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2.
Ann Rheum Dis ; 75(6): 1108-13, 2016 Jun.
Article En | MEDLINE | ID: mdl-26048170

OBJECTIVES: Little data are available regarding the rate and predicting factors of serious infections in patients with rheumatoid arthritis (RA) treated with abatacept (ABA) in daily practice. We therefore addressed this issue using real-life data from the Orencia and Rheumatoid Arthritis (ORA) registry. METHODS: ORA is an independent 5-year prospective registry promoted by the French Society of Rheumatology that includes patients with RA treated with ABA. At baseline, 3 months, 6 months and every 6 months or at disease relapse, during 5 years, standardised information is prospectively collected by trained clinical nurses. A serious infection was defined as an infection occurring during treatment with ABA or during the 3 months following withdrawal of ABA without any initiation of a new biologic and requiring hospitalisation and/or intravenous antibiotics and/or resulting in death. RESULTS: Baseline characteristics and comorbidities: among the 976 patients included with a follow-up of at least 3 months (total follow-up of 1903 patient-years), 78 serious infections occurred in 69 patients (4.1/100 patient-years). Predicting factors of serious infections: on univariate analysis, an older age, history of previous serious or recurrent infections, diabetes and a lower number of previous anti-tumour necrosis factor were associated with a higher risk of serious infections. On multivariate analysis, only age (HR per 10-year increase 1.44, 95% CI 1.17 to 1.76, p=0.001) and history of previous serious or recurrent infections (HR 1.94, 95% CI 1.18 to 3.20, p=0.009) were significantly associated with a higher risk of serious infections. CONCLUSIONS: In common practice, patients treated with ABA had more comorbidities than in clinical trials and serious infections were slightly more frequently observed. In the ORA registry, predictive risk factors of serious infections include age and history of serious infections.


Abatacept/adverse effects , Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/drug therapy , Immunosuppressive Agents/adverse effects , Opportunistic Infections/chemically induced , Abatacept/therapeutic use , Adult , Age Factors , Aged , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/epidemiology , Arthritis, Rheumatoid/immunology , Comorbidity , Female , France/epidemiology , Humans , Immunocompromised Host , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Opportunistic Infections/epidemiology , Opportunistic Infections/immunology , Registries , Risk Factors
3.
Ann Rheum Dis ; 74(9): 1684-90, 2015 Sep.
Article En | MEDLINE | ID: mdl-24796335

OBJECTIVES: In France, the prevalence of gout is currently unknown. We aimed to design a questionnaire to detect gout that would be suitable for use in a telephone survey by non-physicians and assessed its performance. METHODS: We designed a 62-item questionnaire covering comorbidities, clinical features and treatment of gout. In a case-control study, we enrolled patients with a history of arthritis who had undergone arthrocentesis for synovial fluid analysis and crystal detection. Cases were patients with crystal-proven gout and controls were patients who had arthritis and effusion with no monosodium urate crystals in synovial fluid. The questionnaire was administered by phone to cases and controls by non-physicians who were unaware of the patient diagnosis. Logistic regression analysis and classification and regression trees were used to select items discriminating cases and controls. RESULTS: We interviewed 246 patients (102 cases and 142 controls). Two logistic regression models (sensitivity 88.0% and 87.5%; specificity 93.0% and 89.8%, respectively) and one classification and regression tree model (sensitivity 81.4%, specificity 93.7%) revealed 11 informative items that allowed for classifying 90.0%, 88.8% and 88.5% of patients, respectively. CONCLUSIONS: We developed a questionnaire to detect gout containing 11 items that is fast and suitable for use in a telephone survey by non-physicians. The questionnaire demonstrated good properties for discriminating patients with and without gout. It will be administered in a large sample of the general population to estimate the prevalence of gout in France.


