Rheumatoid Arthritis: Grange L

Gaudin P, Leguen-Guegan S, Allenet B, Baillet A, Grange L, Juvin R. · Department of Rheumatology, Hôpital Sud, Teaching Hospital, BP 338, 38434 Echirolles cedex, France. · Joint Bone Spine. · Pubmed #17913551 No free full text.

Abstract: INTRODUCTION: Dynamic exercise therapy as defined by the American College of Sports Medicine for healthy individuals is of unclear relevance to patients with rheumatoid arthritis (RA). No recommendations on this issue are available. Few studies have evaluated the optimal program, frequency, or target population; furthermore, there is no consensus about the best assessment tools for monitoring clinical, functional, and structural parameters during dynamic exercise therapy in patients with RA. METHODS: We conducted an extensive review of the literature published between 1964 and 2005. We identified nine randomized controlled studies that provided a high level of proof regarding the effects of dynamic exercise therapy in RA patients older than 18 years of age. RESULTS: Dynamic exercise programs improve aerobic capacity and muscle strength in patients with RA. Their effects on functional capacity are unclear, and many sources of bias influenced the study results. The clinical and laboratory safety profiles were good. The structural impact of dynamic exercise remains to be determined.

Marotte H, Pallot-Prades B, Grange L, Gaudin P, Alexandre C, Miossec P. · Hospices Civils de Lyon-bioMérieux Research Unit on Rheumatoid Arthritis, Hopital Edouard Herriot, place d'Arsonval, 69437 Lyon Cedex 03, France. · Arthritis Res Ther. · Pubmed #17597527 links to  free full text

Abstract: The goal of the present study was to record changes in bone mineral density (BMD) and markers of bone turnover in patients with rheumatoid arthritis (RA) who were treated with methotrexate combined (or not combined) with infliximab. Included were 90 patients with RA who required anti-TNF-alpha therapy with infliximab because of persistent active disease despite treatment with methotrexate. The historical control group included 99 patients with RA who were treated with methotrexate at a time when anti-TNF-alpha treatment was not yet available. Lumbar and femoral neck BMD was measured using dual energy X-ray absorptiometry at baseline and 1 year later. Osteocalcin, C-terminal cross-linked telopeptide of type I collagen, parathyroid hormone and 25-hydroxycholecalciferol were measured in plasma at baseline and 1 year later. At 1 year BMD had decreased in the control group at spine (P < 0.01) and femoral neck (P < 0.001). In contrast, BMD at spine and femoral neck did not change after 1 year of infliximab treatment. At the same time point, no change in bone remodelling markers was observed. No association was observed between clinical response and changes in BMD, indicating that even those who did not respond clinically did not lose bone over a 1-year period. These data confirm the BMD decrease observed in RA patients treated with methotrexate alone. This bone loss was prevented by infliximab therapy. Importantly, this beneficial effect was also observed in apparent nonresponders.

Baillet A, Payraud E, Niderprim VA, Nissen MJ, Allenet B, François P, Grange L, Casez P, Juvin R, Gaudin P. · 1Clinic of Rheumatology, Hôpital Sud, Echirolles, Hôpital A Michallon, Grenoble, France. · Rheumatology (Oxford). · Pubmed #19211654 No free full text.

Abstract: OBJECTIVE: To evaluate the functional, clinical, radiological and quality of life outcomes of a 4-week dynamic exercise programme (DEP) in RA. METHODS: Patients matched on the principal medico-social parameters were randomly assigned to either the DEP or the conventional joint rehabilitation group. Primary end point for judging effectiveness was functional status assessed by HAQ. Secondary outcomes included Nottingham Health Profile (NHP), Arthritis Impact Measurement Scale 2-Short Form (AIMS2-SF) and radiological worsening measured by Simple Narrowing Erosion Score (SENS). Clinical evaluation consisted of disease activity score (DAS 28), cycling aerobic fitness and dexterity. Dexterity was measured using Sequential Occupational Dexterity Assessment (SODA) and Duruoz Hand Index (DHI). Data were collected at baseline 1, 6 and 12 months. RESULTS: Fifty patients were enrolled. HAQ improved throughout the length of the trial in the DEP group. This improvement was greater in DEP than in the standard joint rehabilitation group at 1 month (-0.2 vs no variation from baseline, P = 0.04), but not at 6 months (-0.2 vs -0.1 in control group, P = 0.25) or 12 months (-0.1 vs no variation in control group, P = 0.51). DEP improved NHP (-23 vs + 7% in control group, P = 0.01) and aerobic fitness (+0.3 vs + 0.1 km per 5 min in control group, P = 0.02) at 1 month but the progress was not statistically significant thereafter. DEP also improved DHI, SODA, DAS 28 and AIMS2-SF, although not significantly. CONCLUSION: DEP was effective on functional status assessed by HAQ, quality of life and aerobic fitness at 1 month.

Trocmé C, Marotte H, Baillet A, Pallot-Prades B, Garin J, Grange L, Miossec P, Tebib J, Berger F, Nissen MJ, Juvin R, Morel F, Gaudin P. · GREPI CNRS UMR 5525, INSERM IFR 130, Université J Fourier, Grenoble, France. · Ann Rheum Dis. · Pubmed #18664547 No free full text.

