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Objective: To determine the risk of recurrent or new malignancy with exposure to targeted disease‐modifying antirheumatic drugs (DMARDs) in adults with rheumatoid arthritis (RA), axial spondyloarthritis (SpA), or psoriatic arthritis (PsA) and a history of cancer. Methods: We performed a systematic search of the literature for articles published up to June 2019 that investigated adults with RA, axial SpA, or PsA who had a history of cancer and received biologic or targeted synthetic DMARDs (bDMARDs or tsDMARDs). We compared the risk of relapse or occurrence of new cancer between patients with and without bDMARDs. Rate ratios (RRs) with 95% confidence intervals (95% CIs) were estimated. The heterogeneity of the studies was evaluated by the Cochran Q test and the I2 statistic. Results: We included 24 observational studies of chronic inflammatory arthritis; of those, 12 were included in the meta‐analysis of RA patients receiving bDMARDs. As compared with RA patients with a history of cancer and not receiving bDMARDs, for those receiving any bDMARD, the overall RR for risk of neoplasia was 1.09 (95% CI 0.92–1.32; P = 0.31, I2 = 8%); with tumor necrosis factor inhibitors, it was 1.11 (95% CI 0.85–1.46; P = 0.45, I2 = 48%); and with rituximab, it was 0.79 (95% CI 0.41–1.53; P = 0.49, I2 = 0%). The RR for risk of recurrence for skin cancer was 1.32 (95% CI 1.02–1.72; P = 0.04, I2 = 0%) and for breast neoplasia 1.21 (95% CI 0.84–1.72; P = 0.31, I2 = 0%). Conclusion: Apart from skin cancers including melanoma, the risk of recurrent or new cancer is not increased with the initiation of bDMARDs for RA as compared with no bDMARDs. [ABSTRACT FROM AUTHOR]

Objective: To determine whether patient global assessment of disease activity (PtGA) over the first year of disease course, as part of a Boolean-based definition of remission and considered individually, had a significant relationship with structural progression over 3 years in patients with early arthritis.Methods: We conducted a prospective, observational study using ESPOIR (Étude et Suivi des Polyarthrites Indifférenciées Récentes) cohort data. Remission states were defined as 1) 4-variable remission, which included a tender joint count in 28 joints, a swollen joint count in 28 joints (SJC28), a C-reactive protein (CRP; mg/dl) level, and PtGA (scored 0-10, all scores of ≤1); 2) PtGA near remission, which included the same parameters as 4-variable remission with only PtGA >1 (of a maximum possible score of 10); 3) 3-variable remission (sum of the proportion of patients in 4-variable remission and the proportion of patients in PtGA near remission); or 4) nonremission. The strictest status satisfied both at 6 and 12 months was considered. Radiographic progression was determined as a change of ≥5 points in the total Sharp/van der Heijde score (ΔSHS) from baseline to 3 years. The predictive capacities for radiographic damage of different remission definitions were assessed by odds ratio (OR). The association between each individual component of remission with ΔSHS was tested through multivariate linear regression analyses.Results: Among 520 patients, 7% achieved 4-variable remission and 12% achieved PtGA near remission. Radiographic progression was observed in 29% of patients who achieved 4-variable remission (OR versus nonremission; OR 0.32 [95% confidence interval (95% CI) 0.15, 0.68]) and in 45% of patients with PtGA near remission (OR 0.65 [95% CI 0.38, 1.11]); the comparison was not statistically different (OR 0.49 [95% CI 0.20, 1.18]). In 3-variable remission, radiographic progression was observed in 39%. Of the individual components, only the SJC28 and CRP level were associated with radiographic progression.Conclusion: All definitions of remission led to low structural degradation in early arthritis, and 4-variable remission led to less radiographic progression than PtGA near remission, but without a statistically significant difference. Both 4-variable remission and 3-variable remission appear to be useful targets when aiming for structural nonprogression. [ABSTRACT FROM AUTHOR]

