Karen Onel

University of Illinois at Chicago, Chicago, Illinois, United States

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Publications (51)106.54 Total impact

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    ABSTRACT: This study evaluated the effects of obesity on health-related quality of life (HRQOL) measures in juvenile-onset systemic lupus erythematosus (jSLE).
    Lupus 10/2014; · 2.78 Impact Factor
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    ABSTRACT: Objective: Few data are available regarding the rates of serious adverse events and important medical events (SAEs, IMEs) outside of product based registries and clinical trials for juvenile idiopathic arthritis (JIA). The Enhanced Drug Safety Surveillance Project (EDSSP) was developed to pilot a novel system to collect SAE/IMEs in children with JIA. This analysis reports the results from this 4-year (2008-2012) EDSSP. Methods: Participating physicians were surveyed monthly to ascertain whether their JIA patients experienced a SAE or IME. Sites were surveyed every 6 months to determine the number of unique JIA patients seen at each site during that 6-month period. Reporting rates were calculated per 100 person-years (p-y) and 95% confidence intervals (CI) were calculated based on a Poisson distribution. Results: Thirty-seven CARRA sites with 115 physicians participated. The average response rate to the monthly surveys was 65%. There were 147 total SAEs and 145 IMEs. The largest proportion of SAEs and IMEs occurred in children with polyarticular JIA (39% and 37%). The majority of SAEs and IMEs were reported for patients receiving biologic therapies (76% and 69%). The total event rate for SAEs and IMEs combined was 1.07 events per 100 p-y (95% CI: 0.95-1.19). The rates for SAEs and IMEs were 0.54 per 100 p-y (95% CI: 0.45-0.63) and 0.53 per 100 p-y (95% CI: 0.49-0.62). Conclusion: The EDSSP provided a simple tool for SAE/IME reporting within an established research network and resulted in a similar range of reported events as captured by a traditional product-based registry. © 2014 American College of Rheumatology.
    Arthritis care & research. 10/2014;
  • Arthritis Care & Research. 04/2014;
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    ABSTRACT: Background/Purpose:Children with JIA experience more pain and disordered sleep than healthy children. JIA and poor sleep are associated with particular cytokine abnormalities, and the correlation between the two and how they relate to a patient's pain perception have not been studied. Elevation in TNF-a, IL-6, IL-17, and IFN-g have been found in the serum of children with JIA during active disease. Levels of proinflammatory cytokines are also increased during sleep loss. Indeed, blocking TNF-a has been shown in adults with RA to improve sleep the night after the first dose. We hypothesize that dysfunctional sleep enhances pain in our patients and may be associated with abnormal cytokine profiles. In this pilot study, we hope to identify a subgroup of children with JIA that could benefit from intervention in improving sleep patterns.Methods:We plan to enroll 60 patients with JIA. Sleep is assessed by the sleep self-report (SSR), the children's sleep habits questionnaire (CSHQ), and actigraphy. Good concordance in measurements of sleep duration has been established between PSG and actigraphy. Patients wear an actigraphy watch and keep a daily sleep and pain diary for 14 days. Disease activity is assessed using ESR, sum of active joints, patient/parent and physician global assessment of disease activity. Serum cytokine testing will be performed by flow cytometry.Results:31 patients are enrolled. We identified 7 children with disordered sleep using CSHQ/ SSR. These patients report having pain on most days, and they trend toward having elevated disease activity (increased physician and patient global assessments as well as number of active joints, ESR was non-contributory). To date, 9 of the 31 patients underwent actigraphy. Preliminary data does not indicate an association between disease activity and objective sleep dysfunction. There is not yet enough data to comment on the association of pain and disordered sleep in the absence of disease activity. Serum from 22 patients has been collected for cytokine studies.Conclusion:There is a trend toward an association of perceived poor sleep (as reported subjectively by SSR/CSHQ) with increased pain and disease activity in our patient population. Increased disease activity does not appear to be objectively related to disordered sleep using actigraphy, however. So far, actigraphy has been conducted on patients without subjective complaints of sleep dysfunction. We plan to collect more objective data (via actigraphy) on patients with subjective sleep complaints (with and without active disease) to better characterize the relationship of pain and sleep. When this has been accomplished, we plan to investigate cytokine profiles in these groups.
