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ABSTRACT: OBJECTIVES: To determine the two-year outcome of patients with later-onset polyarticular rheumatoid factor (RF) negative (-) juvenile idiopathic arthritis (JIA), and predictors of outcome. METHODS: All patients ages 10 to16 years diagnosed and followed in the Rheumatology Clinic at SickKids Hospital with the diagnosis of polyarticular RF- JIA were eligible for study. A retrospective chart analysis was performed and number of active joints, medications, laboratory information and childhood health assessment questionnaire scores were recorded at diagnosis, and 6, 12, and 24 months following diagnosis. RESULTS: As early as 6 months after diagnosis the mean number of active joints decreased from 16 to < 10, with 50% of the patients having < 5 active joints. The predominant joints affected were the wrist, knee, and small joints of the hand. The only predictor of active joint count at the 2-year follow-up was initial presenting active joint count as classified as mild, moderate, or severe. Sex, age, and laboratory results at presentation did not show any correlation with active joint count at 2 years. Majority of patients were treated with non-steroidal anti-inflammatory drugs (98%) and at least one disease-modifying anti-rheumatic drug (56%). CONCLUSIONS: The two-year outcome of patients with late-onset RF- polyarticular JIA was very good with the majority of patients having minimally active disease at last follow-up. Presence of significant polyarthritis at presentation was the only feature associated with long-term joint activity. Sex and lab results did not show any correlation with active joint in this cohort of RF- JIA patients.
Clinical and experimental rheumatology 04/2013; · 2.15 Impact Factor
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ABSTRACT: OBJECTIVE: (1) To describe the clinical course and response to treatment; and (2) to evaluate and compare damage accrual of distinct phenotypic subgroups of patients with clinically important psychiatric illness of pediatric systemic lupus erythematosus (pSLE). METHODS: A single-center cohort study of patients with pSLE followed at a pediatric lupus clinic from 1985 to July 2009. Clinical course and response to treatment were studied. Remission was defined by absence of psychiatric/cognitive symptoms while receiving minimal doses of prednisone. Disease activity and damage were measured using SLE Disease Activity Index and SLE Damage Index. RESULTS: Fifty-three children were included: 40 with psychosis and cognitive dysfunction (PSYC group) and 13 with isolated cognitive dysfunction (COG group). All received immunosuppressive treatment. Eighteen of 32 treated with azathioprine required a change to cyclophosphamide for poor response but none on cyclophosphamide required a change. The median times to remission were 72 weeks (PSYC) and 70 weeks (COG). Eight patients (7 PSYC, 1 COG) experienced flare following response/remission. New damage was noted in 50% of children at a median of 11 months: 57% of PSYC group, 31% of COG group. Persistent cognitive dysfunction was seen in 16% of PSYC patients and 15% of COG patients. CONCLUSION: Most patients responded to immunosuppressive treatment, although median time to remission was > 1 year. Roughly half the patients acquired a new damage item, most of which did not interfere with functional abilities. Fewer than 20% of patients developed neuropsychiatric damage. Both phenotypes of psychiatric pSLE responded equally well to current treatment.
The Journal of Rheumatology 03/2013; · 3.69 Impact Factor
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ABSTRACT: OBJECTIVES: Physicians often assess the effectiveness of treatments on a small number of patients. Multiple-baseline designs (MBDs), based on the Wampold-Worsham (WW) method of randomization and applied to four subjects, have relatively low power. Our objective was to propose another approach with greater power that does not suffer from the time requirements of the WW method applied to a greater number of subjects. STUDY DESIGN AND SETTING: The power of a design that involves the combination of two four-subject MBDs was estimated using computer simulation and compared with the four- and eight-subject designs. The effect of a delayed linear response to treatment on the power of the test was also investigated. RESULTS: Power was found to be adequate (>80%) for a standardized mean difference (SMD) greater than 0.8. The effect size associated with 80% power from combined tests was smaller than that of the single four-subject MBD (SMD=1.3) and comparable with the eight-subject MBD (SMD=0.6). A delayed linear response to the treatment resulted in important reductions in power (20-35%). CONCLUSIONS: By combining two four-subject MBD tests, an investigator can detect better effect sizes (SMD=0.8) and be able to complete a comparatively timelier and feasible study.
