Earl D Silverman

SickKids, Toronto, Ontario, Canada

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Publications (320)1448.34 Total impact

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    Su B · Capecchi M · Lung K · Manlhiot C · Yan YQ · Liu L · Cui R · Jaeggi ET · Silverman ED · Hamilton EM
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    Tsang W · Silverman E · Cui R · Su B · Wu X · Hamilton R
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    Su B · Capecchi M · Lung K · Manlhiot C · Yan YQ · Liu L · Cui R · Jaeggi ET · Silverman ED · Hamilton EM
  • L.S.H. Lim · E. Pullenayegum · L. Lim · D.D. Gladman · B.M. Feldman · E.D. Silverman
    Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):92.1-92. DOI:10.1136/annrheumdis-2015-eular.3512 · 10.38 Impact Factor
  • Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):421.1-421. DOI:10.1136/annrheumdis-2015-eular.4052 · 10.38 Impact Factor
  • Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):98.1-98. DOI:10.1136/annrheumdis-2015-eular.5017 · 10.38 Impact Factor
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    ABSTRACT: To describe probabilities and characteristics of disease flares in children with juvenile idiopathic arthritis (JIA) and to identify clinical features associated with an increased risk of flare. We studied children in the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) prospective inception cohort. A flare was defined as a recurrence of disease manifestations after attaining inactive disease and was called significant if it required intensification of treatment. Probability of first flare was calculated with Kaplan-Meier methods, and associated features were identified using Cox regression. 1146 children were followed up a median of 24 months after attaining inactive disease. We observed 627 first flares (54.7% of patients) with median active joint count of 1, physician global assessment (PGA) of 12 mm and duration of 27 weeks. Within a year after attaining inactive disease, the probability of flare was 42.5% (95% CI 39% to 46%) for any flare and 26.6% (24% to 30%) for a significant flare. Within a year after stopping treatment, it was 31.7% (28% to 36%) and 25.0% (21% to 29%), respectively. A maximum PGA >30 mm, maximum active joint count >4, rheumatoid factor (RF)-positive polyarthritis, antinuclear antibodies (ANA) and receiving disease-modifying antirheumatic drugs (DMARDs) or biological agents before attaining inactive disease were associated with increased risk of flare. Systemic JIA was associated with the lowest risk of flare. In this real-practice JIA cohort, flares were frequent, usually involved a few swollen joints for an average of 6 months and 60% led to treatment intensification. Children with a severe disease course had an increased risk of flare. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Annals of the rheumatic diseases 05/2015; DOI:10.1136/annrheumdis-2014-207164 · 10.38 Impact Factor
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    ABSTRACT: Systemic lupus erythematosus (SLE) is characterized by increased cardiovascular risk in adult-onset and childhood-onset SLE (cSLE). Type I interferons (IFNs) appear to play a prominent role in premature vascular damage in adult SLE, at least in part, by inducing impairments in the phenotype and function of endothelial progenitor cells (EPCs), thereby hampering vascular repair. It is not clear if EPC dysfunction is present in cSLE in association with a type I IFN signature. Phenotype and numbers of EPCs were quantified in patients with cSLE, juvenile idiopathic arthritis (JIA), and matched healthy controls (HC). In a separate cohort of cSLE subjects, markers of subclinical atherosclerosis and endothelial dysfunction were quantified using standardized protocols, and analyzed for associations with type I IFN serum activity. EPC numbers and function were significantly decreased in cSLE as compared to JIA and HC. cSLE serum impaired HC EPC differentiation into mature endothelial cells, an effect blocked by type I IFN pathway inhibition. Type I IFN serum activity was not significantly associated with subclinical atherosclerosis and endothelial function in cSLE. As in adults, cSLE is characterized by phenotypic and functional EPC abnormalities, likely triggered by type I IFNs. While cross-sectional analysis detected no global association between type I IFN signatures and vascular measures of subclinical atherosclerosis, longitudinal assessments are needed to evaluate if progression of vascular damage in cSLE is associated with type I IFNs as in the adult population. This article is protected by copyright. All rights reserved. © 2015 American College of Rheumatology.
