Methotrexate in juvenile idiopathic arthritis: answers and questions.
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Antirheumatic Agents↗
Biomedical subjects
A Ravelli
Publications and source records attributed to A Ravelli.
Marked and sustained improvement two years after autologous stem cell transplantation in a girl with systemic sclerosis.
Autologous transplantation of hematopoietic stem cells has recently been proposed as a possible treatment for autoimmune diseases that are associated with a very severe prognosis. A 12-year-old girl who, since 4 years of age, had systemic sclerosis with progressive pulmonary involvement underwent autologous peripheral blood-derived stem cell transplantation (aPBSCT) using CD34+ selection, cyclophosphamide, and the infusion of the monoclonal antibody CAMPATH-1G. Following transplantation, in the absence of any treatment other than symptomatic therapy, the patient's exertional dyspnea and alveolitis disappeared and she experienced a marked improvement in skin score, height velocity, and general well-being that has persisted 2 years after the transplantation procedure. Autologous PBSCT associated with the infusion of the monoclonal antibody CAMPATH-1G appears to be a useful therapy for otherwise intractable forms of progressive systemic sclerosis.
Adolescent↗
Aortic valve regurgitation as the presenting sign of Takayasu arteritis.
UNLABELLED: Takayasu arteritis is a rare chronic vasculitis primarily involving the aorta and its main branches. We report an adolescent girl with Takayasu arteritis who presented with an isolated aortic valve regurgitation as part of a systemic inflammatory process. This patient was initially misdiagnosed as having rheumatic heart disease and the correct diagnosis was made only 1 year later. CONCLUSION: Takayasu arteritis should be considered among the diagnostic possibilities in patients who present with an unexplained systemic inflammatory syndrome and a cardiac murmur.
Adolescent↗
The extended oligoarticular subtype is the best predictor of methotrexate efficacy in juvenile idiopathic arthritis.
OBJECTIVE: To determine whether demographic, clinical, and laboratory variables measurable at baseline predict the clinical efficacy or major toxic effects of methotrexate (MTX) therapy in children with chronic arthritis. STUDY DESIGN: Patient eligibility criteria: (1) monitored in our unit between 1986 and 1996 with a diagnosis of chronic arthritis and (2) treatment with MTX as the sole second-line agent and for at least 6 months. Outcomes investigated: (1) short-term (6-month) clinical response, (2) complete disease control, (3) disease relapse after MTX discontinuation after complete disease control, (4) aminotransferase elevation, (5) gastrointestinal toxicity. Independent variables that showed significant results with univariate tests or were clinically relevant for each outcome underwent multiple logistic or Poisson regression analyses. RESULTS: Eighty patients were available for analysis. The disease onset subtype was systemic in 37 patients, polyarticular in 20 patients, and oligoarticular in 23 patients (all with polyarticular course: extended oligoarticular subtype). The extended oligoarticular subtype was the best predictor for both the short-term clinical response (odds ratio 6.80, P =.02) and, together with a better functional ability, the complete disease control (rate ratio 3.85, P =.03 and rate ratio 3.29, P =.006, respectively). Patients with this subtype of chronic arthritis tended to have earlier, and more frequently, a disease relapse after MTX discontinuation. Thrombocytosis was the only significant risk factor for liver biochemical abnormalities (rate ratio 2.94, P =.008), whereas no variable yielded significant results for gastrointestinal toxicity. CONCLUSION: Patients with extended oligoarticular chronic arthritis were more likely to benefit from MTX therapy and to have a relapse after treatment discontinuation, suggesting that MTX is distinctly more effective in this subset of chronic arthritis.
Adolescent↗
Responsiveness of outcome measures in juvenile chronic arthritis. Italian Pediatric Rheumatology Study Group.
OBJECTIVE: To examine the responsiveness of the disease activity measures more commonly used in juvenile chronic arthritis (JCA) clinical trials. METHODS: Data were obtained from an open-label, non-controlled, multicentre trial designed to investigate the efficacy of methotrexate (MTX) in children with JCA. Outcome measures, including physician and parent global assessments, functional ability measures, articular variables, and laboratory indicators of systemic inflammation, were assessed at baseline and after 6 months of MTX treatment in 132 patients. Responsiveness of endpoint variables was evaluated by assessing the effect size (ES) and the standardized response median (SRM). RESULTS: Physician and parent global assessments were the more responsive instruments, showing ES and SRM above 1.0. Erythrocyte sedimentation rate, C-reactive protein, functional status measures and articular variables showed intermediate responsiveness. Morning stiffness, haemoglobin and platelet count were the least responsive instruments. CONCLUSION: The results of our analysis indicate that subjective estimations of the disease activity, either by the physician or parents, are the most responsive instruments in the assessment of the therapeutic response in children with JCA. The responsiveness of outcome measures in JCA should be further investigated in prospective controlled studies.