Journal of clinical epidemiology 03/2013; · 2.96 Impact Factor
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ABSTRACT: PURPOSE: To determine the influence of ethnicity and sociodemographic factors on disease characteristics of the Canadian Pediatric Lupus population. METHODS: Childhood-onset SLE (cSLE) patients at four pediatric centers in Halifax, Montreal, Toronto and Vancouver were consecutively recruited. Sociodemographics and disease data were collected. Patients were categorized by their primary self-selected ethnicity, and exploratory cluster analyses were examined for disease expression by ethnicity. RESULTS: We enrolled 213 cSLE patients, and ethnicity data were available for 206 patients: White (31%), Asian (30%), South Asian (15%), Black (10%), Latino/Hispanic (4%), Aboriginal (4%) and Arab/Middle Eastern (3%). The frequency of clinical classification criteria (malar rash, arthritis, serositis and renal disease) and autoantibodies significantly differed among ethnicities. Medications were prescribed equally across ethnicities: 76% were taking prednisone, 86% anti-malarials, and 56% required additional immunosuppressants. Cluster analysis partitioned three main groups - mild (N = 50), moderate (N = 82) and severe (N = 68) disease clusters. Only 20% of White patients were in the severe cluster compared to 51% of Asian and 41% of Black patients (p=0.03). However, disease activity indices and damage scores were similar across ethnicities. CONCLUSION: Canadian cSLE patients reflect our multi-ethnic population, with differences in disease manifestations, autoantibody profiles and severity of disease expression by ethnicity. © 2012 by the American College of Rheumatology.
Arthritis care & research. 06/2012;
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ABSTRACT: (1) To identify the average lumbar spine (LS) bone mineral density (BMD) trajectory in paediatric systemic lupus erythematosus (pSLE) patients, and (2) to identify predictors of BMD trajectory.
68 consecutive newly diagnosed pSLE patients prospectively followed in our lupus cohort with three annual dual energy x-ray absorptiometry (DEXA) examinations were studied. Low LS BMD was defined as z-score ≤-2.0. Baseline and longitudinal clinical features including disease activity, treatment and bone physiology markers were collected. Hierarchical linear modelling was used to model trajectory of LS BMD and identify predictors.
Women constituted 84% of the cohort and median age at diagnosis was 13.1 years. The mean LS BMD z-scores decreased over time (-0.42 at first, -1.02 at second and -1.11 at third DEXA). Initially 9% of patients had a low BMD, which increased to 19% by 3 years after diagnosis. 35% of patients deteriorated in BMD category from the first to third DEXA. LS BMD (adjusted by height-for-age z-score) followed a general deteriorating trajectory of -0.06 z-score/year from diagnosis. Increased rate of deterioration of BMD trajectory was predicted by pubertal status at diagnosis, increased interval cumulative steroid exposure and decreased weight z-scores.
The LS BMD of pSLE patients followed a general deteriorating trend over time and could be predicted by a combination of pubertal status at diagnosis, interval cumulative doses of steroids and weight z-scores. Interval cumulative steroid dose represents an important target that clinicians may modify to ameliorate deteriorating BMD trajectory over time.
Annals of the rheumatic diseases 03/2012; 71(10):1686-91. · 8.11 Impact Factor
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Ophthalmology 12/2011; 118(12):2524; author reply 2524-5. · 5.45 Impact Factor
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ABSTRACT: The objectives of this study were to (1) determine the prevalence of low bone mineral density (BMD) in a large prospective cohort of newly diagnosed patients with paediatric systemic lupus erythematosus (pSLE) and (2) identify risk factors associated with low BMD.
