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Objective: To report the 5-year outcome of a large prospective cohort of patients with very early rheumatoid arthritis (RA), and to identify factors predictive of outcome., Methods: Patients were recruited if they had early arthritis of < 6 months' duration, had a high probability of developing RA, and had never been prescribed disease-modifying antirheumatic drugs (DMARD) or steroids. Logistic regression analysis was used to determine factors that predict outcome., Results: We included 813 patients from December 2002 to April 2005. Age was 48.1 ± 12.6 years, delay before referral 103.1 ± 52.4 days, 28-joint Disease Activity Score (DAS28) 5.1 ± 1.3, Health Assessment Questionnaire (HAQ) 1.0 ± 0.7; 45.8% and 38.7% had rheumatoid factor or antibodies to cyclic citrullinated peptide (anti-CCP), respectively; 22% had hand or foot erosions; 78.5% fulfilled the American College of Rheumatology/European League Against Rheumatism criteria for RA at baseline and 93.8% during followup. At 5 years, 573 patients were evaluated. The outcome was mild for most patients: disease activity (median DAS28 = 2.5) and HAQ disability (median 0.3) were well controlled over time; 50.6% achieved DAS28 remission and 64.7% low disease activity. Radiographic progression was low (2.9 Sharp unit/year) and only a few patients required joint surgery. Nevertheless, some patients developed new comorbidities. During the 5 years, 82.7% of patients had received at least 1 DMARD (methotrexate, 65.9%), 18.3% a biological DMARD, and about 60% prednisone at least once. Anti-CCP was the best predictor of remaining in the cohort for 5 years, of prescription of synthetic or biologic DMARD, and of radiographic progression., Conclusion: The 5-year outcome of an early RA cohort in the 2000s was described. Anti-CCP was a robust predictor of outcome. The generally good 5-year outcome could be related to early referral and early effective treatment, key processes in the management of early RA in daily practice.

Our aim was to compare all eight biologics available for rheumatoid arthritis in two patient populations, methotrexate-naive patients and inadequate responders to methotrexate, based on a comprehensive literature review. The five TNFα antagonists, rituximab, abatacept and tocilizumab used with methotrexate were compared to methotrexate monotherapy using the ACR50 response as the primary clinical endpoint and absence of radiographic progression after 1 year as the primary radiological endpoint. Odds ratios (ORs) were computed, as well as the number needed to treat (NNT) to obtain an ACR50 response for each biologic. We included 22 studies. Overall, combined biologic therapy was significantly more effective than methotrexate alone in both the naive group (OR: 2.11; 95% confidence interval [95%CI], 1.85-2.41) and the unresponsive group (OR: 4.82; 95%CI: 3.83, 6.08). Crude NNTs were as follows: etanercept, five in the naive group and three in the unresponsive group; adalimumab, seven and three; infliximab, seven and five; abatacept, seven and four; rituximab, five and five; and tocilizumab and certolizumab, four in the unresponsive group. None of the differences was statistically significant. In the naive group, combined biologic therapy was associated with a higher rate of absence of radiographic progression after 1 year compared to methotrexate alone (OR: 2.19; 95%CI: 1.55-3.08). All biologics had approximately the same efficacy. Methotrexate-naive patients treated with biologics had significantly less radiographic progression than those with cellular therapy., (Copyright © 2012 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Objective: To describe the means of optimizing methotrexate therapy for rheumatoid arthritis in daily clinical practice, based on a systematic literature review., Methods: We systematically reviewed the literature by searching the PubMed, Embase, and Cochrane databases and reviewing communications to ACR and EULAR meetings for studies on methotrexate starting dosages, dosage increment sizes and intervals, maximum dosages, and routes of administration in patients with rheumatoid arthritis. We used an appropriate scoring system to assess the methodological quality of each selected study., Results: We identified 519 studies of which 11 were selected based on the titles and abstracts then on the full-length articles. Methotrexate was optimally effective when started in a high dosage (more than 10mg/week orally) that was subsequently increased by 5mg/month up to 25-30mg/week,(1) with appropriate adjustments based on clinical disease activity and tolerance of each patient. For a given methotrexate dosage, parenteral administration was more effective and produced fewer gastrointestinal adverse effects than oral administration., Conclusion: The information supplied by this systematic review support higher starting dosage, an intensive dosage increase schedule and recourse to parenteral administration in case of unresponsiveness or intolerance to oral methotrexate. They should improve the management of patients given methotrexate therapy for rheumatoid arthritis., (Copyright © 2011. Published by Elsevier SAS.)

