Update of evidence- and consensus-based guidelines for the treatment of juvenile idiopathic arthritis (JIA) by the German Society of Pediatric and Juvenile Rheumatic Diseases (GKJR): New perspectives on interdisciplinary care.

BACKGROUND: New therapeutic strategies for juvenile idiopathic arthritis (JIA) have evolved within the past ten years, and as a result, an update of the 2011 recommendations of the German management guidelines was initiated. METHODS: A systemic literature review was performed, overarching principles were proposed and pre-selected via an online survey followed by two multidisciplinary consensus conferences. Pharmacological and non-pharmacological treatments were discussed, statements were proposed and ultimately agreed upon by nominal group technique (NGT). RESULTS: 12 overarching therapeutic principles, as well as 9 recommendations on pharmacological and 5 on non-pharmacological treatments for JIA were agreed upon. CONCLUSION: This report summarizes the recent update of the interdisciplinary, consensus-based German guidelines on the management of JIA. The multi- and interdisciplinary participation of all caregivers was central for this patient-focused update. With these guidelines, physicians can choose an evidence-based approach, which allows better tailored treatment in this vulnerable cohort of children and adolescents.

Comparing clinical characteristics of pediatric patients with pancreatic diabetes to patients with type 1 diabetes: A matched case-control study.

BACKGROUND: Only few studies have been conducted on pancreatic diabetes and data from large epidemiological studies are missing. Our main objective was to study the most important differences and similarities between pediatric individuals with pancreatic diabetes and type 1 diabetes (T1D). METHODS: Patients <20 years of age were identified from the diabetes patient follow-up registry (DPV). Data of the most recent treatment year between January 2000 and March 2018 were aggregated. Propensity score was used to match individuals with pancreatic diabetes to individuals with T1D. Matching was conducted one-to-one by sex, age, diabetes duration, body mass index SD score (BMI-SDS), and migration background. RESULTS: We studied 731 individuals with pancreatic diabetes and 74 460 with T1D. In the matched cohort of 631 pairs, HbA1c was significantly lower in pancreatic diabetes (7.4% [95% confidence interval: 7.2; 7.5%]) compared to T1D patients (8.7% [8.5; 8.8%]). Daily insulin dose (0.80 IU/kg [0.77; 0.84] vs 0.86 IU/kg [0.82; 0.90]) and insulin pump use (13.3% [10.7; 16.4] vs 22.1% [19.0; 25.6%]) were lower in patients with pancreatic diabetes. However, event rates of severe hypoglycemia were similar between pancreatic and T1D patients (8.8 [5.4; 14.2] vs 9.6 [5.9; 15.6] events per 100 patient years). CONCLUSIONS: With the use of robust epidemiological data, our study improves the knowledge on clinical characteristics in pediatric individuals with pancreatic diabetes. Moreover, our results serve as a basis to reconsider treatment options and for discussing clinical practice guidelines for patients with this rare medical condition.

Comorbidity of Type 1 Diabetes Mellitus in Patients with Juvenile Idiopathic Arthritis.

OBJECTIVES: To determine the prevalence of type 1 diabetes mellitus (T1D) in patients with juvenile idiopathic arthritis (JIA) and to characterize patients having both. STUDY DESIGN: Diabetes comorbidity was recorded in the National Pediatric Rheumatologic Database since 2012. Data from the North Rhine-Westphalian diabetes registry served as the reference population for the prevalence of diabetes in the general population. The National Pediatric Rheumatologic Database data were indirectly standardized for age and sex for comparison with the general population. The diabetes prevalence ratio was calculated using the Poisson regression model. RESULTS: The analysis included 12 269 patients with JIA. A total of 58 patients had comorbid T1D, and the diabetes prevalence was 0.5%. The mean age was 11.6 years at the time of documentation, and the mean disease duration was 4.2 years. Compared with the general population, the prevalence of diabetes in patients with JIA was significantly increased (prevalence ratio 1.76 [95% CI 1.34; 2.28], P < .001). The onset of diabetes in patients with JIA was earlier than that reported in the reference data. Sixty-three percent of patients developed T1D before JIA. On average, diabetes onset was 56 months before the onset of JIA. Patients who first developed JIA developed T1D on average 40 months later. The majority of patients had not received disease-modifying antirheumatic drugs before diabetes onset. CONCLUSIONS: T1D occurs more frequently in patients with JIA than in the general population. The likelihood of T1D occurrence appears to be slightly higher before JIA manifestation and without disease-modifying antirheumatic drug therapy after JIA onset.