Single-centre cohort study of 80 children and adolescents who underwent a dual-energy x-ray absorptiometry within 3 months of diagnosis. Low lumbar spine (LS) BMD was defined as z score ≤ -2.0. BMD was correlated with baseline demographic, clinical and laboratory markers of disease activity and biochemical markers of bone health. Risk factors of BMD were evaluated with univariable and multivariable linear and logistic regression analyses.
Low BMD at any site was found in 15% of newly diagnosed pSLE patients. LS BMD was associated with body mass index (BMI) z score and corrected calcium (r(2)=0.31, p<0.0001). Hip BMD was associated with BMI z score and intact parathyroid hormone (iPTH) (r(2)=0.26, p=0.002). Higher BMI z score was protective against low BMD at any site (OR 0.35).
One in six newly diagnosed pSLE patients had low BMD (at any site). Low BMI z score, low calcium and high iPTH identified children at risk for low BMD at diagnosis of pSLE.
Annals of the rheumatic diseases 09/2011; 70(11):1991-4. · 8.11 Impact Factor
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ABSTRACT: To assess traditional and non-traditional cardiovascular risk factors and to determine the prevalence and correlates of early vascular markers of atherosclerosis in paediatric systemic lupus erythematosus (pSLE).
Fifty-four adolescents with pSLE had cardiovascular risk factor assessment, disease activity and vascular testing including carotid intima-media thickness (CIMT), flow-mediated dilatation (FMD), arterial stiffness measures, and myocardial perfusion studies.
The traditional risk factors of hypertension, elevated triglycerides, apolipoprotein B, haemoglobin A1c and insulin levels and non-traditional risk factors of elevated homocysteine and fibrinogen were present (all p<0.001). Some arterial stiffness measures, central pulse wave velocity and characteristic impedance were elevated (p<0.001), but CIMT, FMD and myocardial perfusion were normal. Cumulative prednisone dose correlated with total cholesterol (r=0.5790, p<0.001) and elevated LDL-C (r=0.4488, p=0.0012). Hydroxychloroquine treatment correlated negatively with total cholesterol (r=-0.4867, p=0.0002), LDL-C (r=-0.4805, p=0.0002) and apolipoprotein B (r=-0.4443, p=0.0011). In multivariate analysis LDL-C correlated with cumulative prednisone dose and negatively with hydroxychloroquine treatment (R2=0.40, p<0.001).
An increased burden of traditional and non-traditional risk factors and early evidence of insulin resistance and increased central arterial stiffness were present in paediatric SLE. Disease-specific and therapy-related factors are likely modifying these cardiovascular risk profiles warranting prospective longitudinal studies.
Clinical and experimental rheumatology 05/2011; 29(3):575-81. · 2.15 Impact Factor
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ABSTRACT: We prospectively examined the prevalence and outcome of untreated fetal atrioventricular (AV) prolongation in the presence of maternal anti-Ro antibodies.
It has been suggested that antibody-mediated congenital complete atrioventricular block (CAVB) may be preventable if detected and treated early when low-grade block is present. With this rationale in mind, dexamethasone has been advocated by others to treat prolonged fetal AV conduction >2 z-scores, consistent with first-degree heart block.
Between July 2003 and June 2009, 165 fetuses of 142 anti-Ro/La antibody-positive women were referred to our center for serial echocardiography. Our protocol included weekly evaluation of the fetal AV conduction between 19 (range 17 to 23) and 24 (range 23 to 35) gestational weeks. AV times were compared with institutional reference data and with post-natal electrocardiograms.