Arthritis, Rheumatoid/diagnosis , Gout/diagnosis , Osteoarthritis/diagnosis , Spondylarthropathies/diagnosis , Adult , Aged , Arthritis/diagnosis , Arthritis/epidemiology , Arthritis, Rheumatoid/epidemiology , Case-Control Studies , Epidemiologic Studies , France/epidemiology , Gout/epidemiology , Humans , Logistic Models , Middle Aged , Osteoarthritis/epidemiology , Sensitivity and Specificity , Spondylarthropathies/epidemiology , Surveys and Questionnaires , Telephone
4.
Arthritis Care Res (Hoboken) ; 65(11): 1874-9, 2013 Nov.
Article En | MEDLINE | ID: mdl-23754822

OBJECTIVE: We used data from the AutoImmunity and Rituximab (AIR) registry to investigate the safety of surgery for patients with rheumatoid arthritis receiving rituximab (RTX) in routine care. METHODS: Data for patients included in the AIR registry and undergoing surgery during the year following an infusion of RTX were reviewed to describe the frequency of postsurgical complications, compare patients with and without complications, and identify factors associated with complications. RESULTS: We examined data for 133 patients with a known date of surgery and at least 1 followup visit, corresponding to 140 procedures, including 94 orthopedic surgeries (67%) and 23 abdominal surgeries (16.5%). The median delay between surgery and the last RTX infusion was 6.4 months (interquartile range 4.3­ 8.7 months), without any difference between patients with and without complications. Nine patients (6.7%) experienced 12 complications (8.5%), including 8 surgical site infections (5.7%) and 1 death due to septic shock. Postoperative complications occurred after 4.3% of abdominal surgeries (1 of 23) and 7.4% of orthopedic surgeries (7 of 95). On univariate analysis, spine surgery was associated with postoperative complications (P = 0.048). CONCLUSION: In common practice, the risk of complications may be more important in case of spine surgery, but does not seem to be linked to the time between the last RTX infusion and surgery.


Antibodies, Monoclonal, Murine-Derived/administration & dosage , Autoimmunity , Postoperative Complications/epidemiology , Registries , Risk Assessment/methods , Surgical Procedures, Operative , Aged , Aged, 80 and over , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/surgery , Female , Follow-Up Studies , France/epidemiology , Humans , Immunologic Factors/administration & dosage , Incidence , Infusions, Intravenous , Male , Middle Aged , Postoperative Complications/prevention & control , Prognosis , Prospective Studies , Risk Factors , Rituximab , Treatment Outcome
5.
Z Rheumatol ; 71(10): 890-9, 2012 Dec.
Article En | MEDLINE | ID: mdl-22956167

The objective of this study was to investigate patients' perceptions of the acceptability of two devices delivering etanercept for rheumatoid arthritis (RA) treatment and to explore whether specific patients' attributes are associated with device preferences. Two similar multicenter, open-label, randomised, parallel-design studies were conducted in a total of 13 European countries. A total of 640 adult patients with RA were randomised to receive etanercept 50 mg once-weekly subcutaneously for 12 weeks in either a pre-filled syringe (PFS) or a pre-filled pen (PFP). Patient satisfaction at week 12 was measured on a 0- to 10-point Likert scale (primary endpoint). The study was powered to demonstrate non-inferiority of a PFP over PFS for the primary endpoint. At week 12, mean patient satisfaction was 8.3 (± 2.4) points in the pen group and 7.2 (± 2.6) points in the syringe group. Non-inferiority and even superiority of the pen over the syringe was demonstrated. In conclusion, this study showed higher patient satisfaction in the group of patients injecting etanercept with a PFP compared with the group of patients using a PFS.


Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/epidemiology , Immunoglobulin G/administration & dosage , Patient Satisfaction/statistics & numerical data , Receptors, Tumor Necrosis Factor/administration & dosage , Self Administration/instrumentation , Self Administration/statistics & numerical data , Syringes/statistics & numerical data , Antirheumatic Agents/administration & dosage , Arthritis, Rheumatoid/diagnosis , Etanercept , Europe/epidemiology , Female , Humans , Male , Prevalence , Syringes/classification , Treatment Outcome
6.
Ann Rheum Dis ; 71(11): 1815-9, 2012 Nov.
Article En | MEDLINE | ID: mdl-22615458