Diabetes mellitus in pediatric solid organ recipients without and with cystic fibrosis: An analysis from the German-Austrian diabetes database (Diabetes Patienten Verlaufsdokumentation).

INTRODUCTION: Posttransplantation diabetes mellitus (PTDM) increases the risk of cardiovascular disease, graft loss, and decreased survival. Follow-up treatment after solid organ transplantation (SOT) needs to focus on, inter alia, maintaining balanced glucose metabolism. This study aimed to ascertain the prevalence of PTDM and describe patient characteristics in the large DPV (Diabetes Patienten Verlaufsdokumentation) pediatric diabetes database. METHODS: DPV data of 71 902 patients from the January 01, 1995 to January 04, 2015 period were analyzed for patients with and without cystic fibrosis (CF) after SOT (kidney, liver, heart, and lung). Multivariable analysis served to assess differences between SOT patient groups at risk for developing diabetes. RESULTS: Out of 109 SOT patients, 51 had CF; 72.5% received steroids and 62% were additionally given tacrolimus. PTDM developed in 45% of CF patients and 12% of non-CF patients. SOT patients were older at diabetes onset (mean age, 12.50 ± 3.98 years), shorter (height z-score, -1.67 ± 1.25), and lighter (weight z-score, -1.59 ± 1.57) than non-SOT diabetes patients (P < 0.01). With transplantation, glycated hemoglobin (HbA1c) was significantly lower and treatment for hypertension and dyslipidemia was increased. Among SOT patients, weight and body mass index (BMI) z-scores were significantly lower in patients with CF-related diabetes (P < 0.05). CONCLUSIONS: SOT was present in 6.6% of children with diabetes, and this might aggravate the risk of cardiovascular disease in populations with already increased rates of hypertension and dyslipidemia. Dystrophy and short stature were also present, particularly in transplant recipients with CF and diabetes. Comorbidities and long-term consequences call for multidisciplinary collaboration.

Low prevalence of patients with mitochondrial disease in the German/Austrian DPV diabetes registry.

UNLABELLED: The aim of this study was to characterize the phenotype and treatment of young patients (manifestation <30 years) with diabetes of mitochondrial origin (DMO), based on the German/Austrian DPV (Diabetes Patienten Verlaufsdokumentation) registry. Only 13 (0.02 %) of all patients with diabetes in this cohort were identified with DMO, mainly due to the Kearns-Sayre (n = 5), Pearson (n = 3), or mitochondrial myopathy, encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome (n = 2). The onset of DMO (14.2, interquartile range (IQR) 7.1-16 years) was later than diabetes onset in individuals with T1D but earlier than in T2D. At manifestation, patients exhibited a mild elevation of blood glucose concentrations (251, IQR 178-299 mg/dl) without ketoacidosis. They had lower body mass index (BMI) values (-1.39 ± 0.28 kg/m(2)) than peers with T1D or T2D (p < 0.0001) and higher triglycerides (211, IQR 134-574 mg/dl) than in T1D (p = 0.04) while there was a high rate of dyslipidemia (86 %). Insulin requirements (0.58, IQR 0.37-0.90 U/kg/d) were between T1D and T2D while glucometabolic control (glycated hemoglobin A1c (HbA1c) 7.4 ± 0.52 %) in DMO was comparable to age-matched T2D and stable over a 5-year follow-up. CONCLUSION: Primary mitochondrial disorders are a rare cause of juvenile diabetes and likely to be underdiagnosed. As there is clinical overlap with T1D and T2D, dyslipidemia and low body weight may help to identify further DMO cases. WHAT IS KNOWN: • In adults diabetes of mitochondrial origin (DMO) is a rare cause of non-autoimmune diabetes, affecting about 0.8 % of diabetes cases. • Common features are a maternal family history of diabetes, hearing loss and neurological abnormalities. What is New: • In our juvenile cohort 0.02 % of diabetes patients (age < 30 years) were affected by DMO, while Kearns Sayre, MELAS and Pearson syndrome were the most frequent entities. • Juvenile DMO patients exhibited dyslipidemia, higher triglycerides and a lower BMI than peers with T1D or T2D, while some patients also showed retinal changes.