    Arthritis & Rheumatology. 03/2014; 66(S11).
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    ABSTRACT: Background/Purpose:In the phase 3 TENDER trial of tocilizumab (TCZ) in patients with systemic juvenile idiopathic arthritis (sJIA), decreases in neutrophil count were commonly observed. The purpose of this study was to determine whether neutropenia was associated with increased risk for infection and to investigate variables associated with the development of neutropenia in patients treated with TCZ for up to 2 years in TENDER.Methods:One hundred twelve children with active, persistent sJIA were randomly assigned 2:1 to receive TCZ based on body weight (12 mg/kg <30 kg or 8 mg/kg ≥30 kg) or placebo intravenously every 2 weeks for 12 weeks and continued in an ongoing, TCZ openlabel extension (). Worst Common Toxicity Criteria (CTC) neutropenia grade (grade 1, ≥1.5 and <2.0 × 109/L; grade 2, ≥;1.0 and <1.5 × 109/L; grade 3, ≥0.5 and <1.0 × 109/L; grade 4, <0.5 × 109/L) and lowest observed neutrophil count (109/L) were identified for each patient. Univariate linear regression analysis was performed to investigate the association of patient characteristics with lowest observed neutrophil count. Rates of infection and serious infection (per 100 patient-years [PY]) in periods ±15 days around grade 1–2 neutropenia (22.9 PY) and around grade 3–4 neutropenia (5.5 PY) were compared with corresponding rates in periods with normal neutrophil count (173.6 PY).Results:Up to week 104, 64 of 112 patients (57.1%) had at least 1 episode of grade 1–4 neutropenia; worst grade: 1 (n = 2), 2 (n = 34), 3 (n = 26), and 4 (n = 2). Rates of infection and serious infection during periods of normal neutrophil counts (276.5/100 PY [95% CI: 252.3, 302.3] and 11.5/100 PY [95% CI: 7.0, 17.8], respectively) were comparable with those observed ±15 days around grade 1–2 neutropenia (226.7/100 PY [95% CI: 169.3, 297.3]; 8.7/100 PY [95% CI: 1.1, 31.5]) and grade 3–4 neutropenia (292.5/100 PY [95% CI: 167.2, 475.0]; 0/100 PY), with no trend toward increased risk with higher grade neutropenia. Methotrexate use (Yes/No) was significantly associated with lowest observed neutrophil count (difference: −0.575 [95% CI: −1.02, −0.13], p = 0.012), with 62% of 77 patients receiving methotrexate versus 46% of 35 patients not receiving methotrexate having grade 1–4 neutropenia. Younger age was borderline associated with lowest observed neutrophil count (β = 0.04661; p = 0.047). Concurrent use of glucocorticoids and TCZ exposure were not associated with lowest observed neutrophil count (p > 0.3).Conclusion:No trend for association between neutropenia and increased risk for infection was observed in the TENDER trial. Background methotrexate, and somewhat younger age, was associated with increased risk for neutropenia, whereas TCZ exposure and concurrent glucocorticoid use were not.
    Arthritis & Rheumatology. 03/2014; 66(S11).
