Rheumatoid Arthritis: Gaudin P

Gaudin P. · No affiliation provided · Rev Med Interne. · Pubmed #18571291 No free full text.

This publication has no abstract.

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.

Tebib J, Mariette X, Bourgeois P, Flipo RM, Gaudin P, Le Loët X, Gineste P, Guy L, Mansfield CD, Moussy A, Dubreuil P, Hermine O, Sibilia J. · Service de Rhumatologie, Centre Hospitalier Lyon-Sud, 765 chemin du Grand-Revoyet, 69495 Pierre-Bénite, France. · Arthritis Res Ther. · Pubmed #19549290 links to  free full text

Abstract: INTRODUCTION: Since current treatment options for patients suffering from active rheumatoid arthritis (RA) remain inadequate, especially for those unresponsive to disease-modifying antirheumatic drugs (DMARDs), new and improved medication is needed. This study evaluates the safety and efficacy of masitinib (AB1010), a potent and selective protein tyrosine kinase inhibitor of c-KIT, in the monotherapy treatment of DMARD-refractory RA. METHODS: This was a multicentre, uncontrolled, open-label, randomised, dose-ranging, phase 2a trial. Masitinib was administered orally to 43 patients who had inadequate response to DMARDs, at initial randomised dosing levels of 3 and 6 mg/kg per day over a 12-week period. Dose adjustment was permitted based upon tolerability and response criteria. Efficacy was assessed via American College of Rheumatology 20%/50%/70% improvement criteria (ACR20/50/70) responses, disease activity score using 28 joint counts (DAS28), index of improvement in RA (ACRn) and C-reactive protein (CRP) improvement, relative to baseline at week 12. RESULTS: Improvement was observed in all efficacy endpoints, including ACR20/50/70 scores of 54%, 26% and 8%, respectively, and a reduction in CRP level by greater than 50% for approximately half the population. This improvement was sustainable throughout an extension phase (> 84 weeks) and was also independent of initial DMARD resistance (anti-tumour necrosis factor-alpha and/or methotrexate). A relatively high patient withdrawal rate (37%) required the use of last observation carried forward (LOCF) data imputation. Incidence of adverse events was high (95%), although the majority were of mild or moderate severity with a considerable decline in frequency observed after 12 weeks of treatment. Two nonfatal serious adverse events were reported. Dose-response analyses tentatively indicate that an initial dosing level of 6.0 mg/kg per day administered orally in two daily intakes is the most appropriate, based upon potency and tolerability trends. CONCLUSIONS : Treatment with masitinib improved DMARD-refractory active RA. Following an initial high incidence of mostly mild to moderate side effects during the first 12 weeks of treatment, masitinib appears to be generally well tolerated. This, together with evidence of a sustainable efficacy response, suggests that masitinib is suitable for long-term treatment regimens. Since this was the first study of masitinib in a nononcologic pathology, the relatively high patient withdrawal rate observed can be partly attributed to a highly cautious response to adverse events. There is sufficient compelling evidence to warrant further placebo-controlled investigation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00831922.

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.

Marotte H, Farge P, Gaudin P, Alexandre C, Mougin B, Miossec P. · Hospices Civils de Lyon-bioMérieux Research Unit on Rheumatoid Arthritis, and Faculty of Odontology, University Lyon I, France. · Ann Rheum Dis. · Pubmed #16284099 links to  free full text