    Arthritis and Rheumatology 04/2015; DOI:10.1002/art.39149
  • E V Rozenblyum · D M Levy · U Allen · E Harvey · D Hebert · E D Silverman
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    ABSTRACT: Cytomegalovirus (CMV) is a beta-herpesvirus and antibodies to this virus are common in patients with systemic lupus erythematosus (SLE). However, few studies have examined the relationship between CMV infection and SLE. Our objectives were: 1) to determine the prevalence of CMV infection at the time of SLE diagnosis, and 2) to determine the risk factors for CMV infection. A database review of 670 patients with pediatric SLE (pSLE) seen over a 20-year period identified seven patients with a CMV infection detected at the time of diagnosis of SLE. CMV was diagnosed by serology, urine and bronchoalveolar lavage. Clinical manifestations, laboratory findings, virology studies and treatments were reviewed. CMV infection was detected in seven patients at the time of SLE diagnosis (1.04% of total cohort): six were female: mean age was 13 years. Predominant features included non-Caucasian ethnicity (p < 0.01 as compared to total SLE cohort), persistent fevers on prednisone in seven and nephrotic syndrome in four. Laboratory findings included: anemia in seven, lymphopenia in five, elevated liver enzymes in four, with anti-dsDNA and anti-RNP antibodies present in six and five, respectively. Six patients received ganciclovir and CMV hyperimmune globulin (Cytogam®) with the continuation of prednisone during CMV treatment. Six of seven fully recovered without sequelae (one without treatment) but one patient died with active CMV infection. There were 1.04% of patients with pSLE who developed CMV infection. All were of non-Caucasian ethnicity. Persistent fever despite prednisone, with concomitant anemia, may be additional clues to CMV infection in pSLE. We suggest all patients have routine testing for CMV immunity at initial presentation of pSLE. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
    Lupus 01/2015; 24(7). DOI:10.1177/0961203314565443 · 2.48 Impact Factor
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    ABSTRACT: Objective: To evaluate the influence of ethnicity on self-reported health related quality of life (HRQOL) in the Canadian childhood-onset systemic lupus Erythematosus (cSLE) population.Methods: Patients with cSLE at 4 pediatric centers were consecutively enrolled. Sociodemographics and multiple disease activity measures were collected. The Child Health Questionnaire (CHQ) was administered and analysed by ethnicity.Results: We enrolled 213 cSLE patients, and complete data from 196 patients with these ethnicities were analysed: White (33%), Asian (32%), South Asian (16%), Black (11%), Latino/Hispanic (5%), and Aboriginal (4%). Compared to healthy children, cSLE patients rated their HRQOL significantly more poorly in 9 of 10 individual domains, and in 4 of 10 domains when compared to a cohort of juvenile arthritis. Within the cSLE cohort, CHQ scores were lower in 5 of 10 domains in white patients versus nonwhite ethnicities (p<0.05 for each). Physical summary scores (PhS) were lower for white patients compared to the other ethnicities aggregated together (46.0 ± 11.9 vs. 50.4 ± 10.1, p = 0.009); however, psychosocial summary scores (PsS) were similar among the groups (40.5 ± 14.6 vs. 42.8 ± 12.7, p = 0.26). Disease activity measures, including Systemic Lupus Disease Activity Index, Systemic Lupus Activity Measure and physician global visual analogue scale were similar across ethnicities. However, patient reported Systemic Lupus Activity Questionnaire symptom scores were greater in patients of white ethnicity compared to those of Asian ethnicity (8.2 ± 5.8 vs. 4.5 ± 4.7, p=0.004).Conclusion: The self- and parent-reported health status of Canadian cSLE patients differed across ethnicities, with white patients reporting lower HRQOL, despite similar and overall low disease activity. © 2014 American College of Rheumatology.