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    ABSTRACT: Background/Purpose:The nuclear oncoprotein DEK is a biochemically distinct protein, modulating heterochromatin integrity, chemoattractant of neutrophils and T-cells and vital for the formation of neutrophil extracellular traps (NETs). NETs are important for resolution of inflammation suggesting that DEK contributes to the development of autoimmune diseases. High levels of DEK autoantibodies have been found in several autoimmune diseases including juvenile idiopathic arthritis (JIA) but their role in disease pathogenesis is not clear. Since DEK and DEK autoantibodies can contribute to the development of immune complexes and NET formation we suggest that DEK antibody levels can predict flare with the discontinuation of anti-TNF therapy.Methods:In16 pediatric rheumatology centers, sera samples were collected from 137 children with polyarticular JIA with clinically inactive disease (CID) on anti-TNF therapy. The therapy was stopped and disease activity was monitored for at least 8 months or until disease flare. DEK antibody levels were measured in sera collected at time of enrollment and 6 months (when anti-TNF therapy was stopped) by ELISA. DEK antibody levels relative to healthy controls were calculated by area under the curve (AUC), expressed as unit-free ratios.Results:103 females and 34 males patients were enrolled. Mean age 11.3 years and disease duration 5.0 years. JIA included: 13% extended oligoarthritis, 74% polyarthritis rheumatoid factor (RF) negative and 12 % polyarthritis RF positive and 46% positive ANA. 77% were taking etanercept, 18% adalimumab, 5% infliximab and 40% methotrexate. 31 patients (23%) discontinued the study prior stopping the therapy for various reasons, including loss of CID. Of 106 subjects who stopped the therapy, 39 (37%) flared within 8 months (mean of 104.8 days). 67 subjects (63%) had no flares within 8 months after stopping the therapy. 71 out of 106 patients samples were analyzed thus far for DEK antibody levels. DEK antibody level ratios compared to healthy controls was −0.36 (some patients had lower antibody levels than did healthy controls) to 1.41, median ratio of 0.11 (Q1–Q3 of 0.09–0.24) and 0.13 (SD, 0.3). High levels of DEK antibodies, mean and SD of 0.209 ± 0.36 were detected in the 21 patients that flared within 8 months compared to lower levels of DEK antibodies (0.09 ± 0.27) in 50 patients with CID for at least 8 months (ANOVA P= 0.1832). Negative correlation was observed between the days to flare and DEK antibody levels (spearman rho = −0.31, P = 0.07), suggesting that when therapy stopped, patients with higher levels of DEK antibodies will flare sooner with estimated odds ratio of 3.3 (95% CI, 0.61, 18.0), suggesting that each unit increase in DEK antibodies is associated (P = 0.17) with more than a 2-fold increased risk of flare within 8 months.Conclusion:In children with JIA extended oligoarthritis and polyarthritis on anti-TNF therapy that maintain CID for at least 6 months while on therapy, high DEK antibody levels may be correlated with flare within the first 8 months after stopping the therapy. This study suggests that DEK antibody levels can predict the outcome of discontinuation of anti-TNF therapy, although more patient samples need to be analyzed from this study and future studies.
    Arthritis & Rheumatology. 03/2014; 66(S11).
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    ABSTRACT: Background/Purpose:Tocilizumab (TCZ) treatment has been associated with reduced neutrophil counts in adults with rheumatoid arthritis and in children with systemic juvenile idiopathic arthritis. The aims of this study were to assess changes in neutrophil counts, determine whether neutropenia was associated with increased risk for infection, and investigate variables associated with the development of neutropenia in patients with polyarticular-course juvenile idiopathic arthritis (pcJIA) receiving TCZ for up to 2 years in the CHERISH trial.Methods:One hundred eighty-eight patients (2–17 years) with active pcJIA and inadequate response to methotrexate received open-label (OL) TCZ according to body weight (BW) (BW ≥30 kg, TCZ 8 mg/kg; BW <30 kg, randomly assigned 1:1 to TCZ 8 or 10 mg/kg) every 4 weeks for 16 weeks. Patients who achieved ≥JIA ACR30 response at 16 weeks entered a 24-week, randomized, double-blind withdrawal period and were assigned 1:1 to placebo or continued TCZ. Patients who experienced JIA ACR flare or who completed the withdrawal period entered an OL extension through week 104. Blood cell counts were monitored every 4 weeks. Worst Common Toxicity Criteria (CTC) neutrophil grade and lowest observed neutrophil count (109/L) were identified for each patient. Rates of infection and serious infection (per 100 patient-years [PY]) in periods ±30 days around grade 1/2 and around grade 3/4 neutrophil counts were compared with corresponding rates in periods with normal neutrophil counts. Univariate linear regression analysis was used in patients enrolled in part 3 of the study to investigate the association between patient baseline characteristics and lowest observed neutrophil count from baseline to week 104.Results:At baseline, all patients had neutrophil counts within or above the normal range. Median neutrophil count decreased during the first 16 weeks of treatment and stabilized for the remainder of the study. Throughout the 2-year study, 118 patients (62.8%) had normal neutrophil counts, whereas CTC grades 1, 2, 3, and 4 neutrophil counts were reported in 15 (8.0%), 44 (23.4%), 11 (5.9%), and 0 (0.0%) patients, respectively. Infections and serious infections occurred at rates of 151.4/100 PY and 5.2/100 PY, respectively. All serious infection events (n = 16) occurred during periods of normal neutrophil count. Rates of infection during periods of normal, grade 1/2, and grade 3 neutrophil count were 147.8/100 PY (95% CI, 133.9–162.7), 176.6/100 PY (95% CI, 128.8–236.3), and 340/100 PY (95% CI, 136.7–700.5), respectively, with largely overlapping confidence intervals. Low neutrophil count was not associated with any baseline covariates investigated.Conclusion:In the CHERISH trial, there was no evidence of increased rates of serious infection associated with low neutrophil count. The prevalence of neutropenia in the pcJIA population was lower than in other disease groups (eg, systemic JIA) treated with TCZ.
