Rheumatoid Arthritis: Klemmer N

Vittecoq O, Lequerré T, Goëb V, Le Loët X, Abdesselam TA, Klemmer N. · Department of Rheumatology, Rouen University Hospital & Inserm U905, Rouen, France. · Best Pract Res Clin Rheumatol. · Pubmed #19028372 No free full text.

Abstract: Smoking has an impact on the development and outcome of rheumatoid arthritis (RA) and lupus. In RA, smoking is associated with the development of the anti-cyclic citrullinated peptide (CCP2)-positive subset. This risk is increased in heavy smokers carrying at least one copy of the HLA DRB1 shared epitope (SE) alleles. Whereas this interaction between smoking and SE relevant in northern Europe, discrepant results have been observed in other geographic locations, suggesting the involvement of other environmental stimuli and/or gene polymorphisms. There is no interaction between tobacco exposure and PTPN22 1858T for the development of anti-CCP-positive or anti-CCP-negative RA. A strong association exists between smoking and the occurrence of extra-articular manifestations (subcutaneous nodules and cardiovascular events), but smoking has no influence on radiographic outcome. In lupus, tobacco exposure has an impact on the production of anti-double-stranded Desoxyribonuclic (dsDNA) and possibly on the development of the disease, as well as on disease activity/severity. In both diseases, smoking might interfere with drug efficacy.

Le Loët X, Klemmer N. · Service de rhumatologie et Inserm U 519, IFR 23, CHU de Rouen. · Rev Prat. · Pubmed #16544921 No free full text.

Abstract: The diagnosis of early arthritis is often difficult even though it is an important issue. A step-by-step clinical examination is necessary to make the diagnosis of "joint emergency": an infection must be suspected when fever is associated with arthritis. Then, classification of early arthritis will be carried on with a special attention to rheumatoid arthritis when the rheumatism is persistent and erosive. However, arthritis might be undifferentiated for several months to years; such an explanation should be given to the patient. A tight follow-up is necessary.

Lequerré T, Jouen F, Brazier M, Clayssens S, Klemmer N, Ménard JF, Mejjad O, Daragon A, Tron F, Le Loët X, Vittecoq O. · Department of Rheumatology, Rouen University Hospital, Rouen Cedex, France. · Rheumatology (Oxford). · Pubmed #16899502 links to  free full text

Abstract: OBJECTIVES: To identify biochemical, immunological and bone markers as predictors of rheumatoid arthritis (RA) patients' responses to infliximab. METHODS: A total of 76 patients with active RA (American College of Rheumatology criteria), refractory to disease-modifying anti-rheumatic drugs, including methotrexate, received infliximab (3 mg/kg) infusions at weeks 0, 2, 6, and then every 8 weeks in combination with methotrexate or leflunomide. At week 14, infliximab efficacy was evaluated using disease activity score (DAS)28. A serum sample, collected just before starting infliximab, was tested by ELISA (unless stated otherwise) for the following immunological markers: rheumatoid factor by agglutination and ELISA (IgA, IgG and IgM isotypes); anti-cyclic citrullinated protein; autoantibodies recognizing calpastatin domain I and its 27 C-terminal fragment, glucose-6-phosphate isomerase, alpha-enolase; anti-keratin and anti-perinuclear factor antibodies (immunofluorescence); biochemical markers: C-reactive protein (nephelometry), metalloproteinase-1 and -3, tissue inhibitors of metalloproteinases-1 and -2, antioxidants (vitamins A and E; selenium); bone resorption markers: pyridinoline, deoxypyridinoline, osteoprotegerin, soluble receptor activator of nuclear factor-kappaB ligand, cartilage oligomeric matrix protein. Each parameter's predictive value of the response to infliximab was analysed using Fisher's exact, Mann-Whitney and chi-square tests. Hierarchical clustering was performed with The Institute for Genomic Research (TIGR) multiple experiment viewer software. RESULTS: Good, moderate and non-responder rates were 6.5, 61.8 and 31.5%, respectively. No significant difference was observed between responders and non-responders, regardless of the serum parameters considered. Analysis of dichotomous or continuous variables failed to identify markers predictive of a good or poor response to infliximab. CONCLUSION: The search for soluble markers in RA patients' sera likely to predict response to infliximab because of their involvement in RA pathogenesis seems disappointing. However, because of the limited power to detect smaller differences in biomarkers, the present study is a preliminary exploratory analysis.

Lequerré T, Vittecoq O, Klemmer N, Goëb V, Pouplin S, Menard JF, Daragon A, Mejjad O, Le Loët X. · Department of Rheumatology, Rouen University Hospital, Rouen, France. · J Rheumatol. · Pubmed #16758513 No free full text.

Abstract: OBJECTIVE: To suggest recommendations for management of acute infusion reactions induced by infliximab in patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA). METHODS: In total, 203 patients were treated with infliximab (120 ml/h). Prevalence of acute infusion reaction was evaluated. To manage these conditions, recommendations were devised according to the type and the severity of clinical manifestations, which were classified beforehand in 2 groups: A (hypertension, pruritus, sudden flush, vomiting, tachycardia or bradycardia, shivers, fever) and B (urticaria, tickling throat, Quincke's edema, dyspnea, and hypotension). Recommendations were based mainly on adjustment of the infusion rate. RESULTS: It was observed that 23/203 patients (11.3%) had acute infusion reactions. Among them and prior to our recommendations, infliximab was completely discontinued in 8/23 patients. After our recommendations were implemented, 15/23 patients presented an acute infusion reaction: 8 and 7 patients with symptoms of Group A and B, respectively. In Group A (8 patients), reducing the infusion rate to 60-80 ml/h led to disappearance of symptoms; the modified treatment was then maintained. In Group B (7 patients), the infusion was immediately stopped and appropriate drugs were administered. Once clinical manifestations were alleviated, the infusion was resumed (60 ml/h). Prior to subsequent infusions (60 ml/h), a premedication was administered. CONCLUSION: Based on these recommendations, infliximab could be maintained with great efficacy on disease activity in every patient with an acute infusion reaction. Our recommendations permit sustained administration of infliximab and allow every patient to benefit from this therapy.