54 research outputs found
Comparison of treatment response, remission rate and drug adherence in polyarticular juvenile idiopathic arthritis patients treated with etanercept, adalimumab or tocilizumab
Background Treatment response, remission rates and compliance in patients with
polyarticular juvenile idiopathic arthritis (polyJIA) treated with adalimumab,
etanercept, or tocilizumab were analyzed in clinical practice. Methods Data
collected in the German BIKER registry were analyzed in patients with polyJIA
who started treatment with approved biologics, adalimumab, etanercept or
tocilizumab, from 2011 to 2015. Baseline patient characteristics, treatment
response, safety and drug survival were compared. Results Two hundred thirty-
six patient started adalimumab, 419 etanercept and 74 tocilizumab, with
differences in baseline patient characteristics. Baseline Juvenile Disease
Activity Score (JADAS)10 (mean ± SD) in the adalimumab/etanercept/tocilizumab
cohorts was 12.1+/â7.6, 13.8 ± 7.1 and 15.1 ± 7.4, respectively (adalimumab vs
etanercept, pâ=â0.01), and Childhood Health Assessment Questionnaire
(CHAQ)-disability index scores was 0.43 ± 0.58, 0.59 ± 0.6 and 0.63 ± 0.55,
respectively (adalimumab vs etanercept, pâ<â0.001). Uveitis history was more
frequent in the adalimumab cohort (OR 5.73; pâ<â0.001). Balanced patientsâ
samples were obtained by a generalized propensity score to adjust for baseline
differences. Pediatric ACR30/50/70/90 criterion improvement after 3 months
treatment was achieved by 68%/60%/42%/24% in the etanercept cohort,
67%/59%/43%/27% in the adalimumab cohort and 61%/52%/35%/26% in the
tocilizumab cohort. At 24 months, JADAS minimal disease activity was achieved
in 52.4%/61.3%/52.4% and JADAS remission in 27.9%/34.8%/27.9% patients in the
adalimumab/etanercept/tocilizumab cohorts, respectively. Etanercept was used
in 95.5% of patients as a first biologic, adalimumab in 50.8% and tocilizumab
in 20.2%. There were no important differences in efficacy between first-line
and second-line use of biologics. In total 60.4%/49.4%/31.1% patients
discontinued adalimumab/etanercept/tocilizumab, respectively (HR for
adalimumab 1.67; pâ<â0.001; HR for tocilizumab 0.35; pâ=â0.001). Drug survival
rates did not differ significantly in patients on biologic monotherapy
compared with combination therapy with methotrexate. Over 4 years observation
under etanercept/adalimumab/tocilizumab, 996/386/103 adverse events, and
148/119/26 serious adverse events, respectively, were reported. Conclusions In
clinical practice, etanercept is most frequently used as first-line biologic.
Adalimumab/etanercept/tocilizumab showed comparable efficacy toward polyJIA.