    Arthritis & Rheumatology. 03/2014; 66(S11).
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    ABSTRACT: Background/Purpose:Treatment with anti-TNF therapies (anti-TNF) for polyarticular forms (extended oligo, Poly RF +/−) of JIA (PF-JIA) results in >50% demonstrating clinically inactive disease (CID). The aims of this study were to determine the frequency, timing and predictors of flare upon withdrawal of anti-TNF in PF-JIA in CID.Methods:In 16 centers 137 children with PF-JIA in CID on anti-TNF were enrolled and followed for ≥14 mos. If CID was maintained for the first 6 study mos, then anti-TNF was stopped. The primary outcome variable was a validated definition of disease flare within 8 months after stopping anti-TNF. Background meds were stable. Blood for S100, DEK, DNA and RNA was drawn for current and future biomarker and genetic studies.Results:The study population included 18 (13%) extended oligarticular, 17 (12%) RF+ Poly and 102 (74%) RF- Poly JIA patients. At enrollment, age (mean/median/range) was 11.3/11.6/3.4–20.1 yrs; disease duration was 5.0/4.1/0.6–18.6 years; 103 (75%) were females and 64 (47%) were ANA+. Duration of CID at baseline was 1.2/0.5/1 day–12.1 yrs. Anti-TNF was etanercept in 106 (77%), 25 (18%) adalimumab and 6 (5%) infliximab. 40% were on MTX at baseline (mean/median dose 0.4/0.4 mg/kg/week). Other meds: 1 leflunomide, 2 hydroxychloroquine, and 1 prednisolone.31 (23%) subjects were discontinued from the study in the first 6 mos: 23 (17%) due to loss of CID, 5 (4%) med noncompliance, 2 (1%) moved/LTF, 1 (1%) ILAR subtype changed (oligo to psoriatic). For the extended oligo, Poly RF− and Poly RF+ categories 94%, 82% and 60%, respectively, maintained CID for the first 6 months (c2 6.7, p 0.03). ANA status, MTX use, and type of anti-TNF were not associated with the ability to maintain CID (c2 p values 0.48, 0.14, and 0.75, respectively).106 (77%) subjects maintained CID for the first 6 months and stopped anti-TNF as per protocol. 67/106 (63%) maintained CID for ≥8 mos off anti-TNF while 39 (37%) flared. Time without flaring after stopping anti-TNF therapy was duration from the month 6 visit to the last study visit (mean/median/range for duration of followup was 249/250/126–322 days). The mean/median/range for time to flare was 108/105/7–271 days. Time to flare (days) for etanercept was 105/105/7–271, adalimumab 119/120/28–238 and infliximab 28/28/28. Flare was seen in 47% (8/17) extended oligo, 37% (30/80) poly RF– and 11% (1/9) poly RF+ ((c2 p-value 0.19). In those on background MTX, 33% (13/40) flared at a mean of 90 days, while those not on background MTX, 39% (26/66) flared at a mean of 113 days ((c2 p-value 0.48). Using univariate analysis of variance, only weak correlations of MTX dose, disease duration, and CID duration with flare/no flare were seen (Spearman correlations −0.03, −0.17, −0.19, respectively).Conclusion:In this prospective multicenter study, 77% of the PF-JIA patients were able to maintain CID for the first 6 months on anti-TNF. Discontinuation of anti-TNF in PR-JIA (who have demonstrated on average 1.8 years of CID) resulted in a flare rate of 37% within 8 mos. Clinical parameters had only minimal predictive ability. Ongoing work includes biomarker identification and continued follow-up of the cohort.
    Arthritis & Rheumatology. 03/2014; 66(S11).