    12/2014; 66(12). DOI:10.1002/acr.22363
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    ABSTRACT: Objective: Prognosis studies examine outcomes and/or seek to identify predictors or factors associated with outcomes. Many prognostic factors have been identified in Systemic Lupus Erythematosus (SLE) but few have been consistently found across studies. We hypothesized that this is due to lack of rigor of study designs. This study aimed to systematically assess the methodological quality of prognosis studies in SLE.Methods: A search of prognosis studies in SLE was performed using MEDLINE and EMBASE, from January 1990 to June 2011. A representative sample of 150 articles was selected using a random number generator and assessed by 2 reviewers. Each study was assessed by a risk-of-bias tool according to 6 domains: study participation, study attrition, measurement of prognostic factors, measurement of outcomes, measurement/adjustment for confounders and appropriateness of statistical analysis. Information about missing data was also collected.Results: A cohort design was used in 71% of studies. High risk of bias was found in 65% for confounders, 57% of studies for study participation, 56% for attrition, 36% for statistical analyses, 20% for prognostic factors and 18% for outcome. Missing covariate or outcome information was present in half of the studies. Only 6 studies discussed reasons for missing data and 2 imputed missing data.Conclusions: Lack of rigorous study design— especially in addressing confounding, study participation and attrition, and inadequately handled missing data— has limited the quality of prognosis studies in SLE. Future prognosis studies should be designed with consideration of these factors to improve methodological rigor. © 2014 American College of Rheumatology.
    10/2014; 66(10). DOI:10.1002/acr.22322
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    ABSTRACT: To determine the most effective immunosuppressive therapy for the longterm management of proliferative lupus nephritis (PLN) based on the outcome of renal failure. A systematic review of randomized controlled trials (RCT) was conducted. MEDLINE and EMBASE were searched. RCT designed to examine the maintenance treatment effectiveness of immunosuppressive agents for PLN were included. A Bayesian network metaanalysis of 2-arm and 3-arm trials was used. A skeptical prior assumption was used in sensitivity analysis. Four immunosuppressive agents were evaluated: cyclophosphamide (CYC), azathioprine (AZA), mycophenolate mofetil (MMF), and prednisone alone. The outcome of interest was renal failure during the study period, defined by serum creatinine (sCr) > 256 μmol/l, doubling of sCr from baseline, and/or endstage renal disease. The OR (95% credible interval) of developing renal failure at 2-3 years was 0.72 (0.11, 4.49) for AZA versus CYC, 0.32 (0.04, 2.25) for MMF versus CYC, 2.40 (0.22, 36.94) for prednisone alone versus CYC, and 0.45 (0.11, 1.48) for MMF versus AZA. The probability (95% credible interval) of developing renal failure at 2 years as expected for each agent was 6% (0.7%, 24%) for MMF, 12% (2%, 37%) for AZA, 16% (5%, 33%) for CYC, and 31% (5%, 81%) for prednisone alone. After applying a skeptical prior in the Bayesian analysis, there was no evidence of benefit for 1 therapy over another. Although the data suggest that MMF may be superior to other treatments for the maintenance treatment of PLN, the evidence is not conclusive.
    The Journal of Rheumatology 09/2014; 41(10). DOI:10.3899/jrheum.140050 · 3.17 Impact Factor
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    ABSTRACT: Key Clinical Message Systemic lupus erythematosus should be included in the differential diagnosis of every adolescent with pancytopenia. An accurate diagnosis with the appropriate therapy is vital and can cause lasting reversal of this condition. Systemic lupus erythematosus should be included in the differential diagnosis of every adolescent with pancytopenia. An accurate diagnosis with the appropriate therapy is vital and can cause lasting reversal of this condition.
    09/2014; 2(6). DOI:10.1002/ccr3.123
  • E.N. Kelly · R Sananes · C Chiu‐Man · E.D. Silverman · E Jaeggi
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    ABSTRACT: Objective: To determine the impact of prenatal exposure to maternal anti-Ro antibodies, slow fetal heart rate and/or chronic dexamethasone therapy for immune-mediated congenital atrio-ventricular heart block (CAVB) on cognitive and academic performance at school age.Methods: Prospective, blinded assessment of cognitive functioning of 3 cohorts of children aged 6-16 years with in-utero exposure to maternal anti-Ro antibodies and with: 1) no CAVB and no prenatal dexamethasone (n=14); 2) CAVB without prenatal treatment (n=10); and 3) CAVB with prenatal dexamethasone therapy (n=16). Domains assessed included intelligence, visual perceptual and visual motor skills, auditory and visual attention, verbal learning and memory, visual memory, executive function and behavior.Results: All cohorts scored within the normal range and were not significantly different in intelligence scores, verbal comprehension, perceptional reasoning, working memory, and processing speed. For prenatally treated children with CAVB, there were no significant associations between neurocognitive function scores, minimal fetal heart rate (range: 47 – 80 beats/min) and the duration and dosage (2-15 weeks; 56 – 824 mg) of dexamethasone therapy.Conclusion: CAVB and transplacental prenatal treatment with dexamethasone was not associated with neurocognitive impairment in school-age children. Larger numbers are required to validate our observation and assessment of other cognitive abilities is warranted. © 2014 American College of Rheumatology.