OBJECTIVES: Very limited data are available regarding the efficacy of abatacept (ABA) in real life. The aims of this study were to determine the efficacy of ABA in rheumatoid arthritis and predicting factors of efficacy in common practice. METHODS: The Orencia and Rheumatoid Arthritis" (ORA) prospective registry, promoted by the French Society of Rheumatology, has included 1003 patients with RA. RESULTS: 773 patients had already fulfilled the 6-month follow-up visit. Only 21.3% of patients would have fulfilled inclusion criteria used in pivotal controlled trials. The European League Against Rheumatism (EULAR) response, was observed in 330 (59.1%) of the 558 assessed patients (good response: 20.4%, moderate response: 38.7%) and was similar in patients who did and in patients who did not fulfill inclusion criteria of controlled trials. Among EULAR responders, initial 28-joint disease activity score (5.4 (4.7-6.5) in responders vs 4.9 (4.0-6.0) in non responders, p< 0.0001), the proportion of rheumatoid factor (75.6% vs 66.7%, p= 0.03) and the proportion of anti-cyclic citrullinated peptide antibody (anti-CCP)-positivity (75.9% vs 62.2%, p= 0.001) were significantly higher. In multivariate analysis adjusted on initial 28-joint disease activity score and CRP, anti-CCP positivity was associated with EULAR response (OR=1.9;95% CI=1.2 to 2.9, p=0.007), but not rheumatoid factor (OR=1.0;95% CI=0.6 to 1.6, p=0.9). Anti-CCP positivity was also significantly associated with a higher ABA retention rate at 6 months. CONCLUSIONS: Real life efficacy of ABA in the ORA registry was similar as that reported in clinical trials. Anti-CCP positivity was associated with a better response to ABA, independently from disease activity.


Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Immunoconjugates/therapeutic use , Peptides, Cyclic/immunology , Abatacept , Aged , Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/pathology , Female , Health Status , Humans , Immunoconjugates/adverse effects , Joints/drug effects , Joints/pathology , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Registries , Severity of Illness Index , Treatment Outcome
7.
Osteoporos Int ; 23(12): 2855-61, 2012 Dec.
Article En | MEDLINE | ID: mdl-22349911

UNLABELLED: Bone mineral density (BMD; measured by DXA) changes were observed at all sites at 1 year in 146 patients with anorexia nervosa. Four independent factors accounted for the variation in BMD at the spine: duration of anorexia, bone-specific alkaline phosphatase (BAP), cross-linked carboxyterminal telopeptide region of type I collagen (ICTP), and triiodothyronine (T3). No change in BMD was observed from 1 to 2 years during follow-up. INTRODUCTION: The purpose of this study was to assess changes in BMD at 1 and 2 years in anorexia nervosa patients, and to explore the relationships between change in BMD and various clinical and biological parameters measured at the first visit. METHODS: BMD was measured in anorexia nervosa patients at inclusion, at 1-year follow-up (n = 146) and at 2-year follow-up (n = 89). RESULTS: Bone loss was observed at all sites at 1 year. When multivariate analyses were performed, four independent factors accounted for the variation in BMD at the spine: duration of anorexia nervosa, BAP, ICTP, and T3. At the total hip site, leptin level was the main factor accounting for the variation in BMD. Strong correlations were also observed between weight at 1 year and change in BMD at 2 years. At the 2-year follow-up, no significant change in BMD was observed at the spine or femoral neck. In patients who were no longer amenorrheic at 1 year, a significant improvement in BMD at 2 years was observed at the total hip (+1.2%, p = 0.02) and femoral neck (+3.7%, p = 0.02). Similarly, in patients with a body mass index >17 kg/m(2) at 1 year, an improvement in BMD at the total hip at 2 years was observed (+3%, p = 0.02) CONCLUSION: Bone loss in anorexia nervosa patients occurs at an early stage, and the factors influencing such are different at the spine and hip.


Anorexia Nervosa/complications , Osteoporosis/etiology , Absorptiometry, Photon , Adolescent , Adult , Alkaline Phosphatase/blood , Anorexia Nervosa/blood , Anorexia Nervosa/physiopathology , Biomarkers/blood , Bone Density/physiology , Collagen Type I/blood , Female , Femur Neck/physiopathology , Follow-Up Studies , Hip Joint/physiopathology , Humans , Lumbar Vertebrae/physiopathology , Middle Aged , Osteoporosis/blood , Osteoporosis/physiopathology , Peptides/blood , Risk Factors , Triiodothyronine/analogs & derivatives , Triiodothyronine/blood , Young Adult
8.
Ann Rheum Dis ; 70(7): 1251-6, 2011 Jul.
Article En | MEDLINE | ID: mdl-21515603