Comorbidity of type 1 diabetes and juvenile idiopathic arthritis.

OBJECTIVE: To analyze the prevalence of juvenile idiopathic arthritis (JIA) and diabetes end points in pediatric patients with type 1 diabetes. STUDY DESIGN: Patients with type 1 diabetes, recorded from 1995 up to September 2013 in the Diabetes Patienten Verlaufsdokumentation database (n = 54,911, <16 years of age, 47% girls), were analyzed. The patients' height, weight, and body mass index SDS, glycosylated hemoglobin A1c (HbA1c); insulin dose; hypertension and dyslipidemia prevalence; rate of hypoglycemic events; and ketoacidosis were compared between patients with and without JIA. To adjust for age, sex, diabetes duration, and migration background, data were analyzed in hierarchic multivariable regression models. RESULTS: The prevalence of JIA in type 1 diabetes was 106 of 54,911 patients; 66% were girls. Diabetes onset was earlier in children with JIA (7.2 years vs 8.3 years, P = .04). Children with JIA were smaller (SDS: -0.22 vs 0.09, P = .004). Correspondingly, weight SDS was lower in patients with JIA (-0.02 vs 0.22, P = .01). Body mass index SDS did not differ. HbA1c was marginally lower in children with JIA (63 mmol/mol [8.0%] vs 67 mmol/mol [8.3%], P = .06). Insulin requirement was greater in patients with JIA (1.03 vs 0.93 insulin units/weight/day, P = .003). Hypertension and dyslipidemia were comparable in both groups. CONCLUSIONS: The JIA-prevalence in patients with type 1 diabetes (0.19%) was considerably greater than in the general population (0.05%). Growth is influenced negatively by JIA. Surprisingly, HbA1c was somewhat lower in children with JIA, possibly because of a more intensive treatment or a latent hemolysis caused by the inflammation.

Why is insulin pump treatment rarely used in adolescents and young adults with cystic fibrosis-related diabetes?

BACKGROUND: In type 1 diabetes (T1D), the use of continuous subcutaneous insulin infusion (CSII) has increased steadily in the last years. Compared with conventional insulin injection regimes, major advantages might be a nearly physiological insulin secretion, lower rates of hypoglycemia, higher flexibility in daily life, and increased quality of life. Data on CSII in cystic fibrosis-related diabetes (CFRD) are scarce. OBJECTIVE: To analyze current use of insulin pumps in CFRD and compare demographics of pump-treated patients between CFRD and T1D. METHODS: Data from the prospective German/Austrian diabetes patient registry on insulin-treated patients with either CFRD (n = 515) or T1D (n = 43 165) aged >10 yr at manifestation of diabetes were analyzed. RESULTS: A total of 4.1% (n = 21) of CFRD and 17.7% (n = 7647) of T1D patients received insulin pump treatment within the recent year of care (p < 0.001). Pump-treated patients with CFRD had a significantly shorter duration of diabetes [median (Q1 ; Q3 ): 5.8 (2.9; 9.5) vs. 7.8 (4.3; 20.4) yr, p = 0.026] and tended to be younger [22.0 (18.2; 30.1) vs. 24.9 (17.3; 45.9) yr] than pump-treated T1D patients. Age at initiation of CSII seemed to be lower in CFRD [19.2 (16.5; 29.2) vs. 23.3 (14.8; 43.5) yr]. Insulin pump therapy was used slightly more often in male CFRD patients than females (4.7 vs. 3.6%), whereas in T1D the opposite was observed (14.9 vs. 21.2%, p < 0.001). Discontinuation rate of CSII was higher in CFRD than T1D (30.0 vs. 12.7%, p = 0.005). CONCLUSIONS: Despite potential advantages, insulin pump therapy was rarely used among adolescent and young adult CFRD patients.