Of 150 fetuses with persistently normal AV conduction throughout the observation period, a diagnosis of CAVB was subsequently made in 1 at 28 weeks, after the serial evaluation had ended. Of 15 untreated fetuses either with AV prolongation between 2 and 6 z-scores or with type 1 second-degree block, progressive heart block developed in none of them. Three of these 15 fetuses (20%) had a neonatal diagnosis of first-degree block that spontaneously resolved (n = 2) or has not progressed (n = 1) on follow-up examinations. No other cardiac complications were detected.
Fetal AV prolongation did not predict progressive heart block to birth. Our findings question the rationale of a management strategy that relies on the early identification and treatment of fetal AV prolongation to prevent CAVB.
Journal of the American College of Cardiology 03/2011; 57(13):1487-92. · 14.16 Impact Factor
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ABSTRACT: Systemic lupus erythematosus (SLE) is a chronic, multisystem autoimmune disease with a highly variable clinical course. Pediatric-onset SLE (pSLE) represents 10-20% of all SLE cases, and is associated with higher disease severity, including more-rapid damage accrual, than adult-onset SLE. As in adults, pSLE disease expression varies according to ethnicity, with a milder disease course in white patients. The majority of pSLE patients will have developed damage within 5-10 years of disease onset, most frequently involving the musculoskeletal, ocular, renal and neuropsychiatric systems. Owing to improvements in disease management and recognition over the past 20-30 years, patients now live longer, but as a result have increased disease damage. Premature atherosclerosis and osteoporosis have become increasingly prevalent morbidities in pSLE patients. Early atherosclerosis leads to a considerable rise in cardiovascular and cerebrovascular events, and failure to develop adequate peak bone mass during adolescence-a crucial period of bone accrual-is likely to lead to early osteoporosis and fractures. Patients with pSLE have an incurable, potentially devastating disease that occurs during a vulnerable period of psychosocial development, leading to specific and unique psychosocial stressors. Additional large, long-term follow-up studies in pSLE are needed to better understand the disease prognosis and to facilitate development of tailored treatments.
Nature Reviews Rheumatology 09/2010; 6(9):538-46. · 8.39 Impact Factor
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Nicolino Ruperto,
Daniel J Lovell,
Ruben Cuttica,
Patricia Woo,
Silvia Meiorin,
Carine Wouters, Earl D Silverman,
Zsolt Balogh,
Michael Henrickson,
Joyce Davidson, [......],
Lisa Imundo,
Gabriele Simonini,
Joachim Oppermann,
Stephen Xu,
Yaung-Kaung Shen,
Sudha Visvanathan,
Adedigbo Fasanmade,
Alan Mendelsohn,
Alberto Martini,
Edward H Giannini
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ABSTRACT: To assess the long-term efficacy and safety of infliximab plus methotrexate in juvenile rheumatoid arthritis (JRA).
Patients eligible for the open-label extension (OLE, weeks 52-204) received infliximab 3-6 mg/kg every 8 weeks plus methotrexate.
Of the 78/122 (64%) children entering the OLE, 42 discontinued infliximab, most commonly due to consent withdrawal (11 patients), lack of efficacy (eight patients) or patient/physician/sponsor requirement (eight patients). Infliximab (mean dose 4.4 mg/kg per infusion) was generally well tolerated. Infusion reactions occurred in 32% (25/78) of patients, with a higher incidence in patients positive for antibodies to infliximab (58%, 15/26). At week 204, the proportions of patients achieving ACR-Pedi-30/50/70/90 response criteria and inactive disease status were 44%, 40%, 33%, 24% and 13%, respectively.
In the limited population of JRA patients remaining in the study at 4 years, infliximab was safe and effective but associated with a high patient discontinuation rate.