OBJECTIVES: To determine predictors of short-term radiographic progression in an inception cohort of patients with early arthritis. METHODS: Patients presenting with synovitis of at least two joints for 6 weeks to 6 months were included in the Etude et Suivi des POlyarthrites Indifferenciées Récentes (ESPOIR) cohort. Univariate analysis was used to determine the relationship between baseline variables and radiographic outcome (assessed by the modified total Sharp score (mTSS)) after 6 and 12 months. Stepwise multiple logistic regression was used to select independent predictive factors. The sensitivity and specificity of rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) at baseline in discriminating between erosive and non-erosive disease were determined by receiver operating characteristic (ROC) curves. RESULTS: From data available for 736 patients, radiographic progression at 6 months was independently predicted by baseline ACPA, human leucocyte antigen (HLA)-DRB1*01 and/or 04 genes, erythrocyte sedimentation rate and mTSS. Interestingly, the season of onset of the first symptoms was associated with the severity of early arthritis (OR 1.66, 95% CI 1.07 to 2.59, in winter and spring vs summer and autumn). Univariate analysis revealed similar results for season at 12 months (OR 1.68, 95% CI 1.20 to 2.37). The peak of the ROC curves for radiographic outcome occurred with ACPA and RF values similar to the cut-offs provided by manufacturers. CONCLUSION: The authors found the onset of arthritis symptoms during winter or spring associated with greater radiographic progression at 6 months for patients with early arthritis. These data could reinforce the role of environmental factors in the development and outcome of rheumatoid arthritis.


Arthritis/diagnosis , Seasons , Adult , Aged , Arthritis/diagnostic imaging , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/diagnostic imaging , Autoantibodies/blood , Biomarkers/blood , Blood Sedimentation , Disease Progression , Early Diagnosis , Epidemiologic Methods , Female , HLA-DR Antigens/genetics , HLA-DRB1 Chains , Humans , Male , Middle Aged , Peptides, Cyclic/immunology , Prognosis , Radiography , Rheumatoid Factor/blood , Synovitis/diagnostic imaging , Young Adult
9.
Arthritis Rheum ; 62(9): 2625-32, 2010 Sep.
Article En | MEDLINE | ID: mdl-20506353

OBJECTIVE: The risk of severe infection is a crucial factor in the assessment of the short-term risk:benefit ratio of biologic drugs in rheumatoid arthritis (RA). There is no increase in severe infections in RA patients treated with rituximab (RTX) in controlled trials, but this has not yet been assessed in daily practice. We undertook this study to investigate the occurrence of and risk factors for severe infections in off-trial patients using data from the AutoImmunity and Rituximab (AIR) registry. METHODS: The AIR registry was set up by the French Society of Rheumatology. The charts of patients with severe infections were reviewed. RESULTS: Of the enrolled patients, 1,303 had at least 1 followup visit at 3 months or later, with a mean ± SD followup period of 1.2 ± 0.8 years (1,629 patient-years). Eighty-two severe infections occurred in 78 patients (5.0 severe infections per 100 patient-years), half of them in the 3 months following the last RTX infusion. Multivariate analysis showed that chronic lung disease and/or cardiac insufficiency (odds ratio 3.0 [95% confidence interval 1.3-7.3], P = 0.01), extraarticular involvement (odds ratio 2.9 [95% confidence interval 1.3-6.7], P = 0.009), and low IgG level (<6 gm/liter) before initiation of RTX treatment (odds ratio 4.9 [95% confidence interval 1.6-15.2], P = 0.005) were significantly associated with increased risk of a severe infection. CONCLUSION: The rate of severe infections in current practice is similar to that reported in clinical trials. The risk factors for severe infections include chronic lung and/or cardiac disease, extraarticular involvement, and low IgG before RTX treatment. This suggests that serum IgG should be checked and the risk:benefit ratio of RTX discussed for patients found to have low levels of IgG.


Antibodies, Monoclonal/adverse effects , Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/drug therapy , Bacterial Infections/immunology , Registries , Agammaglobulinemia/immunology , Antibodies, Monoclonal, Murine-Derived , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/immunology , Bacterial Infections/complications , Contraindications , Female , Humans , Immunocompromised Host , Immunoglobulin G/blood , Male , Middle Aged , Risk Factors , Rituximab , Tumor Necrosis Factor-alpha/antagonists & inhibitors
10.
Vet Rec ; 164(14): 418-24, 2009 Apr 04.
Article En | MEDLINE | ID: mdl-19346540