    Arthritis and Rheumatology 08/2014; 66(8). DOI:10.1002/art.38675
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    ABSTRACT: Studies of paediatric patients with membranous lupus nephritis (MLN) have yielded variable results, mostly due to the inclusion of mixed, i.e. proliferative nephritis. The aim of this study was to describe clinical and laboratory findings at the diagnosis of paediatric non-proliferative MLN, report the outcome and identify predictors of remission.
    Pediatric Nephrology 07/2014; 30(1). DOI:10.1007/s00467-014-2908-2 · 2.88 Impact Factor
  • 69th Annual Meeting of the Canadian-Rheumatology-Association (CRA); 07/2014
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    ABSTRACT: Objective To describe clinical outcomes of juvenile idiopathic arthritis (JIA) in a prospective inception cohort of children managed with contemporary treatments. Methods Children newly diagnosed with JIA at 16 Canadian paediatric rheumatology centres from 2005 to 2010 were included. Kaplan–Meier survival curves for each JIA category were used to estimate probability of ever attaining an active joint count of 0, inactive disease (no active joints, no extraarticular manifestations and a physician global assessment of disease activity <10 mm), disease remission (inactive disease >12 months after discontinuing treatment) and of receiving specific treatments. Results In a cohort of 1104 children, the probabilities of attaining an active joint count of 0 exceeded 78% within 2 years in all JIA categories. The probability of attaining inactive disease exceeded 70% within 2 years in all categories, except for RF-positive polyarthritis (48%). The probability of discontinuing treatment at least once was 67% within 5 years. The probability of attaining remission within 5 years was 46–57% across JIA categories except for polyarthritis (0% RF-positive, 14% RF-negative). Initial treatment included joint injections and non-steroidal anti-inflammatory drugs for oligoarthritis, disease-modifying antirheumatic drugs (DMARDs) for polyarthritis and systemic corticosteroids for systemic JIA. Conclusions Most children with JIA managed with contemporary treatments attain inactive disease within 2 years of diagnosis and many are able to discontinue treatment. The probability of attaining remission within 5 years of diagnosis is about 50%, except for children with polyarthritis.
    Annals of the Rheumatic Diseases 05/2014; DOI:10.1136/annrheumdis-2014-205372 · 10.38 Impact Factor
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    ABSTRACT: Objective Epidemiological associations suggest vitamin D may play a role in inflammation and atherosclerosis. Using frozen serum and data from the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) trial, we assessed associations between 25-hydroxyvitamin D [25(OH)D] and measures of systemic lupus erythematosus (SLE) disease activity and cardiovascular risk. Methods Baseline APPLE serum samples were used to measure 25(OH)D levels. Logistic regression models for vitamin D deficiency [25(OH)D levels <20 ng/mL] were constructed using baseline variables collected as part of the trial, including race, season, latitude, disease duration, disease activity, high-sensitivity C-reactive protein (hsCRP), proteinuria, fasting lipids and carotid intima medial thickness (CIMT). Results Samples were available from 201 of 221 APPLE subjects; 61/201 (30%) had vitamin D deficiency at baseline. In univariable analysis, baseline vitamin D deficiency was associated with season (p<0.01), minority status (p<0.01), body mass index (p=0.04), duration of SLE (p<0.01), SLICC damage index (p=0.04), hsCRP (p<0.01), mean–max CIMT (p=0.01), LDL-cholesterol (p=0.03) and timed urine protein (p=0.03). In multivariable modelling, vitamin D deficiency was associated with age, latitude, season, minority status, proteinuria and hsCRP. Conclusions Vitamin D deficiency is common in paediatric lupus and is independently associated with elevated hsCRP, a marker of inflammation that predicts cardiovascular disease risk. Although association is not proof of causation, this association is novel in the paediatric SLE population and suggests that vitamin D deficiency may contribute to heightened inflammation and cardiovascular risk in this population. Trial register number NCT00065806.