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    ABSTRACT: Background/Purpose:Treatment with anti-TNF therapies for polyarticular forms (extended oligoarthritis, rheumatoid factor [RF] +/− polyarthritis) of JIA (PF-JIA) results in up to 50% of patients (pts) demonstrating clinically inactive disease (CID). Serum S100A12 protein levels have been demonstrated to predict failure to maintain CID after withdrawal of methotrexate (MTX). This study determined the pattern of baseline serum S100A12 levels during CID on anti-TNF therapy.Methods:In 16 centers, 137 pts with PF-JIA in CID on anti-TNF therapy were enrolled. During the first 6 study months patients were maintained on anti-TNF therapy and monitored. If CID was maintained for first 6 study months, then anti-TNF therapy was stopped. Pts were followed for up to 14 mos total or until loss of CID on anti-TNF therapy or until flare off anti-TNF therapy, whichever came first. Background medications were stable throughout the study. Blood for serum S100A12 measurement was drawn at study enrollment. S100A12 measurements were obtained via a validated ELISA. The secondary outcome of this part of the analysis was failure to maintain CID during the first 6 study months.Results:7 pts were discontinued from the study for reasons other than inability to maintain CID and 130 patients were available for analysis. 24 pts failed to maintain CID during the first 6 study months. Demographic and clinical details are reported elsewhere during this conference. Baseline S100A12 levels did not differ significantly according to sex (female 96 +/− 229 ng/ml, male 66 +/− 144 ng/ml), JIA subtype (extended oligo 91 +/− 199 ng/ml, poly RF- 93 +/− 219 ng/ml, poly RF+ 114 +/− 157 ng/ml) presence of ANA (positive 83 +/− 174 ng/ml, negative 96 +/− 240 ng/ml), MTX co-therapy (yes 84 +/− 259 ng/ml, no 95 +/− 167 ng/ml) or type of anti-TNF therapy (adalimumab 114 +/− 140 ng/ml, etanercept 90 +/− 214 ng/ml, infliximab 120 +/− 330 ng/ml) (values given as median +/− standard deviation) and did not correlate with duration of previous duration of inactive disease (r = −0,06). Globally, S100A12 did not differ significantly according to failure to maintain CID (failure to maintain CID 100 +/− 188 ng/ml, maintaining CID 93 +/− 216 ng/ml). Based on a predefined normal level of S100A12 of <120 ng/ml, 87 (66%) of patients demonstrated normal S100A12 levels and 43 (33%) of patients demonstrated elevated S100A12 levels. However, receiveroperating curve analysis computing baseline S100A12 against failure to maintain CID demonstrated an areaunder-the-curve of 0,47 (95% confidence interval 0.33–0.62).Conclusion:In this prospective multicenter study, baseline S100A12 levels in pts with PF-JIA were elevated in a substantial proportion of pts but did not differ among groups according to multiple parameters. Serum S100A12 did not predict failure to maintain CID.
    Arthritis & Rheumatology. 03/2014; 66(S11).
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    ABSTRACT: Background/Purpose:Anti-TNF therapy for polyarticular forms (extended oligo-, rheumatoid factor +/− polyarthritis) of JIA (PF-JIA) results in up to 50% of patients (pts) demonstrating clinically inactive disease (CID). This study determined the pattern of serum S100A12 levels at the time of withdrawal of anti-TNF therapy.Methods:In 16 centers, 137 pts with PF-JIA in CID on anti-TNF therapy were enrolled and followed for at least 14 months (mos). During the first 6 study mos pts were maintained on anti-TNF therapy and if CID was maintained, then anti-TNF therapy was stopped. Background medications were stable. S100A12 levels were obtained at the time of anti-TNF withdrawal. The primary outcome was disease “flare” defined by worsening of ≥30% in ≥ 3 of the 6 core set variables, with no more than 1 improving by ≥30%. Parameters had to increase by at least the following amounts: MD and parent globals by 2 units, active and limited joints by 2, CHAQ by 0.125 and ESR from normal to abnormal.Results:24 pts failed to maintain CID in the first 6 study mos and 7 pts were discontinued from the study for other reasons. 