Cystic fibrosis-related diabetes compared with type 1 and type 2 diabetes in adults.

BACKGROUND: With increasing life expectancy of patients with cystic fibrosis (CF), secondary diabetes becomes more prevalent. It appears to be the most common co-morbidity in persons with cystic fibrosis. Therefore, the objective of our study was to describe characteristics of cystic fibrosis-related diabetes compared with type 1 and 2 diabetes (T1DM/T2DM) in adults. METHODS: Data from 218 436 patients >18 years with cystic fibrosis (n = 401), T1DM (n = 32,409) or T2DM (n = 185 626) in the multicenter Diabetes-Patienten-Verlaufsdokumentation or prospective documentation of diabetes patients registry were analysed. RESULTS: Diabetes onset [median (interquartile range)] in cystic fibrosis [18.70 (15.50-25.30) years] was between T1DM [16.40 (10.50-31.80) years] and T2DM [58.50 (48.80-68.00) years], with female preponderance. Body mass index (BMI) and glycosylated haemoglobin (HbA1c ) were lowest (19.6 [18.1-21.5] kg/m(2) )/50 mmol/mol (6.73%) versus T1DM (24.4 [22.1-27.4])/62 mmol/mol (7.83%) vs. T2DM (29.6 [26.1-33.9])/54 mmol/mol (7.06%); all p < 0.01. A total of 78.6% of cystic fibrosis patients with diabetes received insulin. Insulin dose (0.74 IE/kg bodyweight) was not significantly different from T1DM (0.73) and T2DM (0.76). Frequency of vascular complications, adjusted for confounding effects, across the groups was different: Hypertension (CFRD 16.1% vs. T1DM 24.0% vs. T2DM 32.2%; all p < 0.01), retinopathy (CFRD 10.7% vs. T1DM 10.4% vs. T2DM 10.5%, not significant), nephropathy (CFRD 25.2% vs. T1DM 17.2% vs. T2DM 24.7%; only T1DM/T2DM; p < 0.01). CONCLUSION: CFRD is a uniquely complex entity with clear differences from T1DM and T2DM in adults.

Lung function in children and adolescents with juvenile idiopathic arthritis during long-term treatment with methotrexate: a retrospective study.

OBJECTIVES: Methotrexate may cause severe adverse pulmonary side-effects in adults with rheumatoid arthritis. Our aim was to examine the long-term effect of MTX on lung function in patients with juvenile idiopathic arthritis (JIA). METHODS: We retrospectively reviewed the charts of all 68 patients with JIA treated with MTX at our centre over a 14-year period. Results of annual pulmonary function tests (PFT) were compared using paired t-tests adjusted by Bonferroni correction and by linear regression analysis. RESULTS: The patients in our study had taken MTX for a median of 6.7 years with a median cumulative dose of 3219 mg. In a subgroup of 37 patients PFT had been performed before the onset of MTX. In this subgroup there was a significant decrease of mean mid-expiratory flow (MMEF) after 3 years (-14.0%, p<0.001) of MTX. Diffusion capacity of the lung for carbon monoxide (DLCO) was reduced after the third year (-12.4%, p=0.001). In the total group there was a decrease in MMEF between years 3 and 4 after MTX onset (-13.5%, p=0.001). Forced expiratory volume (FEV1) showed a slight rise between years 4 and 5 (+5.5%, p=0.003). All other parameters remained without significant changes. There was no correlation of PFT results and cumulative MTX dose or JIA subtype. None of our patients developed clinically relevant lung disease. CONCLUSIONS: In summary we found some declines of MMEF and DLCO during long-term treatment with MTX. Overall our data confirm the relative safety of long-term MTX treatment in patients with JIA. We conclude that further data on the development of pulmonary function in patients receiving MTX therapy would be helpful.