Overall, tolerance was acceptable. Interestingly, compliance was highest with
tocilizumab and lowest with adalimumab. This study provides the first
indication for the comparison of different biologic agents in polyarticular
JIA based on observational study data with all their weaknesses and
demonstrates the need for well-controlled head-to-head studies for
confirmation
Rotavirus Disease in Germany-A Prospective Survey of Very Severe Cases
Objective: Rotavirus (RV) gastroenteritis is a notifiable disease in Germany. The reports to the authorities contain few data concerning the severity of disease. The aims of this study were to determine incidence and outcome of very severe cases of RV disease. Methods: Cases of very severe RV disease were collected by the German Paediatric Surveillance Unit for rare diseases (Erhebungseinheit fur seltene padiatrische Erkrankungen in Deutschland) using anonymous questionnaires based on hospitalized patients between April 2009 and March 2011. Inclusion criteria were detection of RV antigen in feces, patient aged 0-16 years and 1 or more of the following criteria: intensive care treatment, hypernatremia or hyponatremia (> 155 mmol/ L or < 125 mmol/ L), clinical signs of encephalopathy (somnolence, seizures, apnea) and RV-associated death. Results: During 2 years, 130 cases of very severe RV disease were reported, 101 of 130 were verified. Seventeen patients had nosocomial infection, of whom 14 were neonates in intensive care. Among those, 12 infants had verified or suspected necrotizing enterocolitis. Eighty-four community-acquired cases were reported, median age was 10.5 months (0-108 months). The median hospital stay was 6 days, and 48 patients needed intensive care treatment. Among children less than 5 years of age, the yearly incidence of community-acquired very severe RV disease was 1.2 of 100,000 (95% confidence interval: 0.9-1.4/100,000). A total of 26 of 84 and 10 of 84 patients had severe hypernatremia or hyponatremia, respectively, and 58 of 84 patients had signs of encephalopathy. Three deaths were reported (1 nosocomial and 2 community acquired). Conclusions: RV infection in Germany can have a life-threatening course. A substantial number are nosocomial infections
Rotavirus Disease in Germany-A Prospective Survey of Very Severe Cases
Objective: Rotavirus (RV) gastroenteritis is a notifiable disease in Germany. The reports to the authorities contain few data concerning the severity of disease. The aims of this study were to determine incidence and outcome of very severe cases of RV disease. Methods: Cases of very severe RV disease were collected by the German Paediatric Surveillance Unit for rare diseases (Erhebungseinheit fur seltene padiatrische Erkrankungen in Deutschland) using anonymous questionnaires based on hospitalized patients between April 2009 and March 2011. Inclusion criteria were detection of RV antigen in feces, patient aged 0-16 years and 1 or more of the following criteria: intensive care treatment, hypernatremia or hyponatremia (> 155 mmol/ L or < 125 mmol/ L), clinical signs of encephalopathy (somnolence, seizures, apnea) and RV-associated death. Results: During 2 years, 130 cases of very severe RV disease were reported, 101 of 130 were verified. Seventeen patients had nosocomial infection, of whom 14 were neonates in intensive care. Among those, 12 infants had verified or suspected necrotizing enterocolitis. Eighty-four community-acquired cases were reported, median age was 10.5 months (0-108 months). The median hospital stay was 6 days, and 48 patients needed intensive care treatment. Among children less than 5 years of age, the yearly incidence of community-acquired very severe RV disease was 1.2 of 100,000 (95% confidence interval: 0.9-1.4/100,000). A total of 26 of 84 and 10 of 84 patients had severe hypernatremia or hyponatremia, respectively, and 58 of 84 patients had signs of encephalopathy. Three deaths were reported (1 nosocomial and 2 community acquired). Conclusions: RV infection in Germany can have a life-threatening course. A substantial number are nosocomial infections
Progress in pediatric rheumatology: apprehend the opportunities of the future without forgetting the lessons from the past
The German version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR)