Objective: To investigate determinants of the physician global assessment (PhGA) of disease activity and the influence of the contextual factors on this relationship in patients with early axial spondyloarthritis (SpA). Methods: Five‐year data of DESIR, a cohort of early axial SpA, were analyzed. Univariable generalized estimating equations (GEEs) were used to investigate contributory explanatory effects of various potential determinants of PhGA. Effect modification by contextual factors (age, sex, and educational level) was tested, and if significant, models were stratified. Autoregressive GEE models (i.e., models adjusted for PhGA at the previous time point) were used to confirm a longitudinal relationship. Results: A total of 708 patients were included. Higher Bath Ankylosing Spondylitis Disease Activity Index individual questions, swollen joint count in 28 joints (SJC28), tender joint count in 53 joints, Maastricht Ankylosing Spondylitis Enthesitis Score, C‐reactive protein (CRP) level, and Bath Ankylosing Spondylitis Metrology Index score were associated with a higher PhGA. Sex and age were effect modifiers of SJC28; the contributory effect of SJC28 was largest in the younger male stratum (β = 1.07 [95% confidence interval (95% CI) 0.71, 1.43]), and the smallest in the older female stratum (β = 0.13 [95% CI 0.04, 0.22]). Autoregressive GEE models revealed the same determinants as having a longitudinal association with PhGA and the same pattern of effect modification. Conclusion: Patients' subjective symptoms, peripheral arthritis and enthesitis, higher CRP level, and impaired spinal mobility contribute to explaining PhGA in patients with early axial SpA, irrespective of sex and age. Intriguingly, physicians consider the presence of swollen joints as more important in males than in females. [ABSTRACT FROM AUTHOR]

Objective: Hydroxychloroquine (HCQ) improves metabolic and cardiovascular outcomes in patients with rheumatoid arthritis (RA), but its efficacy appears to be moderate as compared to placebo. The aim of our study was to assess the current literature on the clinical and structural efficacy of HCQ in the joints of patients with RA.Methods: We systematically searched MEDLINE (via PubMed), Embase, Cochrane Library, and the American College of Rheumatology and European League Against Rheumatism annual scientific meeting abstracts for studies available up to November 2017 comparing the efficacy of HCQ in patients with RA, in monotherapy or combined with other conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Data were extracted by 1 investigator and independently checked by a different investigator.Results: The literature search revealed 197 articles and abstracts of potential interest, and 11 studies fulfilled inclusion criteria. The clinical and structural efficacy of HCQ was similar to or lower than that for methotrexate or sulfasalazine in monotherapy. HCQ combined with other DMARDs could increase the clinical efficacy.Conclusion: In addition to its metabolic benefit, combining HCQ with other DMARDs could provide some clinical improvement in patients with RA and inadequate response to previous csDMARDs. [ABSTRACT FROM AUTHOR]

Objective: Patients with immune-mediated inflammatory diseases such as rheumatoid arthritis or systemic lupus erythematosus are at increased risk of cardiovascular disease. However, the cardiovascular risk of patients with primary Sjögren's syndrome (SS) remains poorly studied. We aimed to investigate the association between primary SS and cardiovascular morbidity and mortality.Methods: We performed a systematic review of articles in Medline and the Cochrane Library and recent abstracts from US and European meetings, searching for reports of randomized controlled studies of cardiovascular morbidity and cardiovascular mortality in primary SS. The relative risk (RR) values for cardiovascular morbidity and mortality associated with primary SS were collected and pooled in a meta-analysis with a random-effects model by using Review Manager (Cochrane collaboration).Results: The literature search revealed 484 articles and abstracts of interest; 14 studies (67,124 patients with primary SS) were included in the meta-analysis. With primary SS versus control populations, the risk was significantly increased for coronary morbidity (RR 1.34 [95% confidence interval (95% CI) 1.06-1.38]; P = 0.01), cerebrovascular morbidity (RR 1.46 [95% CI 1.43-1.49]; P < 0.00001), heart failure rate (odds ratio 2.54 [95% CI 1.30-4.97]; P < 0.007), and thromboembolic morbidity (RR 1.78 [95% CI 1.41-2.25]; P < 0.00001), with no statistically significant increased risk of cardiovascular mortality (RR 1.48 [95% CI 0.77-2.85]; P = 0.24).Conclusion: This meta-analysis demonstrates that primary SS is associated with increased cardiovascular morbidity, which suggests that these patients should be screened for cardiovascular comorbidities and considered for preventive interventions, in a multidisciplinary approach with cardiologists. [ABSTRACT FROM AUTHOR]

