid arthritis (RA) and remission is now a realistic possibility for patients. Despite widespread use of anti-TNFs, predicting which patients are most likely to attain a sustained good response to these treatments remains challenging. Our objective was to undertake a systematic review of the literature to evaluate existing evidence for demographic and clinical factors associated with the achievement of sustained remission in individuals with RA treated with anti-TNF.

Methods. EMBASE, MEDLINE and the Cochrane Controlled Trials Register were searched along with studies identified from reference lists. Quality of studies was assessed using Newcastle-Ottawa criteria. Meta-analysis was undertaken where unadjusted odds ratios were available for the same demographic or clinical factors from at least three studies.

Results. Six studies were identified. Concomitant methotrexate use was associated with an increased likelihood of achieving sustained remission. Greater baseline disease activity, tender joint count, age, disease duration, baseline functional impairment and female gender were associated with reduced likelihood of achieving sustained remission.

Conclusions. Factors predicting sustained remission are seldom reported. Evidence identified in this review supports current recommendations for methotrexate co-prescription and highlights the negative impact of particular clinical and demographic features on the likelihood of achieving optimal response to anti-TNF treatment. Sustained remission is clinically more relevant than point remission in RA. More widespread reporting of sustained remission will help clinicians set realistic expectations on likely long-term treatment efficacy and could be an important tool for identifying patients suitable for dose optimisation. This article is protected by copyright. All rights reserved.

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Comorbidities in patients with Primary Sjögren’s Syndrome and Systemic Lupus Erythematosus: A comparative registries-based study


Objective: To compare the prevalence of the main comorbidities in two large cohorts of patients with Primary Sjögren’s Syndrome (pSS) and Systemic Lupus Erythematosus (SLE), with focus on cardiovascular (CV) diseases.

Methods: Cross-sectional multicenter study where the prevalence of more relevant comorbidities in two cohorts was compared. Patients under follow-up from the SJOGRENSER (Spanish Rheumatology Society Register of pSS) and RELESSER (Spanish Rheumatology Society Register of SLE) registries, and who fulfilled the 2002-AECG and 1997-ACR classification criteria, respectively, were included. A binomial logistic regression analysis was carried out to explore potential differences, making general adjustments for age, sex and disease duration and specific adjustments for each variable, including CV risk factors and treatments, when it was judged appropriate.

Results: A total of 437 pSS patients (95% female) and 2,926 SLE patients (89% female) were included. Mean age: 58.6 (p55-p75: 50.0-69.9) and 45.1 years (36.4-56.3), respectively (p<0.001). Disease duration: 10.4 (6.0-16.7) and 13.0 years (7.45-19.76), respectively (p<0.001). Smoking, dyslipidemia and arterial hypertension were associated less frequently with pSS [OR: 0.36 (95%CI:0.28-0.48), OR: 0.74 (0.58-0.94) and OR: 0.50 (0.38-0.66), respectively] as were life-threatening CV events (i.e., stroke or myocardial infarction) [OR: 0.57 (0.35-0.92)]. Conversely, lymphoma was associated more frequently with pSS [OR 4.41 (1.35-14.43)]. The prevalence of severe infection was lower in pSS than in SLE (10.1% vs 16.9%, p<0.001; OR: 0.54 (0.39-0.76).

Conclusions: pSS patients have consistently less serious CV comorbidity burden and a lower prevalence of severe infection than those with SLE. In contrast, their risk of lymphoma was greater. This article is protected by copyright. All rights reserved.

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Secular changes in clinical features at presentation of rheumatoid arthritis: Increase in comorbidity but improved inflammatory states


Objective: To examine secular trends in demographic, clinical manifestations and comorbidity on first presentation of RA prior to DMARD treatment.

Methods: 2701 patients were recruited over 25years to two UK-based RA inception cohorts: the Early RA Study (9 centres; 1986-2001) and the Early RA Network (23 centres; 2002-2012). Trends in demographic and baseline clinical/laboratory and radiographic variables and comorbidities were estimated using mixed effects models, including random effects for recruitment centre.