    05/2014; 1(1):e000011. DOI:10.1136/lupus-2014-000011
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    ABSTRACT: Background/Purpose:Biologic therapies have revolutionized the management of rheumatic diseases of childhood. However, these medications are associated with adverse effects including the possible development of neoplasms. The aim of our study was to determine the rate as well as risk factors for the development of neoplasms in patients with JIA treated with biologics.Methods:We performed a retrospective review of the rheumatology biologic registry (RBR) at The Hospital for Sick Children (SickKids), Toronto, Canada, one of the largest quarternary pediatric referral centres in North America. Demographic and neoplastic data, clinical course and medication history were extracted from the RBR and clinical charts. Unless specified, data was expressed as median (IQR). The study was approved by the SickKids Ethics Review Board.Results:The cohort consisted of 357 patients with rheumatic diseases who were on one or more biologics between January 1997 and August 2013. Juvenile Idiopathic Arthritis (JIA) was the most common diagnosis [302/357 (84.5%)]. A total of 6/357 (1.68%) patients developed a neoplasm: 4 with JIA, 1 each with idiopathic uveitis and polyarteritis nodosa. (Refer to t87) 1Table 1. Patient 1Patient 2Patient 3Patient 4Patient 5Patient 6NeoplasmNasopharyngeal carcinoma1. Tonsillar lymphoproliferative disorder (LD) in 2006Clear cell renal carcinomaHepatosplenic lymphomaSmall blue cell sarcoma, undifferentiatedPilomatricoma 2. Renal carcinoma in 2011 Rheumatic Disease (RD)Idiopathic UveitisPolyarteritis NodosaPoly JIA (RF negative)Systemic JIAOligo JIA (extended)Oligo JIA (extended)Age of onset of RD (years)10.81.18.24.71.62.0SexMaleMaleFemaleFemaleFemaleFemaleDMARD(s), Cytotoxic agentsMTX (4.7)MTX (1.2);MTX (6.2);MTX (3.6);MTX (7.2);CSA (3.2);(Time (years)) AZA (NA);LFN(0.2);CSA (0.9);LFN (0.2)AZA (4.3);Abbreviations: -Methotrexate (MTX), CYC (1.5)CSA (1.5);Tacrolimus (5.0); MTX (6.0);-Azathioprine (AZA), AZA (1.2);Etoposide (6 cycles over 34 days); LFN (2.8)-Leflunomide (LFN), SSA (0.9)Thalidomide (0.6) Cyclophosphamide (CYC), -Cyclosporine (CSA), -Sulfasalazine (SSA) -Not available (NA) Biologic(s)Infliximab (3.3)Infliximab (7.5)Etanercept (4.8)Etanercept (0.1);Etanercept (5.2)Infliximab (8.2);(Time (years)) Infliximab (1.7); Etanercept (1.5) Anakinra (1.9) Time to neoplasm (years)5.31. 14.115.811.816.712.7 2. 18.6 Time from DMARD to neoplasm (years)4.71. 6.817.611.88.412.6 2. 11.4 Time from Biologic to neoplasm (years)3.31. 4.810.68.65.31.3 2. 9.3 Family history of neoplasmMaternal grandfather: lung cancer; Maternal grandmother: cervical cancerMother died due to breast cancer.NANANAStrong family history of colon cancerAmongst patients with neoplasms, the median (IQR) age at rheumatic disease onset was 3.4 (1.7–7.3) years and the age of diagnosis of the neoplasm was 16.3 (15.3–17.9) years. All cancers were malignant except in patient 6 which was of a benign nature. On average, patients had exposure to 3 DMARDs (range 1–5), with methotrexate as the commonest DMARD used in 5/6 patients prior to diagnosis of the neoplasm. The time from the disease onset to initiation of DMARD was 3.9 (0.4–7.9) years. The time from the DMARD initiation and the diagnosis of a neoplasm was 10.1 (7.2–12.3) years. For methotrexate alone, the duration of use was 5.4 (3.9–6.1) years. All patients diagnosed with a neoplasm, had received both, DMARD(s) and biologic(s). 2 patients were on infliximab alone, 2 on etanercept alone and 2 on multiple biologics of which etanercept and infliximab were both used. The time between onset of a biologic and diagnosis of a neoplasm was 5.0 (3.6–7.7) years. Two patients (2 and 4) also received medications which are associated with the development of the neoplasms (cyclophosphamide or etoposide).Conclusion:Majority of neoplasms were of uncommon morphology and site as well as aggressive in nature. The neoplasms developed late after drug exposure with a median duration to diagnosis of neoplasm of 10.1 years on a DMARD and 5.5 years on a biologics. Whilst DMARDs and biologics are effective for the management of rheumatic diseases, patients with refractory disease requiring ongoing drug therapies should have malignancy/ neoplasm surveillance included as part of routine clinical care. Comparison of patients on biologics with and without neoplasms is in progress.
