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 s 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 s 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.
Cardiovascular disease (CVD) is the leading cause of mortality in patients with rheumatoid arthritis (RA). Hydroxychloroquine (HCQ) has been shown to improve survival rates in other inflammatory ...diseases. We aimed to assess the available literature on the cardiovascular impact of HCQ in patients with RA.
We systematically searched for studies evaluating the effects of HCQ on cardiovascular outcomes of known risk factors for CVD in patients with RA. Databases searched were MEDLINE (via PubMed), EMBase, Cochrane Library and the American College of Rheumatology and European League Against Rheumatism annual meetings. A meta-analysis was performed with a random-effects model, estimating mean differences (MDs), HRs and 95% CIs. Data were extracted by one investigator and independently checked by another.
The literature search revealed 185 articles and abstracts of interest; further examination resulted in 16 studies fulfilling the criteria. The MDs between HCQ users and non-users in levels of total, low-density and high-density cholesterol and triglycerides were -9.8 (95% CI -14.0 to -5.6), -10.6 (95% CI -14.2 to -7.0), +4.1 (95% CI 2.2 to 6.0) and -19.2 (95% CI -27.2 to -11.1), respectively. Diabetes incidence was lower for HCQ ever users than never users (HR 0.59 (95% CI 0.49 to 0.70)). HCQ seemed to decrease insulin resistance and incidence of CVD, but data were too few for meta-analysis.
Besides its limited efficacy for disease activity and progression, HCQ may benefit the metabolic profile and to a lesser extent cardiovascular events in patients with RA, which suggests its usefulness combined with other conventional synthetic disease-modifying antirheumatic drugs.
To update the evidence for the safety of synthetic disease-modifying antirheumatic drugs (sDMARDs), glucocorticoids (GC) and biological DMARDs (bDMARDs) in patients with rheumatoid arthritis (RA) to ...inform the European League Against Rheumatism (EULAR) recommendations for the management of RA.
Systematic literature review (SLR) of observational studies (including registries). Interventions were any bDMARD (anakinra, infliximab, etanercept, adalimumab, rituximab, abatacept, tocilizumab, golimumab or certolizumab pegol) or sDMARD (methotrexate, leflunomide, hydroxychloroquine, sulfasalazine, gold/auranofin, azathioprine, chlorambucil, chloroquine, cyclosporin, cyclophosphamide, mycophenolate, minocycline, penicillamine, tacrolimus or tofacitinib) and a comparator was required. Information on GCs was collected from the included studies. All safety outcomes were included.
Forty-nine observational studies addressing diverse safety outcomes of therapy with bDMARDs met eligibility criteria. Substantial heterogeneity precluded meta-analysis of any of the outcomes. Patients on tumour necrosis factor inhibitors (TNFi) compared to patients on conventional sDMARDs had a higher risk of serious infections (adjusted HR (aHR) 1.1-1.8), a higher risk of tuberculosis, and an increased risk of infection by herpes zoster cannot be excluded. Patients on TNFi did not have an increased risk for malignancies in general, lymphoma or non-melanoma skin cancer, but the risk of melanoma may be slightly increased (aHR 1.5). From the studies identified on conventional sDMARDs, no new safety signals were found.
The findings from this SLR confirm the known safety pattern of sDMARDs and bDMARDs for the treatment of RA.
In this article, the 2010 European League against Rheumatism (EULAR) recommendations for the management of rheumatoid arthritis (RA) with synthetic and biological disease-modifying antirheumatic ...drugs (sDMARDs and bDMARDs, respectively) have been updated. The 2013 update has been developed by an international task force, which based its decisions mostly on evidence from three systematic literature reviews (one each on sDMARDs, including glucocorticoids, bDMARDs and safety aspects of DMARD therapy); treatment strategies were also covered by the searches. The evidence presented was discussed and summarised by the experts in the course of a consensus finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) were determined. Fourteen recommendations were developed (instead of 15 in 2010). Some of the 2010 recommendations were deleted, and others were amended or split. The recommendations cover general aspects, such as attainment of remission or low disease activity using a treat-to-target approach, and the need for shared decision-making between rheumatologists and patients. The more specific items relate to starting DMARD therapy using a conventional sDMARD (csDMARD) strategy in combination with glucocorticoids, followed by the addition of a bDMARD or another csDMARD strategy (after stratification by presence or absence of adverse risk factors) if the treatment target is not reached within 6 months (or improvement not seen at 3 months). Tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, biosimilars), abatacept, tocilizumab and, under certain circumstances, rituximab are essentially considered to have similar efficacy and safety. If the first bDMARD strategy fails, any other bDMARD may be used. The recommendations also address tofacitinib as a targeted sDMARD (tsDMARD), which is recommended, where licensed, after use of at least one bDMARD. Biosimilars are also addressed. These recommendations are intended to inform rheumatologists, patients, national rheumatology societies and other stakeholders about EULAR's most recent consensus on the management of RA with sDMARDs, glucocorticoids and bDMARDs. They are based on evidence and expert opinion and intended to improve outcome in patients with RA.
