Rheumatoid Arthritis: Quartier P

Quartier P. · No affiliation provided · Joint Bone Spine. · Pubmed #17174585 No free full text.

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Quartier P, Prieur AM. · Unit d'immunologie-hématologie et rhumatologie pédiatriques, Centre de référence national labellisé Arthrites juvéniles, hôpital Necker-Enfants malades, 75743 Paris. · Rev Prat. · Pubmed #17717939 No free full text.

Abstract: Immunosuppressants, including methotrexate and more recently anti-TNFalpha, have modified the prognosis of the most severe forms juvenile idiopathic arthritis. However, the therapeutic management is still challenging and adjuvant therapies, including physiotherapy, surgery, or even bisphosphonates and growth hormone, are still widely used to limit the negative impact of an extended general corticotherapy.

Quartier P, Prieur AM. · Unité d'immunologie-hématologie et rhumatologie pédiatriques, Centre de référence national labellisé "Arthrites juvéniles , hôpital Necker-Enfants malades, 75743 Paris 15. · Rev Prat. · Pubmed #17691258 No free full text.

Abstract: Juvenile idiopathic arthritis (JIA), formerly know as juvenile chronic arthritis, is a broad term encompassing several disorders starting before the age of 16. It is characterized by arthritis lasting more than 6 weeks, of unknown etiology, usually persisting for six month initially. Approximately 1 in 5 000 children are affected in France. Of the various distinguishable clinical forms, oligoarticular JIA is the most frequent one. It is characterized by an involvement of up to 4 joints during the first 6 months and is mostly observed in females. The prognosis may be further complicated by the presence of uveitis, associated with an insidious progression. In systemic JIA (also called Still's disease) as well as in some polyarticular forms, with or without rheumatoid factor, inflammation may continue in adulthood. Severe polyarticular involvement or hip involvement may be associated with a poor functional prognosis.

Ruperto N, Lovell DJ, Quartier P, Paz E, Rubio-Pérez N, Silva CA, Abud-Mendoza C, Burgos-Vargas R, Gerloni V, Melo-Gomes JA, Saad-Magalhães C, Sztajnbok F, Goldenstein-Schainberg C, Scheinberg M, Penades IC, Fischbach M, Orozco J, Hashkes PJ, Hom C, Jung L, Lepore L, Oliveira S, Wallace CA, Sigal LH, Block AJ, Covucci A, Martini A, Giannini EH, Anonymous00184, Anonymous00185. · IRCCS G Gaslini, PRINTO, Genoa, Italy. · Lancet. · Pubmed #18632147 No free full text.

Abstract: BACKGROUND: Some children with juvenile idiopathic arthritis either do not respond, or are intolerant to, treatment with disease-modifying antirheumatic drugs, including anti-tumour necrosis factor (TNF) drugs. We aimed to assess the safety and efficacy of abatacept, a selective T-cell costimulation modulator, in children with juvenile idiopathic arthritis who had failed previous treatments. METHODS: We did a double-blind, randomised controlled withdrawal trial between February, 2004, and June, 2006. We enrolled 190 patients aged 6-17 years, from 45 centres, who had a history of active juvenile idiopathic arthritis; at least five active joints; and an inadequate response to, or intolerance to, at least one disease-modifying antirheumatic drug. All 190 patients were given 10 mg/kg of abatacept intravenously in the open-label period of 4 months. Of the 170 patients who completed this lead-in course, 47 did not respond to the treatment according to predefined American College of Rheumatology (ACR) paediatric criteria and were excluded. Of the patients who did respond to abatacept, 60 were randomly assigned to receive 10 mg/kg of abatacept at 28-day intervals for 6 months, or until a flare of the arthritis, and 62 were randomly assigned to receive placebo at the same dose and timing. The primary endpoint was time to flare of arthritis. Flare was defined as worsening of 30% or more in at least three of six core variables, with at least 30% improvement in no more than one variable. We analysed all patients who were treated as per protocol. This trial is registered, number NCT00095173. FINDINGS: Flares of arthritis occurred in 33 of 62 (53%) patients who were given placebo and 12 of 60 (20%) abatacept patients during the double-blind treatment (p=0.0003). Median time to flare of arthritis was 6 months for patients given placebo (insufficient events to calculate IQR); insufficient events had occurred in the abatacept group for median time to flare to be assessed (p=0.0002). The risk of flare in patients who continued abatacept was less than a third of that for controls during that double-blind period (hazard ratio 0.31, 95% CI 0.16-0.95). During the double-blind period, the frequency of adverse events did not differ in the two treatment groups. Adverse events were recorded in 37 abatacept recipients (62%) and 34 (55%) placebo recipients (p=0.47); only two serious adverse events were reported, both in controls (p=0.50). INTERPRETATION: Selective modulation of T-cell costimulation with abatacept is a rational alternative treatment for children with juvenile idiopathic arthritis. FUNDING: Bristol-Myers Squibb.