Disease impact and disease-unrelated strain in parents of children with rheumatic disease: is there an influence on disease-related information needs?

OBJECTIVE: To explore the information needs of parents of children with juvenile idiopathic arthritis and other rheumatic diseases with emphasis on possible intervening factors, such as disease-related or disease-unrelated strain. METHODS: A cross-sectional, anonymous survey using a purpose-designed questionnaire, incorporating, among others, the Impact on Family Scale. The questionnaire was sent to 146 families continuously attending a pediatric rheumatology outpatient clinic. The response rate was 80%. The mean age of the children was 6.9 (± 4.3) years. Mean CHAQ score was 0.259 (± 0.45; range 0.0 to 2.13). RESULTS: Parents considered themselves well-informed. They frequently mentioned having received information on core domains of medical aspects. They described deficits related to psychosocial impact, to vocational education and to complementary therapy. However, their interest in further information was high, almost irrespective of the amount of prior information. Unexpectedly, neither disease impact on the family nor the presence and number of disease-unrelated life events seemed to have an influence (positive or negative) on the parents' information needs. CONCLUSION: With respect to individually tailored information strategies, it should be taken into account that even for topics largely covered by usual medical advice, residual interest and information needs remain high. We were furthermore able to ascertain topics of particular interest but failed to substantiate our clinical impression that families who feel burdened with disease-related and or disease-unrelated stressors are less likely to be interested in further disease-related information.

Safety and efficacy of once weekly etanercept 0.8 mg/kg in a multicentre 12 week trial in active polyarticular course juvenile idiopathic arthritis.

OBJECTIVES: Etanercept, a recombinant TNF receptor fusion protein, has been approved for the treatment of resistant polyarticular course juvenile idiopathic arthritis at a dosage of 0.4 mg/kg twice weekly in children older than 4 years. In adult patients, efficacy and safety of etanercept 25 mg twice weekly was comparable with 50 mg once weekly. Therefore, safety and efficacy of etanercept once weekly 0.8 mg/kg up to 50 mg s.c. was evaluated in a 3 month open label trial. METHODS: Twenty patients 4 to 17 years old received 0.8 mg of etanercept per kilogram of body weight subcutaneously once weekly for 3 months in an open multicentre trial. Active polyarticular disease was defined by the presence of five or more active joints with swelling, alternatively with pain or tenderness combined with limitation of motion. Safety assessments were based on adverse events (AEs) reports. Efficacy was assessed using the PedACR30/50/70 criteria. RESULTS: At the start of treatment the patients showed high disease activity. A rapid reduction of all disease activity parameters was observed. A PedACR30/50/70 response was reached by 75%/35%/10% of patients after 4 weeks, 90%/75%/35% after 8 weeks and 95%/75%/75% after 12 weeks of treatment. There were 37 AEs, none of them serious, with injection site reactions and minor infections being the most frequent. There was no drop out. Long-term follow-up of the patients will be carried out in the German JIA Registry. CONCLUSION: Treatment with etanercept once weekly using a double dosage leads to a significant improvement of disease activity in patients with active polyarticular course juvenile idiopathic arthritis and is well tolerated.

Vitamin D deficiency is associated with higher disease activity and the risk for uveitis in juvenile idiopathic arthritis - data from a German inception cohort.