    Arthritis and Rheumatology 03/2014; 66(S11). DOI:10.1002/art.38596
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    ABSTRACT: Background/Purpose:To assess efficacy and safety of SC golimumab (GLM) in polyarticular pediatric juvenile idiopathic arthritis pts (aged 2 to <18 yrs) with active arthritis despite MTX for ≥3 months.Methods:In GO-KIDS, a 3-part randomized double-blind, PBO-controlled, withdrawal trial in pts with active JIA with a polyarticular course (≥5 active joints) and disease duration of ≥6 months despite current MTX (10–30 mg/m2/wk). In Part 1(wk 0–12), all pts received open-label (OL) 30 mg/m2 GLM SC (max 50 mg) q4 wks with stable MTX dose. At wk 16, pts with ACR JIA 30 response entered Part 2 (wk 16–48). In Part 2, pts were randomized to continue GLM or switch to PBO q4 wks. Upon Part 2 completion at wk 48 or ACR JIA flare in Part 2, pts received OL GLM in Part 3. Primary endpoint was proportion of ACR JIA 30 responders at wk 16 without a JIA flare in Part 2 using wk 16 as baseline measurement. Secondary outcomes were ACR JIA 30/50/70/90 response rates and inactive disease rates at wk 16 and wk 48 by group and safety.Results:173 pts (Caucasian 87.9%, 75.7% females; age [median/range] 12 yrs/2–17 yrs) with moderately active disease were enrolled (Table 1); 19 (11%) were d/c in Part 1 (lack of efficacy n = 14, AE n = 4, withdrawal of consent n = 1). In Part 1, 151 of 173 (87.3%) achieved an ACR JIA 30 response and 36.1% inactive disease status (Table 2). There were 154 pts randomized double-blind in Part 2 (PBO n = 76; continued GLM n = 78). At the end of Part 2, no significant differences between groups in JIA ACR non-flare rates and trial did not meet primary endpoint [PBO-grp vs. GLM-grp: 52.6% vs. 59.0%, p = 0.41) nor were there differences for major secondary endpoints (Table 2). In contrast, sustained response in both groups (PBO, GLM) relative to wk 0 (Table 1 and 2). 6.5% (10 of 154) of pts d/c therapy after wk16 through wk 48. Through wk 48, AEs, serious AE (SAE), and serious infections were reported in 87.9%, 13.3%, and 2.9% of all randomized pts, respectively. Most common SAE was JIA exacerbation. No deaths, active TB or malignancies were reported (1). GLM-treated pt experienced SAE of toxic hepatitis and 1 had SAE of hepatic enzyme increase. One pt switched from PBO to GLM experienced SAE of serum sickness reaction, resulting in GLM d/c. Proportion of pts with ≥1 injection site reaction was 8.1%. None of the reactions were serious, severe, or led to GLM d/c.Table 1. At Baseline (All enrolled patients n=173)At wk16 (All randomized patients prior to randomization, n=154)At wk48Values are medians (interquartile range)PBO + MTX (n=76)GLM + MTX (n=78) Physicians global assessment5.40 (3.90; 7.00)0.50 (0.10; 1.30)0.30 (0.00; 1.00)0.30 (0.00; 1.30)Patient/parent global assessment4.50 (2.80; 6.10)0.90 (0.30, 2.30)0.60 (0.20; 1.65)0.45 (0.10; 1.70)Number of active joints12.0 (8.0; 18.0)1.0 (0.0; 3.0)1.0 (0.0; 3.0)0.0 (0.0; 2.0)Number of joints with limited range of motion8.0 (6.0; 15.0)1.0 (0.0, 4.0)0.5 (0.00; 4.0)1.0 (0.0; 3.0)Physical function by CHAQ0.94 (0.38; 1.50)0.25 (0.00; 0.75)0.13 (0.00; 0.63)0.00 (0.00; 0.63)ESR (mm/hr)16.00 (8.00; 