Lequerré T, Quartier P, Rosellini D, Alaoui F, De Bandt M, Mejjad O, Kone-Paut I, Michel M, Dernis E, Khellaf M, Limal N, Job-Deslandre C, Fautrel B, Le Loët X, Sibilia J, Anonymous00361, Anonymous00362. · Rheumatology Department, Rouen University Hospital & Inserm 905, 76031 Rouen, France. · Ann Rheum Dis. · Pubmed #17947302 No free full text.

Abstract: BACKGROUND: Anakinra treatment has been reported to be effective in some patients with systemic-onset juvenile idiopathic arthritis (SoJIA) or adult-onset Still disease (AoSD). OBJECTIVES: To assess the efficacy and the safety of anakinra treatment in SoJIA and AoSD. METHODS: SoJIA and AoSD patients were treated with anakinra (1-2 mg/kg/day in children, 100 mg/day in adults); we analysed its effect on fever, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels, numbers of swollen and tender joints, the assessment of disease activity (by physician and parent/patient) and pain (by parent/patient), and American College of Rheumatology (ACR) pediatric core set criteria for JIA activity. RESULTS: A total of 35 patients were included, 20 with SoJIA and 15 with AoSD. Their mean age (range) at the onset of treatment was 12.4 (3-23) and 38.1 (22-62) years, respectively; disease duration was 7.0 (1-16) and 7.8 (2-27) years, respectively. Active arthritis was present in all cases but one. Of the 20 SoJIA patients, 5 achieved ACR 50% improvement in symptoms (ACR50) response criteria at 6 months. Steroid dose had been decreased by 15% to 78% in 10 cases. A total of 11 of the 15 AoSD patients achieved at least a 50% improvement for all disease markers (mean follow-up: 17.5 (11-27) months). Steroids had been stopped in two cases and the dose was decreased by 45% to 95% in 12 patients. Two patients stopped anakinra due to severe skin reaction, and two patients due to infection: one visceral leishmaniasis and one varicella. CONCLUSION: Anakinra was effective in most AoSD patients, but less than half SoJIA patients achieved a marked and sustained improvement.

Quartier P, Taupin P, Bourdeaut F, Lemelle I, Pillet P, Bost M, Sibilia J, Koné-Paut I, Gandon-Laloum S, LeBideau M, Bader-Meunier B, Mouy R, Debré M, Landais P, Prieur AM. · Hôpital Necker-Enfants Malades, Paris, France. · Arthritis Rheum. · Pubmed #12687553 links to  free full text

Abstract: OBJECTIVE: To assess the efficacy of etanercept in patients with juvenile idiopathic arthritis (JIA), and to assess the tolerance of these patients to etanercept. METHODS: All JIA patients with active chronic polyarthritis, who were first treated with etanercept between November 1999 and June 2001 in 18 French centers because of poor response or intolerance to methotrexate, were included in this open-label, prospective, multicenter study. A standardized questionnaire was sent to the treating physicians. We assessed the validated international core-set score for JIA activity every 3 months and performed an intent-to-treat analysis. We also compared the risk of treatment failure in patients defined as having systemic-onset, oligoarticular-onset, or polyarticular-onset JIA. RESULTS: Sixty-one patients were enrolled and were followed up for a median of 13 months. Treatment had to be stopped in 1 patient who became pregnant and in 12 patients due to severe side effects, including neurologic or psychiatric disorders, retrobulbar optic neuropathy, major weight gain, severe infection, cutaneous vasculitis with systemic symptoms, hemorrhagic diarrhea, uveitis flare, and pancytopenia. All of these side effects disappeared after discontinuation of etanercept. Crohn's disease was subsequently diagnosed in 1 child. Scores improved by > or =30% in 73% of patients after 3 months, but this proportion decreased to 39% after 12 months. The response rate was significantly lower in patients with systemic-onset JIA than in those with oligoarticular- or polyarticular-onset JIA. CONCLUSION: Treatment of JIA with etanercept may be associated with a wide spectrum of severe side effects. Although most patients initially respond to etanercept, this initial response is not always followed by sustained improvement over longer periods of time. In addition, the higher rate of treatment failure in the group with systemic-onset JIA indicates that these patients in particular may require alternative treatments.