OBJECTIVE: The objective was to evaluate the 25(OH) vitamin D (25(OH)D) status of patients with juvenile idiopathic arthritis (JIA) and determine whether the 25(OH)D level is associated with disease activity and the course of JIA. METHODS: Patients ≤ 16 years of age with recently diagnosed JIA (< 12 months) were enrolled in the inception cohort of patients with newly diagnosed JIA (ICON), an ongoing prospective observational, controlled multicenter study started in 2010. Clinical and laboratory parameters were ascertained quarterly during the first year and half-yearly thereafter. Of the 954 enrolled patients, 360 patients with two blood samples taken during the first 2 years after inclusion and with follow up of 3 years were selected. The serum 25(OH)D levels were determined and compared with those of subjects from the general population after matching for age, sex, migration status and the month of blood-drawing. RESULTS: Nearly half of the patients had a deficient 25(OH)D level (< 20 ng/ml) in the first serum sample and a quarter had a deficient level in both samples. Disease activity and the risk of developing JIA-associated uveitis were inversely correlated with the 25(OH)D level (ß = - 0.20, 95% CI - 0.37; 0.03, hazard ratio 0.95, 95% CI 0.91; 0.99, respectively). CONCLUSION: In this study, 25(OH)D deficiency was common and associated with higher disease activity and risk of developing JIA-associated uveitis. Further studies are needed to substantiate these results and determine whether correcting 25(OH)D deficiency is beneficial in JIA.

Outcome and Trends in Treatment of Systemic Juvenile Idiopathic Arthritis in the German National Pediatric Rheumatologic Database, 2000-2013.

OBJECTIVE: To investigate the clinical presentation and medical treatment of patients with systemic juvenile idiopathic arthritis (JIA) during the first year of illness. Our study focused on 3-year outcomes in a subsample of patients who were followed up longitudinally. METHODS: From 2000 to 2013, 597 patients with systemic JIA and a disease duration of ≤12 months were recorded in the National Pediatric Rheumatologic Database. Among those patients, 3-year outcome data were available for 133. These data included the clinical Juvenile Arthritis Disease Activity Score in 10 joints (JADAS-10) and the physician's global assessment score (on a numerical rating scale), as well as assessment of joint involvement, growth retardation, and patient-reported outcomes. RESULTS: The median clinical JADAS-10 declined significantly, from 7 in 2000 to 2 in 2013, while the proportion of patients with inactive disease increased from 19% in 2000 to 41% in 2013. The rate of treatment with systemic glucocorticoids and disease-modifying antirheumatic drugs (DMARDs) remained stable from 2000 to 2013. By 2013, the proportion of patients with systemic JIA who were treated with biologic DMARDs had increased to 20%. At 3-year follow-up, 72% of patients with systemic JIA had inactive disease, and 77% had no functional limitations. Growth retardation was associated with persistently high disease activity and continuing treatment with systemic glucocorticoids. At the 3-year follow-up, one-third of patients were still being treated with systemic glucocorticoids. CONCLUSION: The proportion of patients with inactive disease has increased over the past decade. Possible explanations may include improved access to specialized care, additional treatment options, and earlier or faster step-up treatment. However, challenges in the management of systemic JIA remain, as ∼30% of patients continue to present with ongoing active disease.

Does ß-Cell Autoimmunity Play a Role in Cystic Fibrosis-Related Diabetes? Analysis Based on the German/Austrian Diabetes Patienten Verlaufsdokumentation Registry.