The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the German language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. The participating centres were asked to collect demographic and clinical data along the JAMAR questionnaire in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling effects, internal consistency, Cronbach\u2019s alpha, interscale correlations, test\u2013retest reliability, and construct validity (convergent and discriminant validity). A total of 319 JIA patients (2.8% systemic, 36.7% oligoarticular, 23.5% RF negative polyarthritis, and 37% other categories) and 100 healthy children were enrolled in eight centres. The JAMAR components discriminated well healthy subjects from JIA patients. All JAMAR components revealed good psychometric performances. In conclusion, the German version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and in clinical research
Post-Pandemic Seroprevalence of Pandemic Influenza A (H1N1) 2009 Infection (Swine Flu) among Children <18 Years in Germany
We determined antibodies to the pandemic influenza A (H1N1) 2009 virus in children to assess: the incidence of (H1N1) 2009 infections in the 2009/2010 season in Germany, the proportion of subclinical infections and to compare titers in vaccinated and infected children. Eight pediatric hospitals distributed over Germany prospectively provided sera from in- or outpatients aged 1 to 17 years from April 1(st) to July 31(st) 2010. Vaccination history, recall of infections and sociodemographic factors were ascertained. Antibody titers were measured with a sensitive and specific in-house hemagglutination inhibition test (HIT) and compared to age-matched sera collected during 6 months before the onset of the pandemic in Germany. We analyzed 1420 post-pandemic and 300 pre-pandemic sera. Among unvaccinated children aged 1-4 and 5-17 years the prevalence of HI titers (â„1â¶10) was 27.1% (95% CI: 23.5-31.3) and 53.5% (95% CI: 50.9-56.2) compared to 1.7% and 5.5%, respectively, for pre-pandemic sera, accounting for a serologically determined incidence of influenza A (H1N1) 2009 during the season 2009/2010 of 25,4% (95% CI : 19.3-30.5) in children aged 1-4 years and 48.0% (95% CI: 42.6-52.0) in 5-17 year old children. Of children with HI titers â„1â¶10, 25.5% (95% CI: 22.5-28.8) reported no history of any infectious disease since June 2009. Among vaccinated children, 92% (95%-CI: 87.0-96.6) of the 5-17 year old but only 47.8% (95%-CI: 33.5-66.5) of the 1-4 year old children exhibited HI titers against influenza A virus (H1N1) 2009. Serologically determined incidence of influenza A (H1N1) 2009 infections in children indicates high infection rates with older children (5-17 years) infected twice as often as younger children. In about a quarter of the children with HI titers after the season 2009/2010 subclinical infections must be assumed. Low HI titers in young children after vaccination with the AS03(B)-adjuvanted split virion vaccine need further scrutiny
Longâterm safety, efficacy, and quality of life in patients with juvenile idiopathic arthritis treated with intravenous abatacept for up to seven years
ClinicalTrials.gov identifier: NCT00095173[Abstract] Objective. The efficacy and safety of abatacept in patients with juvenile idiopathic arthritis (JIA) who experienced an inadequate response to diseaseâmodifying antirheumatic drugs were previously established in a phase III study that included a 4âmonth openâlabel leadâin period, a 6âmonth doubleâblind withdrawal period, and a longâterm extension (LTE) phase. The aim of this study was to present the safety, efficacy, and patientâreported outcomes of abatacept treatment (10 mg/kg every 4 weeks) during the LTE phase, for up to 7 years of followup.
Methods. Patients enrolled in the phase III trial could enter the openâlabel LTE phase if they had not achieved a response to treatment at month 4 or if they had received abatacept or placebo during the doubleâblind period.
Results. One hundred fiftyâthree (80.5%) of 190 patients entered the LTE phase, and 69 patients (36.3%) completed it. The overall incidence rate (events per 100 patientâyears) of adverse events decreased during the LTE phase (433.61 events during the shortâterm phase [combined leadâin and doubleâblind periods] versus 132.39 events during the LTE phase). Similar results were observed for serious adverse events (6.82 versus 5.60), serious infections (1.13 versus 1.72), malignancies (1.12 versus 0), and autoimmune events (2.26 versus 1.18). American College of Rheumatology (ACR) Pediatric 30 (Pedi 30) responses, Pedi 70 responses, and clinically inactive disease status were maintained throughout the LTE phase in patients who continued to receive therapy. Improvements in the Child Health Questionnaire physical and psychosocial summary scores were maintained over time.
