Rheumatoid Arthritis: Pavy S

Miceli-Richard C, Gestermann N, Amiel C, Sellam J, Ittah M, Pavy S, Urrutia A, Girauld I, Carcelain G, Venet A, Mariette X. · Rhumatologie, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, 94275 Le Kremlin Bicêtre, France. · Arthritis Res Ther. · Pubmed #19470150 links to  free full text

Abstract: INTRODUCTION: There is a suspicion of increased risk of Epstein-Barr virus (EBV)-associated lymphoproliferations in patients with inflammatory arthritides receiving immunosuppressive drugs. We investigated the EBV load and EBV-specific T-cell response in patients treated with methotrexate (MTX) or anti-TNF therapy. METHODS : Data for patients with rheumatoid arthritis (RA) (n = 58) or spondylarthropathy (SpA) (n = 28) were analyzed at baseline in comparison with controls (n = 22) and after 3 months of MTX or anti-TNF therapy for EBV load and EBV-specific IFNgamma-producing T cells in response to EBV latent-cycle and lytic-cycle peptides. RESULTS: The EBV load and the number of IFNgamma-producing T-cells after peptide stimulation were not significantly different between groups at baseline (P = 0.61 and P = 0.89, respectively). The EBV load was not significantly modified by treatment, for RA with MTX (P = 0.74) or anti-TNF therapy (P = 0.94) or for SpA with anti-TNF therapy (P = 1.00). The number of EBV-specific T cells was not significantly modified by treatment, for RA with MTX (P = 0.58) or anti-TNF drugs (P = 0.19) or for SpA with anti-TNF therapy (P = 0.39). For all patients, the EBV load and EBV-specific T cells were significantly correlated (P = 0.017; R = 0.21). For most patients, short-term exposure (3 months) to MTX or anti-TNF did not alter the EBV load or EBV-specific T-cell response but two patients had discordant evolution. CONCLUSIONS: These data are reassuring and suggest there is no short-term defect in EBV-immune surveillance in patients receiving MTX or anti-TNF drugs. However, in these patients, long term follow-up of EBV-specific T-cell response is necessary and the role of non-EBV-related mechanisms of lymphomagenesis is not excluded.

Pham T, Gossec L, Constantin A, Pavy S, Bruckert E, Cantagrel A, Combe B, Flipo RM, Goupille P, Le Loët X, Mariette X, Puéchal X, Schaeverbeke T, Sibilia J, Tebib J, Wendling D, Dougados M. · Service de rhumatologie, CHU de la Conception, Marseille, France. · Joint Bone Spine. · Pubmed #16690341 No free full text.

Abstract: 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.

Perdriger A, Mariette X, Kuntz JL, Brocq O, Kara-Terki R, Loet XL, Cantagrel A, Pavy S, Deslandre CJ, Debiais F, Combe B, Anonymous00196. · Department of Rheumatology, Medical University, Rennes, France. · J Rheumatol. · Pubmed #16652418 No free full text.

Abstract: OBJECTIVE: To investigate the safety of infliximab (INF) combination therapy with leflunomide (LEF) or azathioprine (AZA) in patients with rheumatoid arthritis (RA). METHOD: A standardized questionnaire on the use of INF in combination with LEF or AZA was mailed to hospital physicians and collected over a 2 month period. Adverse events (AE) and the reasons for withdrawal of combination therapy were analyzed. RESULTS: Data on 225 patients with RA were collected retrospectively. INF was used in combination with LEF in 171 patients and with AZA in 54. The duration of INF exposure was similar in both groups (mean 8.8 mo). AE were reported in 75 patients (33.3%), 60 LEF/INF (35%) and 15 AZA/INF combinations (27.8%) (p=nonsignificant). No unexpected AE were observed. The main AE were infections (6.2%), cytopenia (5.8%), hepatotoxicity (5.8%), reactions to infusion (5.3%), and skin reactions (4%). At the time the questionnaires were sent out, 161 patients were continuing combination therapies. The main reasons for drug withdrawal were AE (53 patients, 23.5%), inefficacy (10 patients, 4%), and one temporary discontinuation for surgery. CONCLUSION: Our study suggests that INF used in combination with LEF or AZA could be an alternative to methotrexate/INF combinations.

Gossec L, Pavy S, Pham T, Constantin A, Poiraudeau S, Combe B, Flipo RM, Goupille P, Le Loët X, Mariette X, Puéchal X, Wendling D, Schaeverbeke T, Sibilia J, Tebib J, Cantagrel A, Dougados M. · Service de rhumatologie B, CHU de Cochin, 27, rue du Faubourg Saint-Jacques, 75014 Paris, France. · Joint Bone Spine. · Pubmed #16626995 No free full text.

Abstract: OBJECTIVE: To develop clinical practice guidelines for the use of nonpharmacological treatments in patients with early rheumatoid arthritis (RA), using the evidence-based approach and expert opinion. METHODS: A scientific committee used a Delphi prioritization procedure to select five questions. Evidence providing answers to the five questions was sought in the literature and presented to a panel of rheumatologists. The panel developed five detailed recommendations, filling gaps in evidence with their expert opinion. The strength of each recommendation was determined. RESULTS: Of the 565 publications retrieved by the literature review, 198 were included in the analysis. The five recommendations on nonpharmacological treatments for early RA were validated by a final vote among all participants. The recommendations are as follows: (1) physicians may decide to provide joint protection education to patients with potentially severe early RA, with the knowledge that structured joint protection programs have not been found effective; (2) physical exercise and sports can be recommended to patients with early RA; muscle strength exercises are advisable; (3) in patients with early RA, metatarsal pain and/or foot alignment abnormalities should be looked for regularly, and appropriate insoles should be prescribed if needed; (4) dietary measures and nutritional supplements are not indicated as part of the treatment of early RA; (5) elimination diets, particularly those with low intakes of dairy products, should be discouraged in patients with early RA. CONCLUSION: These recommendations should help to improve practice uniformity and, ultimately, to improve the management of RA.

Pavy S, Constantin A, Pham T, Gossec L, Maillefert JF, Cantagrel A, Combe B, Flipo RM, Goupille P, Le Loët X, Mariette X, Puéchal X, Schaeverbeke T, Sibilia J, Tebib J, Wendling D, Dougados M. · Service de rhumatologie A, CHU Cochin, 27, rue du Faubourg-Saint-Jacques, 75014 Paris, France. · Joint Bone Spine. · Pubmed #16626993 No free full text.

Abstract: 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.