Background & Aims: Although methotrexate (MTX) is used in the effective treatment of inflammatory disorders, its use is hampered by the risk of liver fibrosis. Non-invasive methods for the diagnosis of liver fibrosis, such as transient elastography (FibroScan) and FibroTest could be useful for monitoring MTX-liver toxicity. The aim of this case-control study was to determine factors associated with liver fibrosis in a large cohort of patients requiring MTX., Methods: Consecutive adults with various benign inflammatory diseases were prospectively assessed using FibroScan and FibroTest when they were treated with MTX (cases) or before beginning treatment (controls)., Results: Among 518 included patients, 44 patients (8.5%) had FibroScan and/or FibroTest results suggesting severe liver fibrosis. In a multivariate analysis, factors associated with abnormal markers of liver fibrosis were the body mass index >28 kg/m(2) and high alcohol consumption. Neither long MTX duration nor cumulative doses were associated with elevated FibroScan or FibroTest results., Conclusions: Severe liver fibrosis is a rare event in patients treated with MTX and is probably unrelated to the total dose. Patients with other risk factors for liver disease should be closely monitored with non-invasive methods before and during MTX treatment., (Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Objectives: In early and active RA despite MTX, continuous treatment with TNF blockers in combination with MTX is recommended. To compare this strategy with an initial combination of MTX and adalimumab (ADA) given for 3 months and then adjusted based on the disease activity status., Methods: Prospective unblinded randomized multicentre controlled 1-year trial in which 65 patients with early (<6 months) and active [disease activity score (DAS28(ESR)) >5.1] RA were assigned to Group 1 (32 patients): MTX (0.3 mg/kg/week, maximum of 20 mg/week, without escalating dose regimen) or to Group 2 (33 patients): initial combination therapy with MTX (as in Group 1) and ADA (40 mg eow). In both groups, treatment was adjusted every 3 months. The aim was to achieve a low DAS (DAS28(ESR) <3.2)., Results: From Week 12 until Week 52, seven patients in Group 1 and 11 patients in Group 2 remained in low disease activity state while receiving MTX monotherapy (P = 0.28). The 1-year area under the curve (AUC) of DAS28 was lower in Group 2 owing to an initial better response. The total intake of anti-TNF-alpha and the mean increase in total modified Sharp score was similar in the two groups., Conclusions: Initial combination of MTX and ADA and then an adjusted based on the disease activity status achieved a faster control of disease activity but did not increase the number of patients for whom anti-TNF-alpha treatment was not needed after 12 weeks nor a better subsequent clinical or radiological outcome than a 3-month delayed initiation of anti-TNF in patients with still active disease despite MTX.