Objective: To investigate the impact of baseline and time‐varying factors on the risk of serious adverse events (SAEs) in patients during long‐term certolizumab pegol (CZP) treatment. Methods: Safety data were pooled across 34 CZP clinical trials in rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), and plaque psoriasis (PSO). Cox proportional hazards modeling was used to investigate the association of baseline patient characteristics with risk of serious infectious events (SIEs), malignancies, and major adverse cardiac events (MACEs). Cox modeling for recurrent events assessed the impact of time‐varying body mass index (BMI), systemic corticosteroid (CS) use, and disease activity on SIE risk in RA and SAE risk in PSO. Results: Data were pooled from 8747 CZP‐treated patients across indications. Cox models reported a 44% increase in SIE risk associated with a baseline BMI of 35 kg/m2 or more versus a baseline BMI of 18.5 kg/m2 to less than 25 kg/m2. Baseline systemic CS use, age of 65 years or more, and disease duration of 10 years or longer also increased SIE risk. Older age was the only identified risk factor for malignancies. The risk of MACEs increased 107% for BMI of 35 kg/m2 or more versus BMI of 18.5 kg/m2 to less than 25 kg/m2 and increased 51% for men versus women. Higher disease activity, older age, systemic CS use, BMI of 35 kg/m2 or more, and baseline comorbidities were SIE risk factors in RA. Age and systemic CS use were risk factors for SAEs in PSO. Conclusion: Age, BMI, systemic CS use, and disease activity were identified as SIE risk factors in CZP‐treated patients. Risk of malignancies was greater in older patients, whereas obesity and male sex were MACE risk factors. [ABSTRACT FROM AUTHOR]

Objective: In rheumatoid arthritis, the association between advanced therapies (including biologic disease-modifying antirheumatic drugs [DMARDs] and targeted synthetic DMARDs) and methotrexate (MTX) is recommended by international societies. When MTX cannot be used, other conventional synthetic DMARDs (csDMARDs) may be proposed. We aimed to compare the safety and efficacy of MTX and non-MTX csDMARDs in combination with advanced therapies.Methods: We systematically searched the literature for studies comparing the effectiveness, retention rate, and safety of MTX versus non-MTX csDMARDs (leflunomide or others) in combination with tumor necrosis factor inhibitors (TNFi), abatacept, rituximab, tocilizumab, and JAK inhibitors. Meta-analysis was performed with RevMan, using an inverse variance approach with fixed or random-effects models. Risk ratios (RRs) and 95% confidence intervals (95% CIs) were estimated.Results: The literature search revealed 3,842 articles; 41 studies were included for the systematic literature review and 21 for the meta-analysis: 13 with TNFi, 3 with abatacept, and 5 with rituximab. For TNFi, the European Alliance of Associations for Rheumatology (EULAR) response at 6 months was lower for patients receiving non-MTX csDMARDs than for those using MTX (RR 0.93 [95% CI 0.87, 1.0], P = 0.04; n = 3,843; I2 = 28%), with a lower retention rate at 12 months. For abatacept, effectiveness and safety were similar between the 2 groups. For rituximab, a good EULAR response was higher with leflunomide than MTX (RR 1.38 [95% CI 1.13, 1.68], P = 0.001; n = 2,078; I2 = 0%), with similar adverse event rates. Meta-analysis for tocilizumab or JAK inhibitors could not be performed.Conclusion: The different csDMARDs seem safe and efficient to combine with advanced therapies in RA patients. Although MTX seems slightly superior to other csDMARDs in combination with TNFi, leflunomide might be superior to MTX in combination with rituximab. [ABSTRACT FROM AUTHOR]