This review assesses the evidence for the efficacy of therapies used in the management of osteoarthritis in dogs on the basis of papers published in peer-reviewed journals in English between 1985 and July 2007. Sixty-eight papers were identified and evaluated. They considered four alternative therapies, one use of functional food, two intra-articular agents, six nutraceutical agents, 21 pharmacological agents, two physical therapies, three surgical techniques and two combinations of weight control. There was a high level of comfort (strong evidence) for the efficacy of carprofen, firocoxib and meloxicam, and a moderate level of comfort for the efficacy of etodolac in modifying the signs of osteoarthritis. There was a moderate level of comfort for the efficacy of glycosaminoglycan polysulphate, licofelone, elk velvet antler and a functional food containing green-lipped mussel for the modification of the structures involved in the disease. There was weak or no evidence in support of the use of doxycycline, electrostimulated acupuncture, extracorporeal shockwave therapy, gold wire acupuncture, hyaluronan, pentosan polysulphate, P54FP (extract of turmeric), tiaprofenic acid or tibial plateau levelling osteotomy.


Dog Diseases/therapy , Osteoarthritis/veterinary , Animals , Anti-Bacterial Agents/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Complementary Therapies/methods , Complementary Therapies/veterinary , Dogs , Evidence-Based Practice , Osteoarthritis/therapy , Treatment Outcome
11.
BMJ ; 338: b421, 2009 Feb 23.
Article En | MEDLINE | ID: mdl-19237406

OBJECTIVE: To evaluate the impact of standardised consultations on patients with osteoarthritis of the knee. DESIGN: Open pragmatic cluster randomised controlled trial. SETTING: Primary care in France. PARTICIPANTS: 198 primary care rheumatologists, each of whom had to include two consecutive patients who met the American College of Rheumatology criteria for osteoarthritis of the knee. INTERVENTIONS: Standardised consultation was provided during three goal oriented visits (education on osteoarthritis and treatment management; information on physical exercises; information on weight loss) or usual care. MAIN OUTCOME MEASURES: Change in body weight and in time spent on physical exercises (Baecke index) at four months. RESULTS: 336 patients were included (154 allocated to standardised consultation and 182 to usual care). Nine patients were excluded because of lack of baseline data (standardised consultation, n=8; usual care, n=1). At four months, taking into account the clustering effect, the decrease in weight was greater in the standardised consultation group than in the usual care group (mean -1.11 (SD 2.49) kg v -0.37 (2.39) kg; P=0.007). The physical activity score was higher for the standardised consultation group than for the usual care group (mean 0.20 (0.65) v 0.04 (0.78); P=0.013). The standardised consultation and usual care groups did not differ in secondary outcomes, except for global assessment of disease activity (0-10 numeric scale: mean -1.66 (2.26) v -0.90 (2.48); P=0.003) and pain level (0-10 numeric scale: mean -1.65 (2.32) v -1.18 (2.58); P=0.04). CONCLUSIONS: A structured consultation programme for patients with osteoarthritis of the knee resulted in short term improvement in weight loss and time spent on physical activity. TRIAL REGISTRATION: Clinical trials NCT00462319.


Osteoarthritis, Knee/therapy , Aged , Analgesics/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Cluster Analysis , Exercise Therapy , Female , France , Guideline Adherence , Humans , Male , Middle Aged , Obesity/complications , Obesity/prevention & control , Patient Satisfaction , Practice Guidelines as Topic , Primary Health Care , Sample Size , Treatment Outcome , Weight Loss
12.
Rheumatology (Oxford) ; 47(11): 1698-703, 2008 Nov.
Article En | MEDLINE | ID: mdl-18794185

OBJECTIVES: Several anti-TNF-alpha prescription guidelines in RA have been published, among which those issued by the British (BSR) and French (SFR) Societies for Rheumatology in 2005 are the most comprehensive. Objectives of the PRISME II survey were to assess and compare eligibility for anti-TNF-alpha therapy of RA patients consulting their usual rheumatologist according to (i) the SFR and BSR guidelines and (ii) the rheumatologist's opinion. METHODS: PRISME II was a postal, cross-sectional, observational survey proposed to all office-based rheumatologists practising in France in 2005. Rheumatologists were to include three consecutive consulting anti-TNF-alpha-naïve RA patients. Disease activity was assessed using the disease activity score 28 (DAS28). Structural damage progression was estimated based on the reading by the usual rheumatologist. The factors determining eligibility in the rheumatologists' opinion were identified by a logistic regression analysis. RESULTS: Four hundred and thirty-four rheumatologists included 1132 patients. Ongoing RA structural progression was reported for 41% of the patients. According to the SFR and BSR criteria, 64 patients (7.0%) and 10 patients (0.9%), respectively, were eligible for anti-TNF-alpha therapy, while 10% were deemed eligible according to the rheumatologists' opinion. Determinants of eligibility according to the rheumatologists were: high disease activity (DAS28 >5.1), ongoing structural progression and elevated daily corticosteroid intake. These three determinants feature in the SFR guideline. CONCLUSIONS: The proportion of RA patients eligible for anti-TNF-alpha therapy varies greatly according to the BSR or SFR guidelines. In France, there is a remarkable convergence between rheumatologists' opinion and SFR guideline regarding the main factors to consider for initiation of an anti-TNF-alpha therapy.