Objectives: To develop clinical practice guidelines for the use of methotrexate in rheumatoid arthritis (RA), using the evidence-based approach and expert opinion., Methods: A scientific committee used a Delphi procedure to select five questions, which formed the basis for developing recommendations. Evidence providing answers to the five questions was sought in the Cochrane databases, PubMed, and proceedings of meetings of the French Society for Rheumatology, European League Against Rheumatism, and American College of Rheumatology. Using this evidence, a group of rheumatologists developed and validated the recommendations. For each recommendation, the level of evidence and the extent of agreement among experts were specified., Results: The recommendations were as follows: 1: The starting dosage for methotrexate in patients with RA should not be less than 10 mg/week and should be determined based on disease severity and patient-related factors; 2: When a patient with RA shows an inadequate response to methotrexate, the dosage should be increased at intervals of 6 weeks, up to 20 mg/week, according to tolerance and patient-related factors; 3: When starting methotrexate treatment in a patient with RA, preference should be given to the oral route. A switch to the intramuscular or subcutaneous route should be considered in patients with poor compliance, inadequate effectiveness, or gastrointestinal side effects; 4: At present, there is no evidence indicating that a change in methotrexate dosage is in order when a TNF antagonist is given concomitantly; 5: The investigations that are mandatory before starting methotrexate therapy in a patient with RA consist of a full blood cell count, serum transaminase levels, serum creatinine with computation of creatinine clearance, and a chest radiograph. In addition, serological tests for the hepatitis viruses B and C and a serum albumin assay are recommended. In patients with a history of respiratory disease or current respiratory symptoms, lung function tests with determination of the diffusing capacity for carbon monoxide are recommended; 6: Investigations that are mandatory for monitoring methotrexate therapy in patients with RA consist of full blood cell counts and serum transaminase and creatinine assays. These tests should be obtained at least once a month for the first 3 months then every 4-12 weeks; 7: Folate supplementation can be given routinely to patients treated with methotrexate for RA. In practice, a minimal dosage of 5 mg of folic acid once a week, at a distance from the methotrexate dose, is appropriate; 8: In the event of respiratory symptoms possibly related to methotrexate toxicity, the drug must be stopped and symptom severity evaluated. Should evidence of serious disease be found, the patient should be admitted immediately or advice from a pulmonologist should be obtained immediately., Conclusion: Recommendations about methotrexate therapy for RA were developed. These recommendations should help to improve practice uniformity and, ultimately, to improve the management of RA.

Anti-drug antibodies (ADAbs) develop in up to a third of patients treated with biologic agents, with such immunogenicity being one of the main reasons for the loss of efficacy observed in an important proportion of patients treated with such agents. The appearance of ADAbs has consequences in terms of efficacy and tolerance of the biodrug: the development of ADAbs is associated with a poorer clinical response and with an increased risk of adverse effects. Formation of ADAbs has been observed with all biologic DMARDs, but anti-TNF agent mAbs appear to be the largest contributors, independent of humanization of the antibody. ADAb identification is technically difficult and not standardized, partly explaining important variations between published studies. A variety of factors can influence the risk of ADAb appearance, some of which are linked to the treatment strategy, such as the combination with synthetic DMARDs or the rhythm of administration of the biodrug, whereas other factors are dependent on the patient, such as the level of inflammation at onset or body weight. The detection of these antibodies and/or the dosage of the biologic agent itself could have consequences for the bedside practice of clinicians and should be well understood. This review of the literature proposes an overview of the data published on the subject to help clinicians manage the biodrugs according to these new concepts. [ABSTRACT FROM AUTHOR]

Résumé: Notre but a été de comparer les huit biothérapies disponibles pour le traitement de la polyarthrite rhumatoïde dans deux populations différentes de patients, les patients naïfs au méthotrexate et ceux ayant eu une réponse inadéquate au méthotrexate, en se basant sur une revue extensive de la littérature. Les cinq anti-TNFα, le rituximab, l’abatacept et le tocilizumab utilisés en association au méthotrexate ont été comparés au méthotrexate en monothérapie en utilisant la réponse ACR50 comme objectif primaire ainsi que l’absence de progression structurale à 1 an de la première évaluation radiographique. Les odds ratios (OR) ont été calculés de même que le nombre de sujets nécessaires de traiter (Number Needed to Treat [NNT]) afin d’obtenir une réponse ACR50 pour chaque biothérapie. Nous avons inclus 22 études. Au total, l’association d’une biothérapie était significativement plus efficace que le méthotrexate seul, que ce soit dans le groupe des patients naïfs au méthotrexate (OR, 2,11 ; indice de confiance 95 % (IC95 %), 1,85–2,41) ou dans le groupe de réponse inadéquate au méthotrexate (OR, 4,82 ; IC95 %, 3,83–6,08). Les NNT bruts étaient les suivants : etanercept, cinq dans le groupe naïf et trois dans le groupe de réponse inadéquate ; adalimumab, sept et trois ; infliximab, sept et cinq ; abatacept, sept et quatre ; rituximab, cinq et cinq ; et tocilizumab et certolizumab, quatre dans le groupe réponse inadéquate. Aucune différence significative n’a été notée entre les biothérapies. Dans le groupe naïf, le traitement combiné était associé à une plus grande fréquence de l’absence de progression structurale après un an comparé au méthotrexate seul (OR, 2,19 ; IC95 %, 1,55–3,08). Toutes les biothérapies avaient approximativement la même efficacité. Les patients naïfs de méthotrexate traités par biothérapie avaient significativement moins de progression radiographique que ceux sous méthotrexate. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To develop recommendations about treatment (except anti-TNF agents) of psoriatic arthritis with peripheral joint involvement (PsA) seen in everyday practice, using evidence from the literature, supplemented with expert opinion when needed. Methods: The recommendations were based on evidence from the literature. First, a scientific committee used a Delphi procedure to select five focal points of interest. Then, a literature task force looked for relevant publications in the following: Cochrane, Pubmed, and Ovid databases and abstracts from the French Society for Rheumatology, European League against Rheumatism and American College of Rheumatology. Based on the data from these publications, recommendations were drafted and then validated by a group of 68 experts. The strength of each recommendation was determined, as well as the extent of agreement among the experts. Results: The evidence extracted from 73 selected papers was presented to experts during interactive workshops. At the end of the workshops, the experts drafted six recommendations, which were then validated by a final vote including all participants. These six recommendations displayed various strength from B to D. Conclusion: These recommendations should help to improve practice uniformity and, ultimately, to improve the management of PsA in France. [Copyright &y& Elsevier]