Annals of the rheumatic diseases 04/2010; 69(4):718-22. · 8.11 Impact Factor
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Shikha Mittoo,
Allan C Gelber,
Carol A Hitchon, Earl D Silverman,
Janet E Pope,
Paul R Fortin,
Christian Pineau,
C Douglas Smith,
Hector Arbillaga,
Dafna D Gladman,
Murray B Urowitz,
Michel Zummer,
Ann E Clarke,
Sasha Bernatsky,
Marie Hudson,
Lori B Tucker,
Ross E Petty,
Christine A Peschken
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ABSTRACT: Pleuritis is a common manifestation and independent predictor of mortality in systemic lupus erythematosus (SLE). We examined the prevalence of pleuritis and factors associated with pleuritis in a multicenter Canadian SLE cohort.
We studied consecutive adults satisfying the American College of Rheumatology (ACR) classification criteria for SLE who had a completed Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI) score, at least 1 evaluable extractable nuclear antigen assay, and either a SLE Disease Activity Index (SLEDAI) or a SLE Activity Measure score. Pleuritis was defined as having pleuritis by satisfying the ACR criteria or the SLEDAI. Factors related to pleuritis were examined using univariate and multivariate logistic regression.
In our cohort of 876 patients, 91% were women, 65% Caucasian, mean age (+/- SD) was 46.8 +/- 13.5 years, and disease duration at study entry was 12.1 +/- 9.9 years; the prevalence of pleuritis was 34% (n = 296). Notably, greater disease duration (p = 0.002), higher SDI score (p <or= 0.0001), age at SLE diagnosis (p = 0.009), and anti-Sm (p = 0.002) and anti-RNP (p = 0.002) seropositivity were significantly associated with pleuritis. In multivariate analysis with adjustment for disease duration, age at diagnosis, and SDI score, concomitant seropositivity for RNP and Sm were related to a nearly 2-fold greater prevalence of pleuritis (OR 1.98, 95% CI 1.31-2.82).
Pleuritis occurred in one-third of this Canadian cohort. Concomitant Sm and RNP seropositivity, greater cumulative damage, longer disease duration, and younger age at SLE disease onset were related to a higher rate of SLE pleural disease.
The Journal of Rheumatology 04/2010; 37(4):747-53. · 3.69 Impact Factor
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ABSTRACT: To perform a systematic review and meta-analysis to examine whether rheumatic disease is associated with an increased carotid intima-media thickness (CIMT; increasingly used as a surrogate marker for atherosclerosis) when compared with healthy control subjects.
A prespecified search strategy was used to identify relevant studies in the MEDLINE and EMBASE databases (January 1, 1986 to December 31, 2008). Methodological quality was assessed using the Newcastle-Ottawa score for observational studies. A total of 68 controlled comparisons from 60 different studies were reviewed: 25 (37%) on rheumatoid arthritis, 24 (35%) on systemic lupus erythematosus, 6 (9%) on systemic sclerosis, and 13 (19%) on other rheumatic diseases. Random-effects meta-regression analysis was performed. The estimated summary effect size between control and study subject CIMT measurement comparisons, with preexisting cardiovascular disease excluded, was 0.64 (95% CI, 0.46 to 0.82). This represented an overall absolute mean difference of 0.06 mm (95% CI, 0.05 to 0.06 mm). Preexisting cardiovascular disease, rheumatic disease type, and disease duration contributed to heterogeneity.
Accelerated atherosclerosis is a common complication of autoimmune rheumatic diseases, with early changes seen even in pediatric patients. CIMT was significantly increased in rheumatic disease populations. Future studies need to use a standardized protocol to ensure clinically meaningful results when measuring CIMT as a surrogate for premature atherosclerosis.
Arteriosclerosis Thrombosis and Vascular Biology 02/2010; 30(5):1014-26. · 6.37 Impact Factor
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ABSTRACT: Prevalence and severity of systemic lupus erythematosus (SLE) in adults is suggested to be distinctly different between ethnic groups. The impact of ethnicity is not as well delineated in pediatric SLE (pSLE). We compared prevalence and extent of major organ involvement, disease activity, and damage in pSLE between different ethnic groups.