Quartier P. · Centre de référence national desmaladies rares Arthrites Juvéniles, AP-HP, Unité d'Immuno-Hématologie et Rhumatologie Pédiatrique, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, 75015 Paris, France. <> · Arch Pediatr. · Pubmed #18582783 No free full text.

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Simon D, Prieur AM, Quartier P, Charles Ruiz J, Czernichow P. · Department of Pediatric Endocrinology, Robert Debré Teaching Hospital, 75019 Paris, France. · J Clin Endocrinol Metab. · Pubmed #17488793 links to  free full text

Abstract: CONTEXT: Long-term glucocorticoid therapy adversely affects growth and body composition in children with juvenile idiopathic arthritis (JIA). In previous studies, recombinant human GH (rhGH) halted the progression of these complications without inducing catch-up growth. OBJECTIVES: The objective of the study was to evaluate the impact on growth and body composition of rhGH started early after glucocorticoid initiation and to record adverse effects in children with JIA. DESIGN: This is a 3-yr randomized controlled study. SETTING: This study was conducted in a teaching hospital. PATIENTS: Thirty children, 12-15 months into glucocorticoid therapy for severe JIA, were enrolled. INTERVENTION: Patients received rhGH (0.46 mg/kg.wk) in daily sc injections (n = 15) or no rhGH therapy (n = 15) for 3 yr. MAIN OUTCOME MEASURE: Difference in height sd score (SDS) change between the two groups was assessed. Height velocity, body composition, and oral glucose tolerance were evaluated yearly. RESULTS: Mean height SDS increase was larger with rhGH (+0.37 +/- 1.5 SDS) than without (-0.96 +/- 1.2 SDS) (P = 0.04). Mean height velocity returned to normal within the first year of rhGH treatment and remained normal thereafter. Mean lean mass increase was greater with rhGH treatment (+7.3 +/- 2.9 kg vs. +4.4 +/- 2.8 kg; P = 0.03). Fat mass and bone mineralization were not significantly different in the two groups. Fasting serum insulin increased significantly in rhGH-treated patients (5.2 +/- 16 mIU/liter) compared with untreated controls (-2.3 +/- 5 mIU/liter) (P = 0.04); fasting glycemia was unchanged. CONCLUSIONS: rhGH started early in the course of JIA preserved normal growth velocity and height. Although rhGH was well tolerated, carbohydrate metabolism should be monitored closely.

Chédeville G, Quartier P, Miranda M, Brauner R, Prieur AM. · Unité d'Immuno-Hématologie-Rhumatologie Pédiatrique, hôpital Necker-Enfants-Malades, 149 rue de Sèvres, 75743 Paris cedex 15, France. · Joint Bone Spine. · Pubmed #16087383 No free full text.

Abstract: OBJECTIVE: To assess changes in growth parameters associated with the response to methotrexate (MTX) therapy in pre-pubertal children with juvenile idiopathic arthritis (JIA) and who had not been treated with steroids. METHODS: We enrolled 27 pre-pubertal children with JIA who had been treated with MTX but not with steroids. The children were considered to have responded to treatment if the number of joints with active disease decreased by at least 50% 1 year after treatment initiation. We compared growth parameters (height, growth rate, weight and body mass index (BMI)) in responders and non-responders. RESULTS: Twenty-one children (77.8%) responded to MTX therapy. The growth parameters were similar in the responders and non-responders before the onset of treatment. After 1 year, height (P=0.025), growth rate (P=0.03), weight (P=0.007) and BMI (P=0.05) increased significantly in the responder group, but not in the non-responder group. This increase was maintained for growth rate and weight after 2 and 3 years of treatment. After 1 year, height (P=0.023) and growth rate (P=0.0009) were significantly higher in the responders than in the non-responders, and these differences were still significant after 3 years (P=0.01 and P=0.033, respectively). CONCLUSION: In pre-pubertal children with JIA, a clinical response to MTX therapy is associated with a significant increase in growth parameters.