Abstract: OBJECTIVE: To evaluate a possible association between wrist and periodontal destruction in rheumatoid arthritis, and between periodontal destruction, dry mouth, and labial salivary gland biopsy and the contribution of genetic factors (the shared epitope (SE) and IL1B (+3954) or TNFA (-238 or -308) gene polymorphisms). METHODS: 147 patients with rheumatoid arthritis were enrolled. Periodontal damage was defined according to the Hugoson and Jordan criteria on panoramic dental x rays. Typing for the SE and cytokine polymorphisms was undertaken by enzyme linked oligosorbent assay. Odds ratios (OR), relative risk (RR), and chi2 values were calculated to quantify associations. RESULTS: An association was observed between wrist and periodontal bone destruction (chi2=11.82; p<0.001): 63 patients had both wrist and periodontal destruction, 31 had wrist destruction alone, 20 had periodontal destruction alone, and 33 had no destruction at either site. An association was seen between a positive labial salivary gland biopsy and periodontal bone destruction (RR=2.73 (95% CI, 1.35 to 5.51), p<0.01, n=41) or wrist bone destruction (RR=4.52 (1.96 to 10.45), p<0.001, n=41). The SE was associated with wrist bone destruction (OR=2.5 (1.16 to 5.42), p<0.05) and periodontal bone destruction (OR=2.2 (1.04 to 4.84), p<0.05). No association was found between the selected cytokine polymorphisms and bone destruction. CONCLUSIONS: A strong association was found between wrist and periodontal bone destruction. The destruction risk was further increased in patients with sicca syndrome. The SE appears to be a severity genetic marker for both wrist and periodontal bone destruction.

Ornetti P, Solau E, Gaudin P, Sibilia J, Berthelot JM, Puechal X, Tavernier C, Maillefert JF, Anonymous00229. · No affiliation provided · Ann Rheum Dis. · Pubmed #16100349 links to  free full text

This publication has no abstract.

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.

Gaudin P, Ijaz S, Tuke PW, Marcel F, Paraz A, Seigneurin JM, Mandrand B, Perron H, Garson JA. · Department of Virology, Royal Free and University College Medical School, London, UK. · Rheumatology (Oxford). · Pubmed #10986298 links to  free full text

Abstract: OBJECTIVES: To determine whether the recently identified multiple sclerosis-associated retrovirus, MSRV, is detectable in the serum and synovial fluid of patients with rheumatoid arthritis (RA). METHODS: A reverse transcription-polymerase chain reaction (RT-PCR) assay was used to seek evidence of particle-associated MSRV/HERV-W RNA in the plasma and synovial fluid of patients with RA and controls. Stringent precautions were taken to avoid detection of contaminating human genomic DNA and cellular RNA sequences. RESULTS: Thirty-seven plasma samples were tested (20 from RA patients and 17 from controls) but none had detectable MSRV/HERV-W RNA. Synovial fluid samples were available from nine patients with RA and 10 controls. Particle-associated MSRV/HERV-W RNA was reproducibly detected in two of nine synovial fluid samples from RA patients and in one control sample. The identity of RT-PCR products was confirmed by sequencing. CONCLUSION: MSRV/HERV-W RNA sequences are detectable in the synovial fluid of a small proportion of RA patients, but this phenomenon may not be specific to RA.

Maillefert JF, Sibilia J, Toussirot E, Vignon E, Eschard JP, Lorcerie B, Juvin R, Parchin-Geneste N, Piroth C, Wendling D, Kuntz JL, Tavernier C, Gaudin P. · Department of Rheumatology, Dijon University Hospital, France. · Rheumatology (Oxford). · Pubmed #10534549 links to  free full text

Abstract: OBJECTIVE: To obtain an overview of rheumatic disorders occurring after hepatitis B vaccination. METHODS: A questionnaire was sent to rheumatology departments in nine French hospitals. Criteria for entry were rheumatic complaints of 1 week's duration or more, occurrence during the 2 months following hepatitis B vaccination, no previously diagnosed rheumatic disease and no other explanation for the complaints. RESULTS: Twenty-two patients were included. The observed disorders were as follows: rheumatoid arthritis for six patients; exacerbation of a previously non-diagnosed systemic lupus erythematosus for two; post-vaccinal arthritis for five; polyarthralgia-myalgia for four; suspected or biopsy-proved vasculitis for three; miscellaneous for two. CONCLUSIONS: Hepatitis B vaccine might be followed by various rheumatic conditions and might trigger the onset of underlying inflammatory or autoimmune rheumatic diseases. However, a causal relationship between hepatitis B vaccination and the observed rheumatic manifestations cannot be easily established. Further epidemiological studies are needed to establish whether hepatitis B vaccination is associated or not with an incidence of rheumatic disorders higher than normal.

Gaudin P, Moutet F, Tuke PW, Garson JA. · No affiliation provided · Arthritis Rheum. · Pubmed #10555048 links to  free full text

This publication has no abstract.