Ethnic demographic profiles of an inception cohort of 265 patients with pSLE followed at Sick Kids Hospital in Toronto were determined and compared to the Metropolitan Toronto at-risk population. Patients were categorized into ethnic subsets based on self-designated ethnic origins. Disease characteristics including major organ involvement, disease activity, and damage measures were longitudinally determined and compared among ethnic groups.
Ethnicity data were available on 259/265 pSLE patients (99.6%); the majority were non-Caucasian (60%) compared to the Metropolitan Toronto at-risk population (40%) (p < 0.0001). Non-Caucasian patients were younger at diagnosis than Caucasian patients, Black patients being the youngest at diagnosis (12.6 vs 14.6 yrs; p = 0.007). Renal disease was significantly more common in non-Caucasian than in Caucasian pSLE patients (62% vs 45%; p = 0.01). There was a trend toward increased prevalence of central nervous system disease in Black patients compared to Asian patients (p = 0.108). There was no difference in gender ratio, SLE Disease Activity Index, or damage scores between ethnic groups.
Non-Caucasian ethnicity is associated with increased pSLE disease prevalence. Non-Caucasian pSLE patients were significantly younger and more likely to have nephritis. However, disease activity and damage were strongly associated with major organ disease independent of the patient's ethnicity.
The Journal of Rheumatology 11/2009; 36(11):2539-46. · 3.69 Impact Factor
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Claas H Hinze,
Michiko Suzuki,
Marisa Klein-Gitelman,
Murray H Passo,
Judyann Olson,
Nora G Singer,
Kathleen A Haines,
Karen Onel,
Kathleen O'Neil, Earl D Silverman,
Lori Tucker,
Jun Ying,
Prasad Devarajan,
Hermine I Brunner
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ABSTRACT: To determine whether neutrophil gelatinase-associated lipocalin (NGAL) can predict worsening of global and renal disease activity in childhood-onset systemic lupus erythematosus (SLE).
One hundred eleven patients with childhood-onset SLE were enrolled in a longitudinal, prospective study with quarterly study visits and had at least 3 study visits. At each visit, global disease activity was measured using 3 external standards: the numerically converted British Isles Lupus Assessment Group (BILAG) index, the SLE Disease Activity Index 2000 update score, and the physician's assessment of global disease activity. Renal and extrarenal disease activity were measured by the respective domain scores. The disease course over time was categorized at the most recent visit (persistently active, persistently inactive, improved, or worsening). Plasma and urinary NGAL levels were measured by enzyme-linked immunosorbent assay, and urinary NGAL levels were standardized to the urinary creatinine concentration. The longitudinal changes in NGAL levels were compared with the changes in SLE disease activity using mixed-effect models.
Significant increases in standardized urinary NGAL levels of up to 104% were detected up to 3 months before worsening of lupus nephritis (as measured by all 3 external standards). Plasma NGAL levels increased significantly by as much as 26% up to 3 months before worsening of global SLE disease activity as measured by all 3 external standards. Plasma NGAL levels increased significantly by 26% as early as 3 months prior to worsening of lupus nephritis as measured by the BILAG renal score.
Serial measurement of urinary and plasma NGAL levels may be valuable in predicting impending worsening of global and renal childhood-onset SLE disease activity.
Arthritis & Rheumatism 09/2009; 60(9):2772-81. · 7.87 Impact Factor
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Yonatan Aviel Butbul,
Pascal N Tyrrell,
Rayfel Schneider,
Sandeep Dhillon,
Brian M Feldman,
Ronald M Laxer,
Rotraud K Saurenmann,
Lynn Spiegel,
Bonnie Cameron,
Shirley M Tse, Earl D Silverman
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ABSTRACT: To compare the clinical features and outcome between patients with juvenile psoriatic arthritis (JPsA) and non-JPsA juvenile idiopathic arthritis (JIA).