Arthritis, Rheumatoid/drug therapy , Eligibility Determination , Immunosuppressive Agents/therapeutic use , Rheumatology , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Aged , Antirheumatic Agents/therapeutic use , Female , France , Health Planning Guidelines , Humans , Male , Methotrexate/therapeutic use , Middle Aged , Societies, Medical , Treatment Failure , United Kingdom
14.
Clin Microbiol Infect ; 14(2): 183-6, 2008 Feb.
Article En | MEDLINE | ID: mdl-18076664

This study investigated the long-term outcome of patients with tuberculosis (TB) as a complication of tumour necrosis factor (TNF)-alpha blocker therapy. All TB cases (n = 21) complicating TNF-alpha blocker therapy from French university hospitals were collated between January 2000 and September 2002. Outcome was assessed via a postal questionnaire during September 2005. The mortality rate after 4 years was 4.8%, and one patient had relapsed and six (29%) patients had recommenced TNF-alpha antagonist treatment, after appropriate anti-TB therapy, without reactivation. These data support the concept that TNF-alpha antagonists can be restarted in TB patients provided that adequate anti-TB treatment has been completed.


Antibodies, Monoclonal/adverse effects , Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/drug therapy , Tuberculosis/chemically induced , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Aged , Aged, 80 and over , Antibodies, Monoclonal/therapeutic use , Antirheumatic Agents/therapeutic use , Antitubercular Agents/therapeutic use , Arthritis, Rheumatoid/complications , Female , Follow-Up Studies , France/epidemiology , Humans , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Infliximab , Male , Middle Aged , Surveys and Questionnaires , Treatment Outcome , Tuberculosis/drug therapy , Tuberculosis/mortality
15.
Scand J Rheumatol ; 36(5): 373-7, 2007.
Article En | MEDLINE | ID: mdl-17963167

OBJECTIVE: To compare the activities of cathepsin B (EC 3.4.22.1) and L (EC 3.4.22.15), calpain (EC 3.4.22.17), and dipeptidyl peptidase (EC 3.4.14.5 or DPP IV or CD26) in synovial membrane from patients with rheumatoid arthritis (RA), osteoarthritis (OA), and post-traumatic joint injury (PT). METHODS: Forty RA patients were divided into two groups on the basis of surgical procedure: the RAs group comprised 18 patients requiring surgical synovectomy; the RAr group comprised 22 patients requiring a total joint replacement or arthrodesis. A third group (the OA group) comprised 19 OA patients while six patients with post-traumatic joint injury were included in the fourth group (the PT group). Cathepsin and calpain activity was assessed using a Cobas Fara II centrifugal analyser. DPP IV activity was determined kinetically using a fluorogenic substrate. RESULTS: RAs patients were significantly younger than RAr patients, and the mean duration of RA was shorter in the RAs group than in the RAr group. Cathepsin and calpain activity in synovial membrane was higher in RA and OA patients than in the control group, but no statistical difference was observed between RA and OA. However, cathepsin, calpain, and DPP IV synovial activity was significantly higher in the RAs group than in either the OA or the PT group. CONCLUSION: Our results show that proteinase activity tends to be higher in joints with early synovitis in RA, and suggest that these enzymes are not all involved at the same stage of the disease.