Adolescent↗
Marked and sustained improvement 2 years after autologous stem cell transplantation in a girl with systemic sclerosis.
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Child, Preschool↗
Wegener's granulomatosis presenting with life-threatening pulmonary hemorrhage in a boy with type 1 diabetes.
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Child↗
Responsiveness of clinical measures in children with oligoarticular juvenile chronic arthritis.
OBJECTIVE: To compare the relative responsiveness of outcome measures in children with oligoarticular course juvenile chronic arthritis (JCA). METHODS: Twenty-six consecutive children with JCA and < or =4 joints involved were assessed at admission and after 3 months of followup. Outcome measures included physician and parent global assessments, functional ability as measured by the Childhood Health Assessment Questionnaire (CHAQ), articular variables, and laboratory indicators of systemic inflammation. Responsiveness was calculated with the standardized response median, the effect size, and the Guyatt method. RESULTS: The physician global assessment of disease activity, the active joint count, the global articular severity score, and the number and score of swollen joints proved consistently more responsive with either responsiveness measure used. The parent global assessment of the child's well being, the scores of joints with pain/tenderness and limited range of motion, and the number of joints with limited range of motion showed intermediate responsiveness. The CHAQ, morning stiffness, and laboratory indicators of systemic inflammation were the least responsive measures. CONCLUSION: The subjective estimation of disease activity by the physician and the articular variables were the more responsive outcome measures in children with oligoarticular JCA. The assessment of functional ability as measured by the CHAQ showed a poor sensitivity to clinical change in this subset of patients with JCA.
Adolescent↗
Mobilization and selection of peripheral blood hematopoietic progenitors in children with systemic sclerosis.
BACKGROUND AND OBJECTIVE: Autologous transplant of lymphocyte-depleted peripheral blood stem cells has been proposed for treatment of patients with severe autoimmune disease. However, until now, no data are available on the safety and feasibility of both stem cell collection and selection in pediatric patients with these disorders. We report on three children affected by systemic sclerosis with lung involvement, who received chemotherapy and granulocyte colony-stimulating factor (G-CSF) to mobilize autologous peripheral blood progenitors. DESIGN AND METHODS: The priming regimen consisted of cyclophosphamide (CY, 4 g/m(2)) and G-CSF (lenograstim, 10 microg/kg/day starting 2 days after cyclophosphamide administration until stem cell collection). Leukapheresis was performed when WBC and CD34+ cell count were at least 2 x 10(9)/L and 0.03 x 10(9)/L, respectively. In the first patient, positive selection of CD34+ cells was performed through the Ceprate SC stem cell concentrator (CellPro, Bothell, WA, USA). In the remaining 2 children, progenitor cells were also purged with negative selection of CD4+ and CD8+ lymphocytes performed by means of the Isolex 300i device (Baxter). RESULTS: All patients tolerated the priming regimen well and did not present any sign of autoimmune disease exacerbation. Collection was successful in all children and the number of CD34+ cells before selection ranged between 10.7 x 10(6) and 17.6 x 10(6)/kg of patient body weight. The selection of haematopoietic stem cells in the 3 patients resulted in at least 2. 6-log T-cell depletion of the cell content, with a recovery of the initial value of CD34+ cells comprised between 21 and 44%. After, a preparative regimen consisting of CY (200 mg/kg over 4 days) and Campath-1 G in vivo (10 mg/day for 2 consecutive days), patients were transplanted using cryopreserved lymphocyte-depleted progenitor cells. In all cases, a prompt hematopoietic engraftment was observed. INTERPRETATION AND CONCLUSIONS: Taken together these data suggest that mobilization, collection and selection of hematopoietic progenitors are safe and feasible in children with autoimmune disease.
Autoimmune Diseases↗
The Netherlands Mental Health Survey and Incidence Study (NEMESIS): objectives and design.
The article describes the objectives and design of a prospective study of the prevalence, incidence and course of psychiatric disorders in a representative sample of non-institutionalized Dutch adults. A total of 7146 men and women aged 18-64, contacted through a multistage sample of municipalities and households, were interviewed at home in 1996. The primary diagnostic instrument was the CIDI, which determines the lifetime occurrence of DSM-III-R disorders. The disorders included were: mood disorders, anxiety disorders, eating disorders, schizophrenia and other non-affective psychotic disorders, and dependence and abuse of psychoactive substances. Follow-up measurements in the same sample were scheduled at 12 and 36 months. The net response to the first measurement was 69.7%. Poststratification weightings were applied for gender, age, marital status and degree of urbanization. Limitations and advantages of the study design are discussed. Findings are reported elsewhere in this issue.