Tas SW, Quartier P, Botto M, Fossati-Jimack L. · Rheumatology Section, Division of Medicine, Faculty of Medicine, Hammersmith Campus, Imperial College, Du Cane Road, London W12 0NN, UK. · Ann Rheum Dis. · Pubmed #16014673 links to  free full text

Abstract: BACKGROUND: It has been suggested that defective handling of apoptotic cells by macrophages plays a key role in the development of systemic lupus erythematosus (SLE). The relative contribution of intrinsic defects and serum factors remains controversial. OBJECTIVE: To compare monocytes from SLE patients, patients with rheumatoid arthritis, and healthy controls for their ability to differentiate in vitro into macrophages and to bind/engulf apoptotic cells. METHODS: Peripheral blood derived monocytes from healthy donors or from patients with SLE or rheumatoid arthritis were allowed to differentiate into macrophages. The in vitro uptake of apoptotic cells by macrophages was evaluated by a flow cytometry assay that allowed discrimination between binding and internalisation. RESULTS: Monocytes from SLE and rheumatoid patients showed a striking defect in adherence to plastic compared with healthy donors. Absence or heat inactivation of serum resulted in a reduction in the binding and engulfment of apoptotic cells by macrophages. Macrophages from rheumatoid and SLE patients had similar percentages of apoptotic cells bound to their surface compared with normal controls. However, macrophages from SLE patients showed a significant defect in the internalisation of apoptotic cells compared with those from healthy controls, even in the presence of normal human serum. CONCLUSIONS: Monocytes from patients with SLE and rheumatoid arthritis have a similar defect in their capacity to adhere to plastic. However, only macrophages from SLE patients showed an impaired ability to engulf apoptotic cells, which indicates that an intrinsic cellular defect may be responsible for this phenomenon.

De Kleer IM, Brinkman DM, Ferster A, Abinun M, Quartier P, Van Der Net J, Ten Cate R, Wedderburn LR, Horneff G, Oppermann J, Zintl F, Foster HE, Prieur AM, Fasth A, Van Rossum MA, Kuis W, Wulffraat NM. · Paediatric BMT unit, Suite KC 03.063, University Medical Centre Utrecht, PO box 85090, 3508 AB Utrecht, Netherlands. · Ann Rheum Dis. · Pubmed #15361393 links to  free full text

Abstract: OBJECTIVE: To evaluate the safety and efficacy of autologous stem cell transplantation (ASCT) for refractory juvenile idiopathic arthritis (JIA). DESIGN: Retrospective analysis of follow up data on 34 children with JIA who were treated with ASCT in nine different European transplant centres. Rheumatological evaluation employed a modified set of core criteria. Immunological reconstitution and infectious complications were monitored at three month intervals after transplantation. RESULTS: Clinical follow up ranged from 12 to 60 months. Eighteen of the 34 patients (53%) with a follow up of 12 to 60 months achieved complete drug-free remission. Seven of these patients had previously failed treatment with anti-TNF. Six of the 34 patients (18%) showed a partial response (ranging from 30% to 70% improvement) and seven (21%) were resistant to ASCT. Infectious complications were common. There were three cases of transplant related mortality (9%) and two of disease related mortality (6%). CONCLUSIONS: ASCT in severely ill patients with JIA induces a drug-free remission of the disease and a profound increase in general wellbeing in a substantial proportion of patients, but the procedure carries a significant mortality risk. The following adjustments are proposed for future protocols: (1) elimination of total body irradiation from the conditioning regimen; (2) prophylactic administration of antiviral drugs and intravenous immunoglobulins until there is a normal CD4+ T cell count.

Wulffraat NM, Haas PJ, Frosch M, De Kleer IM, Vogl T, Brinkman DM, Quartier P, Roth J, Kuis W. · Department of Paediatric Immunology, Wilhelmina Children's Hospital, University Medical Centre Utrecht, The Netherlands. · Ann Rheum Dis. · Pubmed #12594109 links to  free full text

Abstract: OBJECTIVES: To determine whether myeloid related proteins (MRP8/MRP14), a complex of two S100 proteins related to neutrophil and monocyte activation, might be used as a marker for disease activity, and as an early indicator of relapse in juvenile idiopathic arthritis. PATIENTS AND METHODS: A group of 12 patients who underwent an autologous haematopoietic stem cell transplantation (ASCT) for refractory juvenile idiopathic arthritis (JIA) were studied. MRP8/MRP14 serum concentrations were determined by a sandwich enzyme linked immunosorbent assay (ELISA) as described. Improvement from baseline was described by a definition of improvement employing a core set of criteria as detailed previously by Giannini. RESULTS: After ASCT, MRP8/MRP14 serum concentrations in JIA showed a positive correlation with the Child Health Assessment Questionnaire (CHAQ; r=0.80) and erythrocyte sedimentation rate (r=0.45), but not with the total leucocyte count (r=0.26). Mean MRP8/MRP14 serum concentrations dropped markedly in the first three months after ASCT (p=0.0039) and clinical parameters of disease activity such as CHAQ markedly improved (p=0.0039). During a transient relapse there was an increase in MRP8/MRP14. CONCLUSIONS: MRP8/MRP14 serum concentration can be used as a marker for disease activity in patients who receive an ASCT for refractory JIA. This indicates a role of macrophage activation in the pathogenesis of JIA. The occurrence of MAS in three patients in this study was not preceded by significant changes in MRP8/MRP14 concentration.