Arthritis, Rheumatoid/enzymology , Calpain/metabolism , Cathepsin B/metabolism , Cathepsins/metabolism , Cysteine Endopeptidases/metabolism , Dipeptidyl Peptidase 4/metabolism , Osteoarthritis/enzymology , Synovial Membrane/enzymology , Adult , Age Factors , Aged , Cathepsin L , Female , Humans , Kinetics , Male , Middle Aged
16.
Ann Dermatol Venereol ; 134(4 Pt 1): 337-42, 2007 Apr.
Article Fr | MEDLINE | ID: mdl-17483752

BACKGROUND: TNFalpha blockers have recently extended the therapeutic arsenal available in dermatology. However, dermatologists must be informed of their potential adverse dermatological effects. While the chief adverse effect of TNFalpha blockers is risk of infection, cutaneous adverse effects have not yet been clearly elucidated and publications on this topic are few and far between. The aim of our study is to report various dermatological problems noted during treatment with TNFalpha blockers. PATIENTS AND METHODS: This was a retrospective study of patient files. The study population comprised patients receiving TNFalpha blockers and presenting cutaneous reaction, and seen in the dermatology department between August 2001 and December 2004. RESULTS: Eleven patients were included. The following cutaneous reactions were seen: delayed skin rash (1 case), lupus syndrome (1 case), cutaneous vasculitis (2 cases), palmoplantar pustulosis (2 cases), psoriasis vulgaris (1 case), atopic dermatitis (1 case), lichenoid rash (1 case), purpuric capillaritis (1 case) and melanoma (1 case). DISCUSSION: The cutaneous manifestations seen represented a wide range of different clinical pictures. Dermatologists must be aware of these potential adverse effects. Future improvement of knowledge of the physiopathological mechanisms as well as the institution of prospective cohort studies should provide clearer guidance on the management of such symptoms.


Skin Diseases/chemically induced , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adult , Aged , Antibodies, Monoclonal/adverse effects , Etanercept , Exanthema/chemically induced , Fasciitis, Plantar/chemically induced , Female , Humans , Immunoglobulin G/adverse effects , Infliximab , Lupus Erythematosus, Systemic/chemically induced , Male , Middle Aged , Receptors, Tumor Necrosis Factor , Retrospective Studies , Vasculitis/chemically induced
17.
Rheumatology (Oxford) ; 45(9): 1121-4, 2006 Sep.
Article En | MEDLINE | ID: mdl-16510526

OBJECTIVE: Some studies have highlighted the potential benefits of switching from infliximab to etanercept, or after failure of one or the other treatment. To our knowledge, no study has assessed the potential benefits of using the three anti-TNF-alpha agents that are currently available. The objective of this retrospective study was to assess the response to treatment in RA patients who had received the three anti-TNF-alpha agents, namely infliximab, etanercept and adalimumab. METHODS: Among a cohort of 364 patients undergoing biological treatments since the year 2000, 284 had been treated with only one anti-TNF-alpha agent. Our assessment focused on the records of 70 patients who had received at least two anti-TNF-alpha agents. Twenty of the 70 patients had received all three anti-TNF-alpha agents (infliximab, etanercept and adalimumab). Effectiveness was assessed using the 28-joint Disease Activity Score (DAS28), and adverse events were reported for each anti-TNF-alpha treatment. RESULTS: Of the 70 patients who had received two anti-TNF-alpha agents, 32 had switched from an antibody to a soluble receptor; 45% of them had a good clinical response to the soluble receptor. Thirty patients had switched from a soluble receptor to an antibody; 45% of them had a good clinical response to the antibody. Only eight patients had switched from an antibody to another antibody with an efficiency score of 33%. Of the 20 patients who had received three anti-TNF-alpha agents, seven had stopped receiving the third anti-TNF-alpha agent due to lack of effectiveness. In this group of non-responders to the third anti-TNF-alpha treatment, all patients except one had stopped receiving the two previous anti-TNF-alpha agents, without adverse events, for lack of effectiveness. These patients were deemed resistant to anti-TNF-alpha therapy. CONCLUSIONS: Resistance to anti-TNF-alpha agents is rare. The lack of effectiveness of a soluble receptor and of one of the anti-TNF-alpha antibodies predicts the lack of effectiveness of the third anti-TNF-alpha treatment.