Results: Age-at-onset increased from 53.2 to 57.7 years in 1990 and 2010 respectively (2.6 months/year; 95% CI 1.2-4.1). Gender-ratio, the proportion living in deprived areas and smoking status were unchanged (p>0.05) and there were no changes in the proportion seropositive or erosive at baseline (p>0.05). After controlling for treatment at the time of assessment, ESR reduced and haemoglobin increased over time (p<0.05), however HAQ, DAS, DAS28, and joint counts were unchanged (p>0.05). The overall prevalence of comorbidity increased from 29.0% in 1990 to 50.7% in 2010, mainly due to cardiovascular and non-cardiac vascular conditions including hypertension. There was a significant increase in BMI (0.15 units/year; 95% CI 0.11-0.18), resulting in an increase in the prevalence of obesity from 13.3% in 1990 to 33.6% in 2010.

Conclusions: Age-at-onset and comorbidity burden, especially obesity have increased at RA presentation over 25 years, reflecting wider demographic trends at the population level. In contrast there were no accompanying changes in disease severity assessed by composite markers of disease activity, radiographic erosions, seropositivity or HAQ at presentation. Treatment strategies in early RA should take greater account of the impact of co-morbidity on outcomes. This article is protected by copyright. All rights reserved.

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Efficacy of tailored exercise therapy on physical functioning in patients with knee osteoarthritis and comorbidity: A randomized controlled trial


Objective. To evaluate the efficacy on physical functioning and safety of tailored exercise therapy in patients with knee osteoarthritis (KOA) and comorbidities.

Method. In a randomized controlled trial, 126 participants were included with a clinical diagnosis of KOA and at least one of the following target comorbidities: coronary disease, heart failure, type 2 diabetes, chronic obstructive pulmonary disease or obesity (body mass index≥ 30kg/m2), with severity score ≥2 on the Cumulative Illness Rating Scale. The intervention group received a 20-week, individualized, comorbidity-adapted exercise program consisting of aerobic and strength training. The control group received their current medical care for KOA and were placed on a waiting list for exercise therapy. Primary outcome measures were Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) subscale physical functioning and 6-minute walking test (6-MWT). Measurements were performed at baseline, after 20 weeks (post-treatment) and at 3 months post-treatment.

Results. Statistically significant physical functioning differences over time were found between the intervention and control group (WOMAC;B= -7.43, 95%CI -9.99 to -4.87, p<0.001 and 6-MWT; B= 34.16, 95%CI 17.68 to 50.64, p<0.001) in favor of the intervention group. At 3-months follow, the mean improvements in the intervention group were 33% on the WOMAC scale and 15% on the 6-MWT. These improvements are of clinical relevance. No serious adverse events occurred during the intervention.

Conclusion. This is the first study showing that tailored exercise therapy is efficacious in improving physical functioning and safe in patients with KOA and severe comorbidities. This article is protected by copyright. All rights reserved.

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Trends in Gout and Rheumatoid Arthritis Hospitalizations in Canada from 2000-2011


Objective: Gout and rheumatoid arthritis (RA) are the two most common forms of inflammatory arthritis worldwide. As hospitalizations for both conditions lead to substantial health resource use, contemporary inpatient trends and associated costs may provide important benchmarks of disease burden. However, relevant data are limited.

Methods: We used PopulationData BC, a population-based administrative dataset from Canada. We examined trends in the annual hospitalization and surgery rate of gout and RA from 2000-2011. We additionally examined annual trends in the inpatient cost burden of both conditions. We assessed annual trends in hospitalization and surgery rates using Poisson regression models and cost trends using linear regression models.