Résumé: Objectif: Proposer des recommandations sur la prise en charge thérapeutique (hors biothérapies) de patients souffrant de rhumatisme psoriasique périphérique en pratique quotidienne, selon la méthodologie de la médecine fondée sur les preuves (Evidence Based Medicine – EBM) et l’opinion d’experts. Méthodes: [•] Détermination de 5 questions, base de la rédaction des recommandations, par un comité scientifique selon la méthode Delphi. [•] Recherche d’éléments de réponse type EBM par une revue de la littérature. [•] Développement de recommandations par un comité d’experts à partir de ces éléments bibliographiques. Résultats: 1- Les cinq questions ont été sélectionnées sur les mesures thérapeutiques et les traitements de fond (hors biothérapie) au cours du rhumatisme psoriasique. Question n° 1 : Quelle est l’efficacité des AINS et des corticoïdes par voie générale dans le rhumatisme psoriasique ? Question n° 2 : Quels sont les traitements de fond (hors biothérapie) utiles pour contrôler les manifestations articulaires cliniques et les lésions structurales d’un rhumatisme psoriasique ? Question n° 3 : En quoi le psoriasis modifie-t-il le choix et la surveillance des traitements ? Question n° 4 : En quoi les différentes formes cliniques modifient-elles la stratégie thérapeutique dans le rhumatisme psoriasique ? Question n° 5 : Quelle attitude thérapeutique doit-on adopter devant un rhumatisme psoriasique débutant ? 2- La revue de la littérature a permis de sélectionner 73 articles sur le titre et le résumé. 3- À partir des résultats de la revue de la littérature et de l’opinion d’experts, 6 recommandations ont été validées par un vote final par l’ensemble des participants. Conclusion: Six recommandations sur les traitements médicamenteux (hors biothérapies) dans la prise en charge de patients atteints de rhumatisme psoriasique périphérique ont été élaborées. Elles apportent un élément obj ectif et consensuel de réponse à des questions cliniques pour la pratique quotidienne. [Copyright &y& Elsevier]

Objective: To develop clinical practice guidelines for the evaluation and management of cardiovascular risk in patients with rheumatoid arthritis (RA), using the evidence-based approach and expert opinion.Methods: Recommendations were developed using the evidence-based approach and expert opinion: A scientific committee used a Delphi procedure to select five questions, which formed the basis for developing the recommendations; Evidence providing answers to the five questions was sought in the literature; Based on this evidence, recommendations were developed by a panel of experts.Results: The recommendations were as follows: 1) In patients with RA, attention should be given to the risk of cardiovascular disease, which is responsible for an excess burden of morbidity and mortality; 2) It must be recognized that RA may be an independent cardiovascular risk factor. Persistent inflammation is an additional risk factor; 3) The cardiovascular risk should be evaluated, and modifiable risk factors should be corrected; 4) In patients with RA requiring glucocorticoid therapy, the need for cardiovascular risk minimization is among the reasons that mandate the use of the minimal effective dose; 5) It should be recognized that methotrexate may protect against cardiovascular mortality in patients with RA; 6) It should be recognized that TNFalpha antagonists remain contraindicated in patients with RA and severe heart failure. TNFalpha antagonists do not seem to worsen moderate heart failure and may protect against cardiovascular mortality; 7) AFSSAPS recommendations about LDL-cholesterol objectives should be followed, with active RA being counted as a cardiovascular risk factor; 8) In patients with RA, statin therapy should be considered only when cholesterol levels are elevated despite appropriate dietary treatment; 9) RA per se does not indicate aspirin for primary prevention. When aspirin is used for secondary prevention, it should be recognized that concomitant treatment with nonsteroidal antiinflammatory drugs (NSAIDs) may decrease the antiplatelet effects and increase the gastrointestinal side effects of aspirin therapy. [ABSTRACT FROM AUTHOR]