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.
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 m2 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 m2 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.
To update a previous systematic review assessing the efficacy of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in rheumatoid arthritis (RA).
Two systematic reviews of the ...literature using PubMed, Embase and the Cochrane library were performed from 2009 until January 2013 to assess the efficacy of csDMARDs (as monotherapy or combination therapy) in adults with RA, and the efficacy of glucocorticoids in early RA. A third systematic review was performed until March 2013 to assess the efficacy of tofacitinib by meta-analysis.
For glucocorticoids, of 222 hits, five publications relating to four new trials were analysed for efficacy, confirming that initial treatment of RA with low-dose prednisone plus methotrexate (MTX) results in better clinical and structural outcomes at 1 and 2 years than treatment with MTX alone. For csDMARDs, of 498 studies, only two new studies were randomised controlled trials comparing MTX monotherapy with MTX in combination with another csDMARD without differences in glucocorticoid usage. Using tight control principles, clinical outcomes were no better with immediate triple therapy than with 'step-up' therapy. For tofacitinib, the pooled analysis of 10 trials showed that tofacitinib was more efficacious on signs and symptoms, disability and appeared to be more efficacious on structural damage than control treatment with placebo (OR (95% CI)--American College of Rheumatology 20% (ACR20) response: 2.44 (1.97 to 3.02)) or treatment with MTX (ACR20 response: 2.38 (1.66 to 3.43)).
Addition of low-dose glucocorticoids to csDMARD therapy produces benefits in early RA. Under tight control conditions, combination therapy with csDMARDs is no better than MTX monotherapy. Tofacitinib is a new DMARD with proven efficacy.
Although methotrexate (MTX) is the consensual first-line disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis (RA), substantial heterogeneity remains with its prescription and ...dosage, which are often not optimal.
To evaluate the symptomatic and structural impact of optimal MTX dose in patients with early RA in daily clinical practice over 2 years.
Patients included in the early arthritis ESPOIR cohort who fulfilled the ACR-EULAR (American College of Rheumatology/European League against Rheumatism) criteria for RA and received MTX as a first DMARD were assessed. Optimal MTX dose was defined as ≥10 mg/week during the first 3 months, with escalation to ≥20 mg/week or 0.3 mg/kg/week at 6 months without Disease Activity Score in 28 joints remission. Symptomatic and structural efficacy with and without optimal MTX dose was assessed by generalised logistic regression with adjustment for appropriate variables.
Within the first year of follow-up, 314 patients (53%) with RA received MTX as a first DMARD (mean dose 12.2±3.8 mg/week). Only 26.4% (n=76) had optimal MTX dose. After adjustment, optimal versus non-optimal MTX dose was more efficient in achieving ACR-EULAR remission at 1 year (OR 4.28 (95% CI 1.86 to 9.86)) and normal functioning (Health Assessment Questionnaire ≤0.5; OR at 1 year 4.36 (95% CI 2.03 to 9.39)), with no effect on radiological progression. Results were similar during the second year.
Optimal MTX dose is more efficacious than non-optimal dose for remission and function in early arthritis in daily practice, with no impact on radiological progression over 2 years.
Abstract Introduction This article reports the latest recommendations of the French Society for Rheumatology (SFR) regarding the management of rheumatoid arthritis (RA). Methods New recommendations ...were developed by hospital- and community-based rheumatologists having extensive experience with RA and a patient self-help organization representative. They rest on the recently issued EULAR recommendations and a literature review. Results Points emphasized in the 15 recommendations include the need to share treatment decisions between the rheumatologist and the patient, the acquisition by patients of self-management skills, remission or minimal disease activity as the treatment target, the need for initiating disease-modifying drugs as early as possible, and the usefulness of regular disease activity assessments to allow rapid treatment adjustments if needed (i.e., tight disease control). First-line methotrexate monotherapy is recommended, with concomitant short-term glucocorticoid therapy if indicated by the risk/benefit ratio. Patients who fail this approach (no response after 3 months or target not achieved after 6 months) can be considered for another synthetic disease-modifying antirheumatic drug (DMARD: leflunomide or sulfasalazine), combined synthetic DMARD therapy, or methotrexate plus a biologic, depending on the prognostic factors and patient characteristics. If the first biologic fails, switching to a second biologic is recommended. In the event of a sustained remission, cautious dosage reduction of the biological and/after synthetic DMARDs is in order. Conclusion These recommendations are designed to improve the management of patients with RA.
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 s 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 s 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.
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