Abstract: OBJECTIVES: The use of biologicals such as infliximab has dramatically improved the treatment of rheumatoid arthritis (RA). However, factors predictive of therapeutic response need to be identified. A proteomic study was performed prior to infliximab therapy to identify a panel of candidate protein biomarkers of RA predictive of treatment response. METHODS: Plasma profiles of 60 patients with RA (28 non-responders (as defined by the American College of Rheumatology 20% improvement criteria (ACR20)) negative and 32 responders (ACR70 positive) to infliximab) were studied by surface enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI-TOF MS) technology on two types of arrays, an anion exchange array (SAX2) and a nickel affinity array (IMAC3-Ni). Biomarker characterisation was carried out using classical biochemical methods (purification by ammonium sulfate precipitation or metal affinity chromatography) and identification by matrix assisted laser desorption/ionisation time-of-flight (MALDI-TOF) MS analysis. RESULTS: Two distinct protein profiles were observed on both arrays and several proteins were differentially expressed in both patient populations. Five proteins at 3.86, 7.77, 7.97, 8.14 and 74.07 kDa were overexpressed in the non-responder group, whereas one at 28 kDa was increased in the responder population (sensitivity>56%, specificity>77.5%). Moreover, combination of several biomarkers improved the sensitivity and specificity of the detection of patient response to over 97%. The 28 kDa protein was characterised as apolipoprotein A-I and the 7.77 kDa biomarker was identified as platelet factor 4. CONCLUSIONS: Six plasma biomarkers are characterised, enabling the detection of patient response to infliximab with high sensitivity and specificity. Apolipoprotein A-1 was predictive of a good response to infliximab, whereas platelet factor 4 was associated with non-responders.

Boignard A, Salvat-Melis M, Carpentier PH, Minson CT, Grange L, Duc C, Sarrot-Reynauld F, Cracowski JL. · Laboratory HP2, EA 3745 Inserm ESPRI, Grenoble Medical School, France. · Arthritis Res Ther. · Pubmed #16207327 links to  free full text

Abstract: Accurate and sensitive measurement techniques are a key issue in the quantification of the microvascular and endothelial dysfunction in systemic sclerosis (SSc). Thermal hyperemia comprises two separate mechanisms: an initial peak that is axon reflex mediated; and a sustained plateau phase that is nitric oxide dependent. The main objective of our study was to test whether thermal hyperemia in patients with SSc differed from that in patients with primary Raynaud's phenomenon (RP) and healthy controls. In a first study, we enrolled 20 patients suffering from SSc, 20 patients with primary RP and 20 healthy volunteers. All subjects were in a fasting state. Post-occlusive hyperemia, 0.4 mg sublingual nitroglycerin challenge and thermal hyperemia were performed using laser Doppler flowmetry on the distal pad of the third left finger. In a second study, thermal hyperemia was performed in 10 patients with rheumatoid arthritis and 10 patients with primary RP. The thermal hyperemia was dramatically altered in terms of amplitude and kinetics in patients with SSc. Whereas 19 healthy volunteers and 18 patients with primary RP exhibited the classic response, including an initial peak within the first 10 minutes followed by a nadir and a second peak, this occurred only in four of the SSc patients (p < 0.0001). The 10 minutes thermal peak was 43.4 (23.2 to 63), 42.6 (31 to 80.7) and 27 (14.7 to 51.4) mV/mm Hg in the healthy volunteers, primary RP and SSc groups, respectively (p = 0.01), while the 44 degrees C thermal peak was 43.1 (21.3 to 62.1), 42.6 (31.6 to 74.3) and 25.4 (15 to 52.4) mV/mm Hg, respectively (p = 0.01). Thermal hyperemia was more sensitive and specific than post-occlusive hyperhemia for differentiating SSc from primary RP. In patients with rheumatoid arthritis, thermal hyperemia was also altered in terms of amplitude. Thermal hyperemia is dramatically altered in patients with secondary RP in comparison with subjects with primary RP. Further studies are required to determine the mechanisms of this altered response, and whether it may provide additional information in a clinical setting.

Marotte H, Pallot-Prades B, Grange L, Tebib J, Gaudin P, Alexandre C, Blond JL, Cazalis MA, Mougin B, Miossec P. · Clinical Immunology Unit, Departments of Immunology and Rheumatology, Hôpital Edouard Hérriot, 69437 Lyon Cedex 03, France. · Ann Rheum Dis. · Pubmed #16096333 links to  free full text

Abstract: OBJECTIVE: To determine whether joint destruction, indication for, and response to infliximab in rheumatoid arthritis are associated with the shared epitope (SE) or selected cytokine gene polymorphisms (interleukin (IL) 1B, IL1-RN, and tumour necrosis alpha). METHODS: In a large rheumatoid arthritis population of 930 patients from the same area (Rhône-Alpes, France), patients with (n = 198) or without infliximab treatment (n = 732) were compared according to their genetic status. Clinical, biological, and radiological data were collected. Typing for SE status and cytokine polymorphisms was carried out using enzyme linked oligosorbent assay. Statistical analysis was by chi(2) testing and calculation of odds ratios (OR). RESULTS: A dose relation was observed between the number of SE copies and joint damage in the whole rheumatoid population (OR, 1 v 0 SE copy = 2.38 (95% confidence interval, 1.77 to 3.19), p<0.001; OR 2 v 0 SE copy = 3.92 (2.65 to 5.80), p<0.001. The SE effect increased with disease duration but was not significant before two years. Selection for infliximab treatment (n = 198) was associated with increased disease activity, joint damage, and the presence of the SE with a dose effect. In all, 66.2% patients achieved an ACR20 improvement. No clinical or genetic factors were able to predict the clinical response to infliximab. CONCLUSIONS: This post-marketing study in a large cohort of rheumatoid arthritis patients indicates a linkage between rheumatoid arthritis severity, selection for treatment with infliximab, and the presence and dose of the SE.