Résumé: Objectif: L’association de traitements de fond conventionnels reste une option thérapeutique rare dans le traitement de la polyarthrite rhumatoïde (PR). Les études publiées sur le sujet sont contradictoires. Nous avons évalué l’intérêt de la triple association méthotrexate, salazopyrine et hydroxychloroquine comme traitement de fond de la PR. Matériels et Méthodes: Toutes les études randomisées évaluant l’intérêt de la triple association méthotrexate, salazopyrine et hydroxychloroquine dans la polyarthrite rhumatoïde ont été systématiquement recherchées dans les bases de données Medline, Cochrane et Embase. Les données concernant l’activité de la maladie, l’évaluation du nombre de jour en arrêt maladie et l’évolution structurale ont été collectées. Résultats: Sur les 495 résumés analysés, 8 articles issus de 5 études ont finalement été inclus. Dans la PR naïve de traitement de fond, la triple association est supérieure à la poursuite d’une monothérapie et a une efficacité comparable à l’association méthotrexate + étanercept. Dans la PR en réponse inadéquate au méthotrexate, l’efficacité de la triple association est supérieure à la poursuite de la monothérapie sur l’activité de la maladie mais l’impact reste similaire sur le nombre de jour en arrêt maladie. Il existe par contre dans ce contexte une infériorité sur l’évolution structurale de la triple association sur l’association méthotrexate + infliximab. Conclusion: La triple association méthotrexate, salazopyrine et hydroxychloroquine est une option thérapeutique efficace dans la prise en charge de la PR pouvant être proposé notamment en cas de contre-indication aux biothérapies. [Copyright &y& Elsevier]

Résumé: Objectif: Présenter les possibilités d’optimisation du méthotrexate (MTX) dans le traitement de la polyarthrite rhumatoïde (PR) en pratique courante, à partir d’une analyse systématique de la littérature. Méthodes: Une recherche systématique de la littérature a été effectuée dans les bases de données PUBMED, EMBASE, COCHRANE et à partir des communications des congrès de l’ACR et de l’EULAR pour identifier les références ayant trait à la posologie d’initiation, aux paliers et à la vitesse d’augmentation, à la posologie maximale et aux différentes voies d’administration du MTX dans la PR. La qualité méthodologique de chaque étude sélectionnée a été évaluée au moyen d’une échelle adaptée. Résultats: La recherche bibliographique a permis d’obtenir 519 références. Après une première sélection sur les titres et les résumés, puis lecture des articles, 11 études ont été retenues. Elles démontrent une efficacité clinique supérieure en initiant le MTX à des fortes posologies (supérieure à 10 mg/semaine par voie orale) puis en augmentant mensuellement la posologie du MTX par paliers de 5 mg/mois, de manière à atteindre rapidement une dose de 25 à 30 mg/semaine, à adapter selon le niveau d’activité clinique et la tolérance de chaque patient * [*] Dans les recommandations HAS sur la polyarthrite rhumatoïde, la posologie maximale proposée est de 25 mg/semaine, à adapter au contexte clinique et à la tolérance au traitement. . à posologie égale, la voie parentérale est plus efficace que la voie orale et mieux tolérée sur le plan digestif. Conclusion: L’ensemble des informations apportées par ces études devraient permettre une meilleure prise en charge des patients traités par MTX dans la PR. [Copyright &y& Elsevier]