Conclusion. Longâterm abatacept treatment for up to 7 years was associated with consistent safety, sustained efficacy, and qualityâofâlife benefits in patients with JIA
Intravenous dosing of tocilizumab in patients younger than two years of age with systemic juvenile idiopathic arthritis
The anti-interleukin-6 receptor-alpha antibody tocilizumab was approved for intravenous (IV) injection in the treatment of patients with systemic juvenile idiopathic arthritis (sJIA) aged 2 to 17 years based on results of a randomized controlled phase 3 trial. Tocilizumab treatment in systemic juvenile idiopathic arthritis (sJIA) patients younger than 2 was investigated in this open-label phase 1 trial and compared with data from the previous trial in patients aged 2 to 17 years.Patients younger than 2 received open-label tocilizumab 12 mg/kg IV every 2 weeks (Q2W) during a 12-week main evaluation period and an optional extension period. The primary end point was comparability of pharmacokinetics during the main evaluation period to that of the previous trial (in patients aged 2-17 years), and the secondary end point was safety; pharmacodynamics and efficacy end points were exploratory. Descriptive comparisons for pharmacokinetics, pharmacodynamics, safety, and efficacy were made with sJIA patients aged 2 to 17 years weighing < 30 kg (n = 38) who received tocilizumab 12 mg/kg IV Q2W in the previous trial (control group).Eleven patients (mean age, 1.3 years) received tocilizumab during the main evaluation period. The primary end point was met: tocilizumab exposures for patients younger than 2 were within the range of the control group (mean [±SD] Όg/mL concentration at the end-of-dosing interval [Cmin]: 39.8 [±14.3] vs 57.5 [±23.3]; maximum concentration [Cmax] postdose: 288 [±40.4] vs 245 [±57.2]). At week 12, pharmacodynamic measures were similar between patients younger than 2 and the control group; mean change from baseline in Juvenile Arthritis Disease Activity Score-71 was - 17.4 in patients younger than 2 and - 28.8 in the control group; rash was reported by 14.3 and 13.5% of patients, respectively. Safety was comparable except for the incidence of serious hypersensitivity reactions (27.3% in patients younger than 2 vs 2.6% in the control group).Tocilizumab 12 mg/kg IV Q2W provided pharmacokinetics, pharmacodynamics, and efficacy in sJIA patients younger than 2 comparable to those in patients aged 2 to 17 years. Safety was comparable except for a higher incidence of serious hypersensitivity events in patients younger than 2 years.Juvenile idiopathic arthritis.ClinicalTrials.gov, NCT01455701 . Registered, October 20, 2011, Date of enrollment of first participant: October 26, 2012
Efficacy and safety of pharmacological treatments for Lyme neuroborreliosis in children: a systematic review
Practice and consensus-based strategies in diagnosing and managing systemic juvenile idiopathic arthritis in Germany
Background: Systemic juvenile idiopathic arthritis (SJIA) is an autoinflammatory disease associated with chronic arthritis. Early diagnosis and effective therapy of SJIA is desirable, so that complications are avoided. The PRO-KIND initiative of the German Society for Pediatric Rheumatology (GKJR) aims to define consensus-based strategies to harmonize diagnostic and therapeutic approaches in Germany. Methods: We analyzed data on patients diagnosed with SJIA from 3 national registries in Germany. Subsequently, via online surveys and teleconferences among pediatric rheumatologists with a special expertise in the treatment of SJIA, we identified current diagnostic and treatment approaches in Germany. Those were harmonized via the formulation of statements and, supported by findings from a literature search. Finally, an in-person consensus conference using nominal group technique was held to further modify and consent the statements. Results: Up to 50% of patients diagnosed with SJIA in Germany do not fulfill the International League of Associations for Rheumatology (ILAR) classification criteria, mostly due to the absence of chronic arthritis. Our findings suggest that chronic arthritis is not obligatory for the diagnosis and treatment of SJIA, allowing a diagnosis of probable SJIA Malignant, infectious and hereditary autoinflammatory diseases should be considered before rendering a diagnosis of probable SJIA There is substantial variability in the initial treatment of SJIA. Based on registry data, most patients initially receive systemic glucocorticoids, however, increasingly substituted or accompanied by biological agents, i.e. interleukin (IL)-1 and IL-6 blockade (up to 27.2% of patients). We identified preferred initial therapies for probable and definitive SJIA, including step-up patterns and treatment targets for the short-term (resolution of fever, decrease in C-reactive protein by 50% within 7 days), the mid-term (improvement in physician global and active joint count by at least 50% or a JADAS-10 score of maximally 5.4 within 4 weeks) and the long-term (glucocorticoid-free clinically inactive disease within 6 to 12 months), and an explicit treat-to-target strategy. Conclusions: We developed consensus-based strategies regarding the diagnosis and treatment of probable or definitive SJIA in Germany
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