Results: From 2000 to 2011, the annual hospitalization rate for RA declined by 49% from 15.4 to 7.9 per 100,000 Canadian adults (p<0.001), whereas that for gout doubled from 3.8 to 7.6 per 100,000 Canadian adults (p<0.001). Approximately 31% of RA admissions were associated with hip or knee replacement surgery; the trend of these surgeries paralleled the declining trend in RA hospitalizations (p=0.0097). The inpatient costs also reflected the hospitalization trends, with a 40% decrease in RA hospital costs, while gout costs more than doubled over the study period.

Conclusion: Our findings indicate that hospitalization rates for gout have doubled over the past decade, while those for RA have decreased considerably. While these data provide an encouraging benchmark for RA care, they also highlight the critical need to improve gout management and prevention to mitigate its rising disease burden in Canada and beyond. This article is protected by copyright. All rights reserved.

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Exercise in takayasu arteritis: Effects on inflammatory and angiogenic factors and disease-related symptoms


Objective: To investigate the effects of acute and chronic exercise in female patients with remissive Takayasu arteritis (TA). Methods: This was a two-part prospective study. In study 1, cytokines and soluble TNF receptors were assessed at rest and every 60 minutes during a 3-hour recovery period following an acute exercise session in TA (n=11) and heathy control (HC, n=10). In study 2, a sub-sample from TA group (n=6) underwent a 12-week exercise training program. Before and after training, the acute session of aerobic exercise was performed and cytokines and soluble TNF receptors were assessed at the same time-points described above. Muscle function, strength, aerobic capacity, endothelial function, quality of life, and walking impairment scores were evaluated. Results: In study 1, the acute session of aerobic exercise led to overall similar responses on cytokine kinetics in TA and HC groups. In study 2, the exercise training program did not exacerbate inflammatory cytokines in TA patients, whilst the pro-inflammatory cytokine TNF-α was diminished both at resting and following the acute session of aerobic exercise. In addition, the exercise training program increased the pro-angiogenic factors VEGF (at resting) and PDGF AA (at resting and in response to the acute session of aerobic exercise. The exercise training program improved muscle strength and function, whereas aerobic capacity, quality of life, and endothelial function parameters remained unchanged. Conclusion: Exercise could be a well-tolerable, safe and efficient intervention able to induce immunomodulatory and pro-angiogenic effects and to increase strength and function in patients with TA. This article is protected by copyright. All rights reserved.

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Validation of international classification of disease codes for the epidemiological study of dermatomyositis


Objective: To assess the validity of using ICD-9-CM code 710.3 to identify adult patients with dermatomyositis in outpatient and inpatient settings.

Methods: Electronic medical records were examined for adult patients with ICD-9 code 710.3 between January 2001 and November 2014 (n=511). Physician diagnosis, clinical findings and diagnostic testing results were recorded. A dermatomyositis rating scale was assigned based on classic cutaneous findings and at least 2 additional clinical and diagnostic findings from the Bohan criteria. Sensitivity and positive predictive values (PPV) were determined. Sensitivity analyses were performed to evaluate the accuracy of multiple ICD-9 codes in the outpatient setting, as well as primary and secondary inpatient codes.

Results: The sensitivity and PPV for multiple ICD-9 codes of 710.3 in the outpatient setting was 0.89 and 0.35, respectively. The PPV for primary and secondary inpatient codes of 710.3 was 0.95 and as high as 0.8. However, the sensitivity of ICD-9 code 710.3 was poor in the inpatient setting (primary: 0.23; secondary: 0.26). Miscoding as diabetes mellitus (32%) was the most common reason for failure to meet appropriate dermatomyositis criteria followed by diagnosis at an outside institution (19%), dermatomyositis as a rule out diagnosis (10%), cutaneous dermatomyositis (8%), and juvenile dermatomyositis (6%).

Conclusion: One or more occurrences of ICD-9 code 710.3 are insufficient to support diagnosis of dermatomyositis in the outpatient setting. However, ICD-9 codes of 710.3 appear to be valid in the inpatient setting. This article is protected by copyright. All rights reserved.