106 pts were available for this analysis of whom 39 (37%) experienced flare. The S100A12 levels at time of anti-TNF withdrawal did not differ significantly in regards to JIA type, presence of ANA, MTX co-therapy, or type of anti-TNF therapy and did not correlate with previous duration of CID. Globally, S100A12 at the time of withdrawal did not differ significantly according to disease flare (flare 73 +/− 117 ng/ml, no flare 80 +/− 220 ng/ml) (median ++/− standard deviation). Receiver-operating curve (ROC) analysis computing S100A12 at time of anti-TNF withdrawal against flare for the entire study period demonstrated an area-under-the-curve (AUC) of 0.51, 95% confidence interval (CI) 0.39–0.62, for prediction of flare within 60 days AUC 0.66, 95% CI 0.56–0.75, for prediction of flare within 90 days AUC 0.64, 95% CI 0.54–0.74 and for prediction of flare within 120 days AUC 0.54, 95% CI 0.44–0.64. The S100A12 level at time of withdrawal correlated inversely with the time to flare (Spearman rank correlation = −0.34, p = 0.05). Flares occurred earlier in pts with predefined high (>120 ng/ml) vs. low (≤120 ng/ml). S100A12 levels at time of withdrawal among pts who flared (median time to flare 36 vs. 114 days, p = 0.02). The overall flare rate in patients with high vs. low S100A12 levels at time of withdrawal was 35% vs. 38%, respectively. Kaplan-Meier analysis of disease flare in pts with high vs. low S100A12 levels at time of withdrawal also demonstrated a trend towards earlier disease flare in pts with high S100A12 levels (log rank test significance 0.07).Conclusion:In this prospective study, a substantial proportion of pts with PF-JIA experienced disease flare after anti-TNF withdrawal. Serum S100A12 levels at time of anti-TNF withdrawal did not differ between pts subsequently experiencing disease flare and those not experiencing flare throughout the entire study period. However, pts with high S100A12 levels (>120 ng/ml) experienced earlier disease flare.
    Arthritis & Rheumatology. 03/2014; 66(S11).
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    ABSTRACT: The purpose of our study is to assess practices of North American pediatric rheumatologists regarding monitoring, prevention, and treatment of low bone mineral density (BMD) in children on long-term glucocorticoid treatment. Long-term glucocorticoid therapy is associated with accelerated bone loss. Children with JIA and lupus have low baseline BMD and incident vertebral fractures commonly occur in these groups of patients even after a relatively short period of time being on systemic glucocorticoids. There are no established guidelines for identification, prevention, and treatment of glucocorticoid-induced bone loss in children.
    Pediatric rheumatology online journal. 01/2014; 12:24.
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    ABSTRACT: This study aimed to assess long-term safety and developmental data on juvenile idiopathic arthritis (JIA) patients treated in routine clinical practice with celecoxib or nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs).
    Pediatric rheumatology online journal. 01/2014; 12:29.
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    ABSTRACT: Objective: There is no standardized approach to the initial treatment of polyarticular juvenile idiopathic arthritis (pJIA) among pediatric rheumatologists. Understanding the comparative effectiveness of the diverse therapeutic options available will result in better health outcomes for pJIA. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed consensus treatment plans (CTP) for use in clinical practice to facilitate such studies. Methods: A case-based survey was administered to CARRA members to identify the common treatment approaches for new-onset pJIA. Two face-to-face consensus conferences employed modified nominal group technique to identify treatment strategies, operational case definition, endpoints and data elements to be collected. A core workgroup reviewed the relevant literature, refined plans and developed medication dosing and monitoring recommendations. Results: The initial case-based survey identified significant variability among treatment approaches for new onset pJIA. We developed 3 CTPs based on treatment strategies, for the first 12 months of therapy, as well as case definitions and clinical and laboratory monitoring schedules. The CTPs include a Step-Up Plan (non-biologic DMARD followed by a biologic DMARD), Early Combination Plan (non-biologic and biologic DMARD combined within a month of treatment initiation), and a Biologic Only Plan. This approach was approved by 96% of the CARRA JIA Research Committee members attending the 2013 CARRA face-to-face meeting. Conclusion: Three standardized CTPs were developed for new-onset pJIA. Coupled with data collection at defined intervals, use of these CTPs will enable the study of their comparative effectiveness in an observational setting to optimize initial management of pJIA. © 2013 American College of Rheumatology.