28.00)9.00 (5.00; 19.00)9.50 (5.00; 16.50)10.00 (5.00; 19.00)Methotrexate (mg/wk)15t(5.00; 30.00)15t(5.00; 30.00)15t(5.00; 30.00)15t(5.00; 30.00)Table 2. ACR JIA response and flare ratesPART 1 [WK 0ndash;16] Pts experiencing flares/those considered treatment failures due to protocol violations are considered ACR non-responders from the flair/failure visit to wk 48aObserved dataPercentage of ACR JIA responders at end of Part 1 [WK 16] (n = 173)JIA ACR 3087.3%t(151) JIA ACR 5079.2%t(137) JIA ACR 7065.9%t(114) JIA ACR 9036.4%t(63) Inactive disease36.1%t(62) PART 2 [WK 16ndash;48] Percentage of ACR JIA 30 responders without flare in Part 2 (n = 154)PBO + MTX (n=76)52.6%t(40)P=0.41 GLM + MTXt(n=78)59.0%t(46) Inactive disease21.6%/39.7% Clinical remission11.8%/12.8% Percentage of ACR JIA responders at WK48 (vs. wk0) by treatment in Part 2‡ [PBO +MTX/GLM +MTX]JIA ACR 3095.9%/89.0% JIA ACR 5091.8%/86.3% JIA ACR 7078.1%/78.1% JIA ACR 9053.4%/56.2% Conclusion:JIA pts with active polyarticular dis ease demonstrated rapid response to GLM with 16 wks of OL treatment, resulting in inactive disease in 36% of the pts. The lack of differences in flare rates between GLM and PBO arms from wk 16 to 48 among OL GLM responders needs further evaluation. Safety profile was acceptable and injections well tolerated.
    Arthritis and Rheumatology 03/2014; 66(S11). DOI:10.1002/art.38569

Publication Stats

9k Citations
1,448.34 Total Impact Points

Institutions

  • 1989–2015
    • SickKids
      • • Division of Rheumatology
      • • Division of Cardiology
      • • Department of Paediatrics
      • • Department of Diagnostic Imaging
      Toronto, Ontario, Canada
    • Yale-New Haven Hospital
      New Haven, Connecticut, United States
    • The University of Calgary
      • Faculty of Medicine
      Calgary, Alberta, Canada
  • 1988–2015
    • University of Toronto
      • • Hospital for Sick Children
      • • Department of Paediatrics
      • • Division of Rheumatology
      • • Laboratory Medicine Program
      Toronto, Ontario, Canada
  • 2009
    • The University of Chicago Medical Center
      Chicago, Illinois, United States
    • University of Oklahoma Health Sciences Center
      • Department of Pediatrics
      Oklahoma City, Oklahoma, United States
    • University Health Network
      Toronto, Ontario, Canada
  • 2007–2009
    • IRCCS Istituto G. Gaslini
      Genova, Liguria, Italy
  • 1993–2006
    • Dalhousie University
      • Department of Pediatrics
      Halifax, Nova Scotia, Canada
    • University of Texas Health Science Center at Houston
      • Department of Internal Medicine
      Houston, Texas, United States
  • 1996
    • University of Saskatchewan
      • Department of Pediatrics
      Saskatoon, Saskatchewan, Canada
    • University of Ottawa
      • Department of Pediatrics
      Ottawa, Ontario, Canada
  • 1992–1996
    • Toronto Western Hospital
      Toronto, Ontario, Canada
  • 1995
    • Stockholm University
      Tukholma, Stockholm, Sweden
  • 1985
    • Stanford Medicine
      Stanford, California, United States
    • Stanford University
      Palo Alto, California, United States
  • 1984
    • Children's Hospital Los Angeles
      Los Angeles, California, United States