Arthritis, Rheumatoid/drug therapy , Immunologic Factors/administration & dosage , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adalimumab , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Drug Administration Schedule , Drug Therapy, Combination , Etanercept , Female , Humans , Immunoglobulin G/administration & dosage , Immunoglobulin G/therapeutic use , Immunologic Factors/therapeutic use , Infliximab , Male , Middle Aged , Receptors, Tumor Necrosis Factor/administration & dosage , Receptors, Tumor Necrosis Factor/therapeutic use , Retrospective Studies , Statistics, Nonparametric , Treatment Failure
18.
Ann Rheum Dis ; 65(1): 45-50, 2006 Jan.
Article En | MEDLINE | ID: mdl-15994280

OBJECTIVE: To elaborate a clinical practice decision tree for the choice of the first disease modifying antirheumatic drug (DMARD) for untreated rheumatoid arthritis of less than six months' duration. METHODS: Four steps were employed: (1) review of published reports on DMARD efficacy against rheumatoid arthritis; (2) inventory of the information available to guide DMARD choice; (3) selection of the most pertinent information by 12 experts using a Delphi method; and (4) choice of DMARDs in 12 clinical situations defined by items selected in step 3 (28 joint disease activity score (DAS 28): < or =3.2; >3.2 and < or =5.1; >5.1; rheumatoid factor status (positive/negative); structural damage (with/without)-that is, 3 x 2 x 2). Thus, multiplied by all the possible treatment pairs, 180 scenarios were obtained and presented to 36 experts, who ranked treatment choices according to the Thurstone pairwise method. RESULTS: Among the 77 items identified, 41 were selected as pertinent to guide the DMARD choice. They were reorganised into five domains: rheumatoid arthritis activity, factors predictive of structural damage; patient characteristics; DMARD characteristics; physician characteristics. In the majority of situations, the two top ranking DMARD choices were methotrexate and leflunomide. Etanercept was an alternative for these agents when high disease activity was associated with poor structural prognosis and rheumatoid factor positivity. CONCLUSIONS: Starting with simple scenarios and using the pairwise method, a clinical decision tree could be devised for the choice of the first DMARD to treat very early rheumatoid arthritis.


Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Decision Trees , Biomarkers/blood , Choice Behavior , France , Humans , Practice Guidelines as Topic , Rheumatoid Factor/blood , Severity of Illness Index , Societies, Medical , Treatment Outcome
19.
Rev Mal Respir ; 22(4): 667-71, 2005 Sep.
Article Fr | MEDLINE | ID: mdl-16294184

INTRODUCTION: Inflammatory arthropathies are rare complications of cystic fibrosis (CF). We describe three cases of rheumatoid arthritis (RA) occurring in patients with this disease. OBSERVATIONS: Among the 100 patients under the care of the adult CF centre in Lille 3 presented with RA. This developed at the ages of 17, 44 and 19 years with a FEV1 of 53%, 42% and 94% respectively. They were 2 women and 1 man, with CFTR gene mutation delta F508 (1 homozygote and 2 heterozygotes) and positive sweat tests. They were colonised with Staphylococcus aureus, and rheumatoid factor and/or anti CCP antibodies were positive. The appearance and progression of RA were associated with exacerbations of bronchial infection and deterioration of respiratory function. In 2 patients the RA was continuously progressive despite intensive treatment involving high dose cortico-steroids, methotrexate (ineffective) followed by leflunomide (complicated by intractable respiratory infection). CONCLUSION: There is an increased incidence of RA in our patient population with CF. The new serum markers of RA including anti CCP are of diagnostic interest. The evolution of the two diseases is related and seems to be dependent on the level of infection leading to therapeutic problems.


Arthritis, Rheumatoid/complications , Cystic Fibrosis/complications , Adult , Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/diagnosis , Biomarkers/blood , Cystic Fibrosis/blood , Cystic Fibrosis/diagnosis , Female , Humans , Immunologic Factors/blood , Male , Middle Aged , Rheumatoid Factor/blood
20.
Scand J Infect Dis ; 37(6-7): 532-3, 2005.
Article En | MEDLINE | ID: mdl-16012023

We report a case of Streptobacillus moniliformis polyarthritis mimicking a rheumatoid arthritis, in a pet shop employee. In culture of fluid joint growth a curious Gram-negative bacillus was identified by polymerase chain reaction as Streptobacillus moniliformis. The outcome was good after surgical debridment and rifampin-clindamycin combination during 4 weeks.


Arthritis, Infectious/diagnosis , Arthritis, Infectious/microbiology , Arthritis, Rheumatoid/diagnosis , Rat-Bite Fever/diagnosis , Arthritis, Infectious/drug therapy , Arthritis, Infectious/surgery , Diagnosis, Differential , Female , Humans , Middle Aged , Streptobacillus/isolation & purification
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