Adolescent↗
Prevalence of psychiatric disorder in the general population: results of The Netherlands Mental Health Survey and Incidence Study (NEMESIS).
This article reports the initial results of a prospective study on the prevalence of psychiatric disorders in the Dutch population aged 18-64. The objectives and the design of the study are described elsewhere in this issue. A total of 7076 people were interviewed in person in 1996. The presence of the following disorders was determined by means of the CIDI: mood disorders, anxiety disorders, eating disorders, schizophrenia and other non-affective psychoses, and substance use disorders. Psychiatric disorders were found to be quite common. Some 41.2% of the adult population under 65 had experienced at least one DSM-III-R disorder in their lifetime, among them 23.3% within the preceding year. No gender differences were found in overall morbidity. Depression, anxiety, and alcohol abuse and dependence were most prevalent, and there was a high degree of comorbidity between them. The prevalence rate encountered for schizophrenia was lower (0.4% lifetime) than generally presumed. A comparison with findings from other countries is made. Relevant determinants of psychiatric morbidity were analysed.
Adolescent↗
Radiologic progression in patients with juvenile chronic arthritis treated with methotrexate.
We investigated the rate of radiologic progression, as measured by carpal length, in 26 children with juvenile chronic arthritis who were treated with methotrexate. After 2 years of treatment, the carpal length was significantly more deteriorated in nonresponders in both the "better" wrist (P = .001) and the "worse" wrist (P = .005). These results show that methotrexate may have a "disease modifying" potential in juvenile chronic arthritis.
Adolescent↗
Performance of the preliminary definition of improvement in juvenile chronic arthritis patients treated with methotrexate. Italian Pediatric Rheumatology Study Group.
OBJECTIVE: To investigate the performance of the core set of outcome measures and the preliminary definition of improvement (PDI) in the assessment of response to methotrexate (MTX) treatment in children with juvenile chronic arthritis (JCA). METHODS: Data were obtained from an open label, non-controlled trial designed to investigate the efficacy of MTX in children with JCA. All patients had the core set of variables assessed at baseline and after six months of treatment. Variables in the core set are: (1) physician global assessment of disease activity; (2) parent or patient (if appropriate in age) global assessment of overall well being; (3) functional ability; (4) number of joints with active arthritis; (5) number of joints with limited range of motion; (6) erythrocyte sedimentation rate. The PDI specifies that to be classified as improved, a patient must show at least 30% improvement from baseline in three of any six variables in the core set, with no more than one of the remaining variables worsening by more than 30%. RESULTS: A total of 111 JCA patients were included in the study. According to the PDI, after six months of MTX treatment 73 patients (66%) were classified as improved and 38 (34%) as not improved. Among the core set variables, parent assessment detected the highest percentage of patients improved (72%) and functional assessment the lowest (37%). CONCLUSION: The PDI identifies about two thirds of patients with JCA treated with low dose MTX as improved. This proportion is similar to that expected to improve based upon a previous controlled study of low dose, oral MTX and provides preliminary evidence of the definition's validity.
Adolescent↗
Methotrexate therapy in refractory pediatric onset systemic lupus erythematosus.
OBJECTIVE: To evaluate the efficacy, safety, and corticosteroid sparing potential of methotrexate (MTX) in patients with pediatric onset systemic lupus erythematosus (SLE). METHODS: The medical records of 11 patients with SLE with onset before age 16 years were reviewed. Details of clinical features, previous therapy, indications for MTX, efficacy, toxicity, and corticosteroid reduction during MTX therapy were recorded. RESULTS: At the start of MTX treatment, 7 patients had nephritis, 3 malar rash, 3 arthritis, 2 skin vasculitis, and 2 thrombocytopenia. All patients were given MTX (12.5-17.0 mg/m2/week) as the sole drug therapy along with prednisone. Although many patients showed initial improvement and/or were able to reduce the prednisone dose, after 7 to 23 months 8 patients had a flare of SLE requiring increased doses of prednisone, one patient had unchanged SLE activity, and 2 patients were permanently discontinued from MTX because of toxicity. Side effects were observed in 8 (73%) patients, but only 2 (18%) discontinued MTX due to toxicity. CONCLUSION: MTX given as the sole drug therapy along with prednisone did not show a major corticosteroid sparing potential in our patients with pediatric onset SLE.
Adolescent↗
[Psychiatric morbidity among adults in The Netherlands: the NEMESIS-Study. I. Objectives, design and methods. Netherlands Mental Health Survey and Incidence Study].