OBJECTIVE: Research on ß-cell autoimmunity in cystic fibrosis (CF)-related diabetes (CFRD) is still rare. We aimed to analyze the frequency of ß-cell autoimmunity and the influence on age at diabetes onset, insulin requirement, type of insulin therapy, and hypoglycemic or ketoacidotic events in patients with CFRD compared with antibody-negative patients with CFRD in the Diabetes Patienten Verlaufsdokumentation (DPV) registry. RESEARCH DESIGN AND METHODS: We analyzed data of 837 patients with CFRD in the German/Austrian DPV database by multivariable mixed-regression modeling. RESULTS: In our cohort, 8.5% of patients with CFRD (n = 72) were found to be ß-cell antibody positive. There was a female preponderance in this patient group: 65.3 vs. 57.6%. Diabetes onset (median [interquartile range]) was earlier (14.00 [10.15-15.90] vs. 16.10 [13.50-21.20] years; P < 0.005), and insulin dose/kg body weight was higher (0.95 [0.61-1.15] vs. 0.67 [0.33-1.04] IU/kg; P < 0.05). There were also differences in the type of insulin treatment. Insulin pump therapy was used significantly more often in patients with CFRD with ß-cell autoimmunity (18.2 vs. 6.4%; P < 0.05). The differences for multiple daily injections (ICT) and conventional therapy (CT) were not significant (ICT: 67.7 vs. 79.0%; CT: 15.2 vs. 14.6). Oral antidiabetic agents were rarely used in both groups. Rate of severe hypoglycemia with coma and rate of ketoacidosis were higher in antibody-positive patients (hypoglycemia with coma: 8.0 vs. 1.4, P < 0.05; ketoacidosis: 9.3 vs. 0.9, P < 0.05). CONCLUSIONS: Presence of ß-cell autoantibodies in our cohort of patients with CFRD (8.5%) appeared to be greater than in the general population and was associated with female sex, earlier onset of diabetes, and higher insulin requirement. Insulin pump therapy was used significantly more often in patients with ß-cell antibodies. Severe hypoglycemia and ketoacidosis were significantly more frequent in CFRD with ß-cell autoimmunity compared with ß-cell antibody-negative patients with CFRD.

Carbohydrate intake and insulin requirement in children, adolescents and young adults with cystic fibrosis-related diabetes: A multicenter comparison to type 1 diabetes.

BACKGROUND & AIMS: In cystic fibrosis-related diabetes (CFRD), energy needs differ from type 1 (T1D) or type 2 diabetes, and endogenous insulin secretion is not totally absent. We analyzed whether daily carbohydrate intake, its diurnal distribution and insulin requirement per 11 g of carbohydrate differ between CFRD and T1D. METHODS: Anonymized data of 223 CFRD and 36,780 T1D patients aged from 10 to <30 years from the multicenter diabetes registry DPV were studied. Carbohydrate intake and insulin requirement were analyzed using multivariable regression modeling with adjustment for age and sex. Moreover, carbohydrate intake was compared to the respective recommendations (CFRD: energy intake 130% of general population with 45% carbohydrates; T1D: carbohydrate intake 50% of total energy). RESULTS: After demographic adjustment, carbohydrate intake (238 ± 4 vs. 191 ± 1 g/d, p < 0.001) and meal-related insulin (0.52 ± 0.02 vs. 0.47 ± 0.004 IU/kg*d, p = 0.001) were higher in CFRD, whereas basal insulin (0.27 ± 0.01 vs. 0.38 ± 0.004 IU/kg*d, p < 0.001) and total insulin requirement per 11 g of carbohydrate (1.15 ± 0.06 vs. 1.70 ± 0.01 IU/d, p < 0.001) were lower compared to T1D. CFRD patients achieved 62% [Q1;Q3: 47; 77] of recommended carbohydrate intake and T1D patients 60% [51; 71] of age- and gender-specific recommended intake (p < 0.001). CFRD and T1D patients had a carbohydrate intake below healthy peers (79% [58; 100] and 62% [52; 74], p < 0.001). The circadian rhythm of insulin sensitivity persisted in CFRD and the diurnal distribution of carbohydrates was comparable between groups. CONCLUSIONS: In pediatric and young adult patients, carbohydrate intake and insulin requirement differ clearly between CFRD and T1D. However, both CFRD and T1D patients seem to restrict carbohydrates.

Pharmacokinetics of meloxicam in patients with juvenile rheumatoid arthritis.