Pouchot J, Larbre JP, Lemelle I, Sommelet D, Grouteau E, David L, Duquesne A, Deslandre CJ, Koné Paut I, Pillet P, Goumy L, Barbier C, Guyot MH, Mazingue F, Laloum SG, Fischbac M, Quartier P, Guyot C, Jean S, Legall E, Plouvier E, Bost M, de Lumley L, Brégeon C, Guillemin F, Coste J, Prieur AM, Anonymous00241. · Internal Medicine Department, Médecine Interne, Hĵpital Louis Mourier, 178, rue des Renoullers, Colombes, France. · Joint Bone Spine. · Pubmed #12477231 No free full text.

Abstract: OBJECTIVES: To translate, cross-culturally adapt, and validate the functional disability tool Childhood Health Assessment Questionnaire (CHAQ), a variant of the Health Assessment Questionnaire (HAQ), in children with juvenile idiopathic arthritis (JIA). CHILDREN AND METHODS: The disability index is the mean of the scores on the eight domains of the CHAQ and can range from 0 (no disability) to 3 (maximum disability). The CHAQ was first translated into French and adapted, then validated in a multicenter cross-sectional study in 306 children with JIA (systemic onset, 23%; polyarticular onset, 22%; extended oligoarticular subtype, 25%; and persistent oligoarticular subtype, 30%). RESULTS: Overall CHAQ scores discriminated between the four JIA subtypes (systemic: 1.1 +/- 0.9; polyarticular: 0.8 +/- 0.7, extended oligoarticular 0.8 +/- 0.7, and persistent oligoarticular: 0.4 +/- 0.5 [P < 0.0001]). Reproducibility evaluated by test-retest at a 7-day interval was excellent (intraclass coefficient, 0.91), as was agreement between the Parent's and Children's versions of the questionnaire (intraclass coefficient, 0.89). Significant correlations were found between the overall CHAO score and variables reflecting disease severity (joint counts, physician's and parent's global assessments, and erythrocyte sedimentation rate), indicating excellent convergent validity of the tool. CONCLUSION: The French version of the CHAQ displays good psychometric characteristics, although its sensitivity to change remains to be established. The French version of the CHAO should prove useful in international studies and can be expected to be helpful for monitoring individual patients with JIA.

Pouchot J, Ruperto N, Lemelle I, Sommelet D, Grouteau E, David L, Duquesne A, Job Deslandre C, Kone Paut I, Pillet P, Goumy L, Barbier C, Guyot MH, Mazingue F, Gandon Laloum S, Fischbach M, Quartier P, Guyot C, Jean S, Le Gall E, Plouvier E, Bost M, de Lumley L, LePlège A, Larbre JP, Guillemin F, Coste J, Landgraf JM, Prieur AM, Anonymous00066. · Service de Médecine Interne, Hôpital Louis Mourier, Colombes, France. · Clin Exp Rheumatol. · Pubmed #11510333 No free full text.

Abstract: We report the results of the cross-cultural adaptation and validation into the French language of two health status instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health related quality of life instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. Five hundred children were enrolled including 306 patients with JIA classified into systemic (23%), polyarticular (22%), extended oligoarticular (25%), and persistent oligoarticular (30%) subtypes, and 194 healthy children. Both instruments were reliable with intra-class correlation (ICC) coefficients for the test-retest procedure of 0.91 for the CHAQ, and 0.87 and 0.89 for the physical and psychosocial summary scores of CHQ, respectively. Agreement between parents and children evaluated for the CHAQ was high with an ICC of 0.89 for the disability index; weighted kappa coefficients for the 8 domains ranged from 0.61 to 0.72. Convergent validity was demonstrated by significant correlations with the JIA core set of variables (physician and parent global assessment, scores for active joints and joints with limited range of motion, erythrocyte sedimentation rate) for both instruments. Both CHAQ and CHQ discriminated between healthy and JIA children, but only the disease specific CHAQ questionnaire discriminated clearly between the 4 JIA subtypes. In conclusion, the French versions of the CHAQ and the CHQ are reliable, and valid health assessment questionnaires to be used in children suffering from JIA.

Quartier P, Prieur AM, Fischer A. · No affiliation provided · Lancet. · Pubmed #10359443 No free full text.

This publication has no abstract.