OBJECTIVE: To determine prevalence, incidence and course of psychiatric disorders in non-institutionalised Dutch adults. DESIGN: Prospective and cross-sectional. SETTING: Trimbos Institute, Utrecht, the Netherlands. METHOD: A multistage, stratified random sampling procedure was used to obtain a sample of 7076 adults (18-64 years). Respondents were interviewed throughout 1996 in their homes. The main diagnostic instrument was the 'Composite international diagnostic interview' (CIDI), designed to assess lifetime prevalence of mental disorders according to Diagnostic and statistical manual of mental disorders, 3rd revised edition (DSM-III-R). The diagnostic categories were: affective disorders, anxiety disorders, eating disorders, schizophrenia and other non-affective psychoses, and substance use disorders (dependence and abuse). The sample was weighted towards national census data on sex, age, marital status and urbanicity. RESULTS: The results of the first measurement (1996) will be described in the next article (1997:2353-60). The response rate was 64.2%. There were no indications that the psychiatric morbidity of non-respondents differed from respondents. The same respondents will be interviewed again after 12 (1997) and after 36 months (1999).
Adolescent↗
[Psychiatric morbidity among adults in The Netherlands: the NEMESIS-Study. II. Prevalence of psychiatric disorders. Netherlands Mental Health Survey and Incidence Study].
OBJECTIVE: To determine the prevalence of psychiatric disorders in non-institutionalised Dutch adults. DESIGN: Cross-sectional. SETTING: Trimbos Institute, Utrecht, the Netherlands. METHODS: A representative sample of 7076 adults (18-64 years) in the Netherlands' population were interviewed in 1996 to determine the prevalence of mental disorders ever, in the previous 12 months and in the previous month. Objectives and study design are described in the previous article (1997: 2448-52). The 'Composite international diagnostic interview' (CIDI) was used to assess the following mental disorders according to Diagnostic and statistical manual of mental disorders, 3rd revised edition (DSM-III-R): affective disorders, anxiety disorders, eating disorders, schizophrenia and other non-affective psychoses, substance dependence and substance abuse. RESULTS: Mental disorders were common in the general population: the prevalence 'ever' of all disorders was 41.2%, the 12-month prevalence 23.5%, without sex differences. Depression, anxiety disorders and alcohol abuse and dependence showed high prevalence and comorbidity. The prevalence 'ever' of schizophrenia and other non-affective psychoses was low (0.4%).
Adolescent↗
Preliminary definition of improvement in juvenile arthritis.
OBJECTIVE: To identify a core set of outcome variables for the assessment of children with juvenile arthritis (JA), to use the core set to develop a definition of improvement to determine whether individual patients demonstrate clinically important improvement, and to promote this definition as a single efficacy measure in JA clinical trials. METHODS: A core set of outcome variables was established using a combination of statistical and consensus formation techniques. Variables in the core set consisted of 1) physician global assessment of disease activity; 2) parent/patient assessment of overall well-being; 3) functional ability; 4) number of joints with active arthritis; 5) number of joints with limited range of motion; and 6) erythrocyte sedimentation rate. To establish a definition of improvement using this core set, 21 pediatric rheumatologists from 14 countries met, and, using consensus formation techniques, scored each of 72 patient profiles as improved or not improved. Using the physicians' consensus as the gold standard, the chi-square, sensitivity, and specificity were calculated for each of 240 possible definitions of improvement. Definitions with sensitivity or specificity of <80% were eliminated. The ability of the remaining definitions to discriminate between the effects of active agent and those of placebo, using actual trial data, was then observed. Each definition was also ranked for face validity, and the sum of the ranks was then multiplied by the kappa statistic. RESULTS: The definition of improvement with the highest final score was as follows: at least 30% improvement from baseline in 3 of any 6 variables in the core set, with no more than 1 of the remaining variables worsening by >30%. The second highest scoring definition was closely related to the first; the third highest was similar to the Paulus criteria used in adult rheumatoid arthritis trials, except with different variables. This indicates convergent validity of the process used. CONCLUSION: We propose a definition of improvement for JA. Use of a uniform definition will help standardize the conduct and reporting of clinical trials, and should help practitioners decide if a child with JA has responded adequately to therapy. We are in the process of prospectively validating this definition and several others that scored highly.
Arthritis, Rheumatoid↗
Antiphospholipid antibody syndrome in pediatric patients.
The antiphospholipid antibody syndrome is characterized by the association between recurrent arterial or venous thrombosis and the presence of circulating antiphospholipid antibodies. Antiphospholipid antibody-related thrombosis seems to constitute a significant proportion of childhood thromboses. About one third of children suffering a thrombotic event have circulating antiphospholipid antibodies, and more than two thirds of children with idiopathic cerebral ischemia meet the criteria for the diagnosis of antiphospholipid antibody syndrome. Because the other risk factors for thrombosis commonly found in adults have no impact on the pediatric patient, the risk for thrombosis and thrombotic recurrences and the optimal anticoagulation therapy may differ from adults.
Adolescent↗