The pharmacokinetics of a meloxicam suspension were studied in 18 children with juvenile rheumatoid arthritis. Children received a single 0.25-mg/kg dose up to a maximum of 15 mg. Pharmacokinetic parameters after the first dose were calculated by noncompartmental methods. Geometric mean (percent coefficient of variation for geometric mean [gCV]) C(max), AUC(0- infinity ), apparent clearance, apparent volume of distribution, and elimination half-life values were 1.24 microg/mL (47% gCV), 25.6 microg x h/mL (81% gCV), 0.17 mL/min/kg (83% gCV), 0.19 L/kg (63% gCV), and 13.4 hours (54% gCV) in the younger group and 1.89 microg/mL (25% gCV), 35.8 microg x h/mL (21% gCV), 0.12 mL/min/kg (23% gCV), 0.13 L/kg (22% gCV), and 12.7 hours (21% gCV) for the older group, respectively. Area under the curve, volume of distribution, and clearance tended to be higher in the younger group, whereas elimination half-lives were similar. A post hoc comparison to pharmacokinetic data in adults revealed no relevant differences. Thus, a common body weight-normalized dose is considered appropriate for children older than 2 years.

Improvement in health-related quality of life for children with juvenile idiopathic arthritis after start of treatment with etanercept.

OBJECTIVE: Improvement in health-related quality of life (HRQOL) is an important therapy goal in the treatment of patients with juvenile idiopathic arthritis (JIA). We investigated the 12-month course of HRQOL in patients with JIA after the start of therapy with etanercept and identified its determining factors. METHODS: Children with JIA were enrolled in the BiKer (Biologics in Pediatric Rheumatology) registry at the start of etanercept treatment. Children were prospectively followed in the first year of treatment and completed the Pediatric Quality of Life Inventory (PedsQL) at each occasion. The change in HRQOL was investigated by random-effect regression models. The time-varying variables pain and inactive disease were used for predicting the change in HRQOL. Inactive disease was defined by the Wallace et al criteria and pain was assessed on a visual analog scale (range 0-100). RESULTS: The children (n = 61) had a mean age of 10.6 years and a mean disease duration of 3.4 years at the start of etanercept. The mean PedsQL total score was 75. The PedsQL total score increased at a rate of 2.8 units per month (P < 0.001) in the first 6 months of treatment, up to a level of 89.7. A low HRQOL score was significantly highly associated with the number of tender joints, functional restrictions, pain, disease activity, and the existence of a comorbid condition at baseline. Inactive disease and reduced pain predicted better HRQOL under etanercept treatment. CONCLUSION: HRQOL was dramatically improved in children who started etanercept treatment. Inactive disease and lower pain were important predictors for improvement of HRQOL over time.

Distinct effects of methotrexate and etanercept on the B cell compartment in patients with juvenile idiopathic arthritis.

OBJECTIVE: B cells have been shown to play an important role in the pathogenesis of rheumatoid arthritis and juvenile idiopathic arthritis (JIA). Current treatments include the disease-modifying antirheumatic drugs methotrexate (MTX) and tumor necrosis factor α inhibition with etanercept. This study was undertaken to determine how these drugs influence the B cell compartment in patients with JIA. METHODS: B cell subpopulations and follicular helper T (Tfh) cells in the peripheral blood of JIA patients were investigated by multicolor flow cytometry. Serum immunoglobulin and BAFF levels were determined by enzyme-linked immunosorbent assay. RESULTS: There was a significant decrease in transitional B cells and significantly lower serum immunoglobulin levels in patients receiving MTX than in untreated patients and those receiving etanercept. In contrast, etanercept treatment had no effect on most of the B cell subpopulations, but resulted in significantly lower BAFF levels and increased numbers of Tfh cells. Thus, our findings indicate an unexpected and previously unknown direct effect of low-dose MTX on B cells, whereas etanercept had a more indirect influence. CONCLUSION: Our results contribute to a better understanding of the potency of MTX in autoantibody-mediated autoimmune disease and present a possible mechanism of prevention of the development of drug-induced antibodies to biologic agents. The finding that MTX and etanercept affect the B cell compartment differently supports the notion that combination therapy with etanercept and MTX is more effective than monotherapy.