    Arthritis Care & Research. 12/2013;
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    ABSTRACT: Women with SLE have higher rates of persistent human papilloma virus (HPV) infections and precancerous lesions than healthy women. HPV vaccine is safe and effective in healthy females aged 9--26 years. There are limited data on the safety and immunogenicity of HPV vaccine in females with SLE, and none in adolescents with SLE. Our study evaluates the safety and immunogenicity of recombinant quadrivalent HPV vaccine, Gardasil, in adolescents and young women with SLE. This is a prospective, open-label study. Exclusion criteria included disease exacerbation within past 30 days; rituximab or cyclophosphamide within 6 months; pregnancy. Vaccine was administered at months 0, 2, and 6. Physical examination, SLEDAI scores and laboratory studies were performed at months 0, 2, 4, 6 and 7. Each patient's SLEDAI scores and laboratory profile in the year prior to vaccine administration were used as controls for that patient. Primary outcome measures were change in SLEDAI and mean HPV antibody titers. 27 patients, 12 to 26 years, were enrolled; 20 completed the study. Nine had mild/moderate lupus flares. Mean SLEDAI scores decreased from 6.14 pre-vaccination to 4.49 post-vaccination (p = 0.01). Of 12 patients with lupus nephritis, two experienced worsening renal function during/after the study and progressed to renal failure within 18 months of the study. Both had Class IV lupus nephritis with high chronicity scores (>= 8) on renal biopsies performed within one year prior to study entry. Seropositivity post-vaccine was >94% for HPV 6, 11, 16 and 18. Quadrivalent HPV vaccine seems generally safe and well tolerated in this series of adolescents and young women with SLE, with no increase in mean SLEDAI scores. Progression to renal failure in two patients was most likely secondary to pre-existing severe renal chronicity and not secondary to HPV vaccination. Immunogenicity to the quadrivalent HPV vaccine was excellent, with the seropositivity rate >94% in all four HPV types.
    Pediatric Rheumatology 08/2013; 11(1):29. · 1.47 Impact Factor
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    ABSTRACT: Objective: To determine long-term safety and efficacy of rilonacept, an anti-IL-1 fusion protein, in patients with active systemic juvenile idiopathic arthritis (sJIA). Methods: Efficacy was evaluated using adapted ACR Pediatric 30, 50, and 70 criteria in patients, aged 4-20 years, during 23 months of open-label treatment (3 phases) after a 4-week, double-blind, placebo-controlled phase. Following double-blind treatment with 2.2 mg/kg or 4.4 mg/kg of rilonacept, patients were eligible to receive open-label treatment at their prior dose with adjustments. Reduction in prednisone and improvements in laboratory parameters of disease activity (d-dimer and myeloid-related proteins [MRP]) were also evaluated. Results: Twenty-four patients entered the double-blind study and 23 entered the open-label period. Patients were predominantly white, female, and had a median age of 14.0 years at baseline. No significant differences in efficacy were observed between rilonacept and placebo during the double-blind phase, but fever and rash completely resolved by month 3 in all patients during the open-label treatment period and did not recur. Adapted ACR Pediatric 30, 50, and 70 response rates at 3 months from start of study were 78.3%, 60.9%, and 34.8%, respectively; response was generally maintained over the study duration. D-dimer and MRP8/14 levels dramatically improved and prednisone was decreased or discontinued in 22/23 patients. No serious treatment-related adverse events were observed. Conclusions: Sustained improvements in clinical and laboratory assessments of articular and systemic manifestations of sJIA were achieved in >50% of rilonacept-treated patients over 2 years. Treatment with rilonacept had a substantial steroid-sparing effect and was generally well-tolerated © 2013 American College of Rheumatology.