Fifty-three children with JPsA, 32 with < 5 joints in the first 6 months of disease (oligo-JPsA) and 21 (> or = 5 joints) polyarticular-onset (poly-JPsA) were compared to 53 patients with JIA who were matched by sex, age, date of diagnosis, and articular onset pattern.
There was no difference in the percentage of patients between the oligoarticular groups who developed extended oligoarthritis or in the percentage of patients who were positive for antinuclear antibodies. The only differences were that 25% of patients with oligo-JPsA had dactylitis compared to 0% of patients with oligo-JIA (p < 0.01) and 50% had nail pitting as compared to 18.7% (p < 0.05). In polyarticular patients the percentages with dactylitis were similar (19% vs 38%; p = 0.25). The frequency of uveitis was identical in the oligoarticular patients but a higher rate was seen in poly-JPsA compared to poly-JIA (23.8% vs 0%; p = 0.02), while contractures were more frequent in poly-JIA compared to poly-JPsA during the course of the illness (47.6% vs 14.3%; p = 0.03) but not at last followup (14.3% vs 4.7%; p = 0.6). At last followup the mean Childhood Health Assessment Questionnaire scores were similar in both the polyarticular and oligoarticular groups.
There were only a few differences between patients with JPsA and JIA regarding disease onset, disease course, and outcome. We suggest that large, longterm prospective studies are required to accurately determine whether subdividing JIA according to psoriasis is worthwhile.
The Journal of Rheumatology 07/2009; 36(9):2033-41. · 3.69 Impact Factor
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Circulation 06/2009; 119(20):e539; author reply e541-2. · 14.74 Impact Factor
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Nicolino Ruperto,
Daniel J Lovell,
Ruben Cuttica,
Patricia Woo,
Silvia Meiorin,
Carine Wouters, Earl D Silverman,
Zsolt Balogh,
Michael Henrickson,
Joyce Davidson,
Ivan Foeldvari,
Lisa Imundo,
Gabriele Simonini,
Joachim Oppermann,
Yaung-Kaung Shen,
Sudha Visvanathan,
Adedigbo Fasanmade,
Alan Mendelsohn,
Alberto Martini,
Edward H Giannini
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ABSTRACT: OBJECTIVE: Assess long-term efficacy and safety of infliximab plus methotrexate (MTX) in juvenile rheumatoid arthritis (JRA). METHODS: Patients eligible for the open-label extension (OLE, weeks 52-204) received infliximab 3-6 mg/kg q8wks plus MTX. RESULTS: Of the 78/122 (64%) children entering the OLE, 42 discontinued infliximab, most commonly due to consent withdrawal (11 patients), lack of efficacy (8 patients) or patient/physician/sponsor requirement (8 patients). Infliximab (mean dose=4.4 mg/kg/infusion) was generally well tolerated. Infusion reactions occurred in 32% (25/78) of patients, with a higher incidence in patients positive for antibodies to infliximab (58%, 15/26). At week 204, the proportions of patients achieving ACR-Pedi-30/50/70/90 response criteria and inactive disease status were 44%, 40%, 33%, 24%, and 13%, respectively. CONCLUSIONS: In the limited population of JRA patients remaining in the study through 4 years, infliximab was safe and effective but associated with a high patient discontinuation rate.
Annals of the rheumatic diseases 05/2009; · 8.11 Impact Factor
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ABSTRACT: Our goal was to determine long-term efficacy and safety of B-cell-depletion therapy for children with autoimmune thrombocytopenia and autoimmune hemolytic anemia in pediatric systemic lupus erythematosus.
A retrospective, single-center cohort study was conducted including all patients with pediatric systemic lupus erythematosus who were diagnosed with autoimmune thrombocytopenia and/or autoimmune hemolytic anemia and treated with rituximab. Treatment efficacy and safety parameters were monitored and recorded.