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External validation of the Lupus Impact Tracker in a longitudinal cohort with systemic lupus erythematosus from the Southeastern United States


We examined the external validity of the Lupus Impact Tracker (LIT), a systemic lupus erythematosus (SLE)-specific, health related quality of life (HRQOL) tool in a population-based cohort of patients with SLE in Atlanta, Georgia, United States. We modeled the association of LIT scores with patient-reported measures of SLE activity (Systemic Lupus Activity Questionnaire (SLAQ)) and organ damage (Self- administered Brief Index of Lupus Damage (SA-BILD)). We investigated the association of LIT scores with general HRQOL using the Short-Form 12 (SF-12).

Correlation, multivariable regression, and longitudinal analyses using general linesar modeling with fixed effects were performed to investigate the association between the LIT and 1) patient-reported disease activity (SLAQ); 2) patient-reported disease damage (SA-BILD); 3) Mental Component Summary (MCS) of the SF-12; and 4) Physical Component Summary (PCS) of the SF-12. Demographic trends related to the LIT were also assessed using cross-sectional analysis.

The LIT was significantly associated with the disease activity (SLAQ), organ damage (SA-BILD), MCS, and PCS in both adjusted and unadjusted regression analysis (p < 0.0001). Longitudinal analysis demonstrated significant association between LIT and disease activity (SLAQ), MCS, and PCS (p < 0.0001), but not organ damage (SA-BILD).

The LIT is a simple, patient-centered tool that can be used to assess HRQOL among patients with SLE. This study provides external validity of the LIT in a population-based cohort with a large number of African Americans with relatively high disease burden. This article is protected by copyright. All rights reserved.

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RAPID3 and ACR/EULAR Provisional Remission Definitions as Predictors of Radiographic Outcome in a Rheumatoid Arthritis Clinical Trial With Tocilizumab


Objective. The American College of Rheumatology/European League Against Rheumatism established definitions of remission for rheumatoid arthritis (RA) based on composite scores including tender and swollen joint counts (TJC/SJC), Patient Global visual analog scale (VAS) score, laboratory tests, and, in Simplified Disease Activity Index (SDAI), Physician Global score. Time constraints on a physician’s schedule demand an easy yet accurate tool to measure disease activity. We assessed the predictability of Routine Assessment of Patient Index Data 3 (RAPID3) with/without a single swollen joint versus SDAI and/or Boolean remission criteria for functional and radiographic outcomes.

Methods. Data were from the tociLIzumab Safety and THE Prevention of Structural Joint Damage (LITHE) phase 3 trial in RA patients. The ability, at year 1, of RAPID3 ≤3 + 1 SJC, RAPID3 ≤3 (remission) without SJC, SDAI ≤3.3 (remission) and/or Boolean remission (SJC,TJC, Patient Global VAS, and C-reactive protein [mg/dL] all ≤1) to predict year 2 Health Assessment Questionnaire–Disability Index (HAQ-DI) score ≤0.5 (normal), no worsening of HAQ-DI score from year 1, and no worsening of Genant-modified Total Sharp Score from year 1 was assessed.

Results. Among 690 patients, mean (SD) baseline Disease Activity Score at 28 joints (DAS28) was 6.5 (0.96), RAPID3 score was 14.2 (5.51), and SDAI score was 41.7 (13.01). Achieving year 1 measures was associated with good functional and radiographic outcomes at year 2. Sensitivity/specificity/positive predictive values/negative predictive values were 49.1%/83.2%/37.4%/88.9% (RAPID3 remission), 26.4%/91.7%/36.8%/87.1% (RAPID3 + 1SJC), 26.7%/90.9%/37.3%/85.9% (SDAI remission), and 17.0%/96.6%/47.4%/86.4% (Boolean remission).

Conclusion. The predictability of RAPID3 (with or without joint count) was similar to that of SDAI and Boolean criteria. This article is protected by copyright. All rights reserved.

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