    Arthritis & Rheumatology 06/2013; · 7.48 Impact Factor
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    ABSTRACT: OBJECTIVES: Systemic Juvenile Idiopathic Arthritis (sJIA) is characterized by fevers, rash and arthritis, for which IL1 and IL6 inhibitors appear effective. Pulmonary artery hypertension (PAH), interstitial lung disease (ILD) and alveolar proteinosis (AP) have been recently reported in sJIA patients with increased frequency. Our aim was to characterize and compare these cases to a larger cohort of sJIA patients. METHODS: sJIA patients who developed PAH, ILD and/or AP were identified through an electronic listserv, and their demographic, sJIA and pulmonary disease characteristics, and medication exposure information were collected. These features were compared to a cohort of sJIA patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. RESULTS: Patients (N=25) were significantly (p<0.05) more likely than the CARRA registry cohort (N=389) to be female, have more systemic features, and to have been exposed to an IL-1 inhibitor, tocilizumab, infliximab, corticosteroids, intravenous immunoglobulin, cyclosporine and cyclophosphamide. Eighty% were diagnosed after 2004. Twenty (80%) patients had MAS during their disease course and 15 (60%) had MAS at pulmonary diagnosis. Sixteen patients had PAH, 5 AP and 7 ILD. Seventeen (68%) patients were taking or recently (<1 month) discontinued a biologic agent at pulmonary symptom onset; 12 (48%) were taking anti-IL1 therapy (primarily anakinra). Seventeen (68%) patients died at a mean of 8.8 months from pulmonary diagnosis. CONCLUSIONS: PAH, AP and ILD are under-recognized complications of sJIA which are frequently fatal. These may be the result of severe uncontrolled systemic disease activity, and may be influenced by medication exposure. © 2012 by the American College of Rheumatology.
    Arthritis Care Res (Hoboken). 05/2013; 65(5):745-752.
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    ABSTRACT: OBJECTIVES: This study tested the concurrent validity of the systemic lupus erythematosus responder index (SRI) in assessing improvement in juvenile-onset systemic lupus erythematosus (jSLE). METHODS: The SRI considers changes in the SELENA-SLEDAI, BILAG and a 3-cm visual analogue scale of physician-rated disease activity (PGA) to determine patient improvement. Using prospectively collected data from 760 unique follow-up visit intervals of 274 jSLE patients, we assessed the sensitivity and specificity of the SRI using these external standards: physician-rated improvement (MD-change), patient/parent-rated major improvement of wellbeing (patient-change) and decrease in prescribed systemic corticosteroids (steroid-change). Modifications of the SRI that considered different thresholds for the SELENA-SLEDAI, BILAG and 10-cm PGA were explored and agreement with the American College of Rheumatology/PRINTO provisional criteria for improvement of jSLE (PCI) was examined. RESULTS: The sensitivity/specificity in capturing major improvement by the MD-change were 78%/76% for the SRI and 83%/78% for the PCI, respectively. There was fair agreement between the SRI and PCI (kappa=0.35, 95% CI 0.02 to 0.73) in capturing major improvement by the MD-change. Select modified versions of the SRI had improved accuracy overall. All improvement criteria tested had lower sensitivity when considering patient-change and steroid-change as external standards compared to MD-change. CONCLUSIONS: The SRI and its modified versions based on meaningful changes in jSLE have high specificity but at most modest sensitivity for capturing jSLE improvement. When used as an endpoint of clinical trials in jSLE, the SRI will provide a conservative estimate regarding the efficacy of the therapeutic agent under investigation.
    Annals of the rheumatic diseases 01/2013; · 8.11 Impact Factor
  • Source
    Pediatric Rheumatology 07/2012; 10(1). · 1.47 Impact Factor
  • Source
    Pediatric Rheumatology 07/2012; 10(1). · 1.47 Impact Factor
  • Source
    Karen B Onel, Kenan Onel
    Arthritis & Rheumatology 02/2012; 64(4):966-9. · 7.48 Impact Factor

Publication Stats

502 Citations
106.54 Total Impact Points

Institutions

  • 2010–2014
    • University of Illinois at Chicago
      Chicago, Illinois, United States
  • 2009–2014
    • University of Chicago
      • Department of Pediatrics
      Chicago, Illinois, United States
  • 2008–2014
    • The University of Chicago Medical Center
      • Section of Rheumatology (Pediatrics)
      Chicago, Illinois, United States
  • 2010–2013
    • University of Cincinnati
      • Department of Sciences & Health
      Cincinnati, Ohio, United States
  • 2008–2012
    • Cincinnati Children's Hospital Medical Center
      • • Division of Rheumatology
      • • Department of Pediatrics
      • • Division of Nephrology and Hypertension
      Cincinnati, OH, United States
  • 2000–2005
    • Cornell University
      • Department of Pediatrics
      Ithaca, NY, United States
  • 1995–2005
    • Hospital for Special Surgery
      • Department of Pediatrics
      New York City, New York, United States