Nine patients with pediatric systemic lupus erythematosus were included in the study: 5 had autoimmune thrombocytopenia, 3 had autoimmune hemolytic anemia, and 1 had both. There were 5 female and 4 male patients; median age at diagnosis of pediatric systemic lupus erythematosus was 14 years (range: 8-16 years); and median pediatric systemic lupus erythematosus disease duration to time of rituximab treatment was 6 months (range: 2-30 months). Complete response was achieved in all 6 children with autoimmune thrombocytopenia (median time to complete response: 2 weeks [range: 1-12 weeks]). Two patients' conditions flared at 48 and 68 weeks, respectively, and were re-treated. The remaining 4 patients continued to be in remission at 24, 32, 36, and 88 weeks, respectively. All 4 children with autoimmune hemolytic anemia achieved complete response at a median time of 4 weeks (range: 4-32 weeks). All patients remained in complete response at 24, 44, 84, and 100 weeks of follow-up. Complete B-cell depletion was seen in all children after rituximab treatment. No serious infections occurred, but 1 patient had an infusion reaction.
Preliminary evidence suggests that B-cell-depletion therapy with rituximab is an efficacious and safe treatment for autoimmune thrombocytopenia and autoimmune hemolytic anemia in pediatric systemic lupus erythematosus. Despite the prolonged effect on B-cell numbers and function, no serious infections were observed.
PEDIATRICS 01/2009; 123(1):e159-63. · 4.47 Impact Factor
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Tadej Avcin,
Rolando Cimaz, Earl D Silverman,
Ricard Cervera,
Marco Gattorno,
Stella Garay,
Yackov Berkun,
Flavio R Sztajnbok,
Clovis A Silva,
Lucia M Campos,
Claudia Saad-Magalhaes,
Donato Rigante,
Angelo Ravelli,
Alberto Martini,
Blaz Rozman,
Pier Luigi Meroni
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ABSTRACT: The purpose of this study was to obtain data on the association of antiphospholipid antibodies with clinical manifestations in childhood and to enable future studies to determine the impact of treatment and long-term outcome of pediatric antiphospholipid syndrome.
A European registry extended internationally of pediatric patients with antiphospholipid syndrome was established as a collaborative project of the European Antiphospholipid Antibodies Forum and Lupus Working Group of the Pediatric Rheumatology European Society. To be eligible for enrollment the patient must meet the preliminary criteria for the classification of pediatric antiphospholipid syndrome and the onset of antiphospholipid syndrome must have occurred before the patient's 18th birthday.
As of December 1, 2007, there were 121 confirmed antiphospholipid syndrome cases registered from 14 countries. Fifty-six patients were male, and 65 were female, with a mean age at the onset of antiphospholipid syndrome of 10.7 years. Sixty (49.5%) patients had underlying autoimmune disease. Venous thrombosis occurred in 72 (60%), arterial thrombosis in 39 (32%), small-vessel thrombosis in 7 (6%), and mixed arterial and venous thrombosis in 3 (2%). Associated nonthrombotic clinical manifestations included hematologic manifestations (38%), skin disorders (18%), and nonthrombotic neurologic manifestations (16%). Laboratory investigations revealed positive anticardiolipin antibodies in 81% of the patients, anti-beta(2)-glycoprotein I antibodies in 67%, and lupus anticoagulant in 72%. Comparisons between different subgroups revealed that patients with primary antiphospholipid syndrome were younger and had a higher frequency of arterial thrombotic events, whereas patients with antiphospholipid syndrome associated with underlying autoimmune disease were older and had a higher frequency of venous thrombotic events associated with hematologic and skin manifestations.
Clinical and laboratory characterization of patients with pediatric antiphospholipid syndrome implies some important differences between antiphospholipid syndrome in pediatric and adult populations. Comparisons between children with primary antiphospholipid syndrome and antiphospholipid syndrome associated with autoimmune disease have revealed certain differences that suggest 2 distinct subgroups.
PEDIATRICS 12/2008; 122(5):e1100-7. · 4.47 Impact Factor