Objective: To assess the prevalence and associations of renal dysfunction in patients with rheumatoid arthritis (RA).Methods: COMEDRA is a French nationwide cross-sectional multicenter study on comorbidities in RA. Renal function was assessed from the estimated glomerular filtration rate (eGFR), using the Modification of Diet in Renal Disease equation. RA characteristics and risk factors for renal impairment were collected. Two logistic regression models, 1 with and 1 without the Framingham Risk Score, were constructed from variables that were significantly associated with an eGFR of <60 ml/minute/1.73 m(2) or were clinically relevant.Results: Of the 970 recruited patients, 931 were analyzed (women 79.6%, mean age 57.8 years, disease duration 11.1 years, Disease Activity Score in 28 joints using the erythrocyte sedimentation rate [DAS28-ESR] 3.1). A total of 82 patients (8.8%) had an eGFR <60 ml/minute/1.73 m(2) and 9% had proteinuria. In univariate analysis, renal impairment was associated with age (P < 0.001), history of hypertension (P < 0.001), high systolic blood pressure (P = 0.03), and the Systematic Coronary Risk Evaluation (SCORE) equation (P = 0.002), but not with sex, disease duration, disease activity (as assessed by DAS28-ESR), nonsteroidal antiinflammatory drug use, disease severity (erosions, joint replacement), or RA medications. Multivariate analysis models showed that age (odds ratio [OR] 1.05 [95% confidence interval (95% CI) 1.03-1.09]) and hypertension (OR 2.5 [95% CI 1.5-4.3]) were associated with renal impairment. A second model showed that the SCORE equation (OR 1.33 [95% CI 1.06-1.67]) was associated with renal impairment.Conclusion: Renal impairment is relatively common in RA and is associated with cardiovascular risk factors such as age, hypertension, and the SCORE equation but not with disease activity or severity. [ABSTRACT FROM AUTHOR]

Glucocorticoids are widely used in rheumatoid arthritis (RA); however, their effectiveness and safety is still a subject of debate. In particular, when to introduce glucocorticoids, but also when and how to taper them, are important questions for clinicians. In this paper, we will discuss the place of glucocorticoids in the European League Against Rheumatism (EULAR) recommendations for the management of RA and review the literature that was the basis for these recommendations. The recommendations cover the introduction of glucocorticoids (and for whom they are recommended), doses and duration of treatment, and tapering strategies. Items still on the research agenda include more data on safety, particularly for long-term use, and small doses of glucocorticoids. [ABSTRACT FROM AUTHOR]

Objective Many outcomes have been proposed in the assessment of psoriatic arthritis (PsA). The Outcome Measures in Rheumatology (OMERACT) core set for PsA evaluation comprises 6 domains: joints, skin, function, pain, patient's global assessment, and quality of life. The objective of this work was to assess reporting of outcomes in PsA, including patient-reported outcomes (PROs) in recent publications. Methods A systematic literature search of clinical trials related to PsA and reporting at least 1 clinical outcome between 2006 and 2010 was performed in PubMed, i.e., just before to just after publication of the OMERACT core set. All clinical outcomes were noted and subdivided into domains of health. Data analysis was descriptive. Results Fifty-eight articles (12,405 patients) were included in the analysis: 17 (29%) were randomized clinical trials; the patients' mean ± SD age was 48.2 ± 5.4 years and the mean ± SD disease duration was 9.0 ± 3.1 years. Eighty-four different outcomes were reported, with a mean ± SD of 6.9 ± 4.3 per study. Patients were mainly assessed using the 6 core set domains, reported in 37.9% (quality of life) to 55.2% (skin) of articles; however, the core set was rarely completely reported since only 10.3% of the studies reported all 6 core domains. PROs were heterogeneous and in particular there was no consensus regarding the number of joints to assess and instruments for dactylitis and enthesitis. PROs were assessed in more than 75% of publications using 28 different instruments. Conclusion There is great heterogeneity in PsA assessment, even since publication of the OMERACT core set. Better consensus on instruments to assess each domain of health and better insight into which outcomes are important for patients is needed. [ABSTRACT FROM AUTHOR]

A letter is presented in response to the article "Similar effects of disease-modifying antirheumatic drugs, glucocorticoids, and biologic agents on radiographic progression in rheumatoid arthritis: meta-analysis of 70 randomized placebo-controlled or drug- controlled studies, including 112 comparisons" by Dr. N. Graudal and G. Jürgens in the October 2010 issue.