IL-1 Inhibition in Systemic Juvenile Idiopathic Arthritis

Systemic juvenile idiopathic arthritis (sJIA) is the form of childhood arthritis whose treatment is most challenging. The demonstration of the prominent involvement of interleukin (IL)-1 in disease pathogenesis has provided the rationale for the treatment with biologic medications that antagonize this cytokine. The three IL-1 blockers that have been tested so far (anakinra, canakinumab, and rilonacept) have all been proven effective and safe, although only canakinumab is currently approved for use in sJIA. The studies on IL-1 inhibition in sJIA published in the past few years suggest that children with fewer affected joints, higher neutrophil count, younger age at disease onset, shorter disease duration, or, possibly, higher ferritin level may respond better to anti-IL-1 treatment. In addition, it has been postulated that use of IL-1 blockade as first-line therapy may take advantage of a window of opportunity, in which disease pathophysiology can be altered to prevent the occurrence of chronic arthritis. In this review, we analyze the published literature on IL-1 inhibitors in sJIA and discuss the rationale underlying the use of these medications, the results of therapeutic studies, and the controversial issues

The Silent Epidemic of Diabetic Ketoacidosis at Diagnosis of Type 1 Diabetes in Children and Adolescents in Italy During the COVID-19 Pandemic in 2020

To compare the frequency of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes in Italy during the COVID-19 pandemic in 2020 with the frequency of DKA during 2017-2019

Remission, minimal disease activity, and acceptable symptom state in juvenile idiopathic arthritis: Defining criteria based on the juvenile arthritis disease activity score

To determine cutoff values for defining remission, minimal disease activity, and parent and child acceptable symptom state in juvenile idiopathic arthritis (JIA) using the Juvenile Arthritis Disease Activity Score (JADAS).For the selection of cutoff values, data from a clinical database including 609 children with JIA were used. Optimal cutoff values were determined against external criteria by calculating the 75th percentile of cumulative score distribution and through receiver operating characteristic curve analysis. External criteria included formal definitions of inactive disease and minimal disease activity, subjective rating of remission by physicians, parents, and children, and rating of acceptable symptom state by parents and children. The choice of cutoffs was made based on clinical and statistical grounds. Cross-validation was performed using 4 JIA patient samples that included a total of 1,323 patients, and was based on assessment of construct, discriminant, and predictive validity.With all versions of the JADAS, the cutoff score for classifying a patient as having inactive disease was 1, whereas the cutoff for classification of minimal disease activity was 2 for oligoarticular JIA and 3.8 for polyarticular JIA. Cutoffs for physicians', parents', and children's subjective rating of remission ranged from 2 to 2.3. Cutoffs for acceptable symptom state ranged from 3.2 to 5.4 for parents and from 3 to 4.5 for children. Results of cross-validation analyses strongly supported the selected cutoff values.Cutoff values for classifying various disease states in JIA using the JADAS were developed. In cross-validation analyses, they proved to have good construct and discriminant validity and ability to predict disease outcome

A retrospective analysis of 24-month real-world glucose control for children and adolescents with type 1 diabetes using the MiniMed™ 670G insulin pump

The MiniMed™ 670G insulin pump was the first hybrid closed-loop (HCL) system available for clinical use. Data on metabolic outcomes in children, adolescents and young adults over the first 12 months with auto-mode use of this device are available, but no data with longer follow-up have been published. We aimed to assess the metabolic outcomes in children and adolescents using the MiniMed™ 670G for 24 months

A retrospective analysis of 24-month real-world glucose control for children and adolescents with type 1 diabetes using the MiniMed™ 670G insulin pump

The MiniMed™ 670G insulin pump was the first hybrid closed-loop (HCL) system available for clinical use. Data on metabolic outcomes in children, adolescents and young adults over the first 12 months with auto-mode use of this device are available, but no data with longer follow-up have been published. We aimed to assess the metabolic outcomes in children and adolescents using the MiniMed™ 670G for 24 months

A prediction rule for polyarticular extension in oligoarticular-onset juvenile idiopathic arthritis

To search for predictors of polyarticular extension in children with oligoarticular-onset juvenile idiopathic arthritis (JIA) and to develop a prediction model for an extended course

Analysis of arthritis flares after achievement of inactive disease with methotrexate monotherapy in juvenile idiopathic arthritis

To investigate the frequency of arthritis flare and factors affecting occurrence of flare in children with juvenile idiopathic arthritis (JIA) who achieved inactive disease (ID) with methotrexate (MTX) monotherapy

Glucometrics and device satisfaction in children and adolescents with type 1 diabetes using different treatment modalities: A multicenter real-world observational study

Aims: To analyze metabolic outcomes, diabetes impact and device satisfaction in children and adolescents with type 1 diabetes in Italy who used different treatment modalities for diabetes care in a real-life context. Methods: In this multicenter, nationwide, cross-sectional study, 1464 participants were enrolled at a routine visit. The following treatment modalities were considered MDI + SMBG; MDI + CGM; Sensor Augmented Pump Therapy; predictive management of low glucose; Hybrid Closed Loop (HCL); Advanced Hybrid Closed Loop (AHCL). Health related quality of life was evaluated by the Italian version of the Diabetes Impact and Device Satisfaction Scale (DIDS) questionnaire. Results: Patients treated with AID systems were more likely to have HbA1c ≤ 6.5 %, higher percentage of time with glucose levels between 70 and 180 mg/dL, lower percentage of time with glucose levels above 180 mg/dL, higher device satisfaction, and reduced impact of diabetes. All the therapeutic modalities with respect to MDI + CGM, except for MDI + SMBG, contributed to increase the device satisfaction. HCL and AHCL respect to MDI + CGM were associated with lower diabetes impact. Conclusion: Real-life use of automated insulin delivery systems is associated with reduced type 1 diabetes impact, increased device satisfaction, and achievement of glycemic goals

Oral or subcutaneus methotrexate: comparison of the efficacy in inducing sustained disease remission in children with oligoarticular JIA

Introduction: Methotrexate (MTX) is widely adopted as a first line treatment in moderate to severe forms of juvenile idiopathic arthritis (JIA), when NSAIDs and intra-articular corticosteroid injections are not sufficient to control joint disease. MTX is generally prescribed at 10-15 mg/m2 weekly and its administration can be either oral or parenteral (subcutaneous (SC) or intramuscular). Contrasting evidence is available in the literature about the difference in efficacy and safety of MTX, according to the route of administration. Objectives: Aim of the study is to compare the efficacy of oral versus SC MTX in inducing sustained disease remission in children with oligoarticular JIA enrolled in two prospective cohorts. Methods: Children with oligoarthritis included in 3 prospective studies were considered for inclusion: a) the TRIMECA trial (1), b) the MD-Paedigree study (2), c) the PharmaChild registry. Patient evaluated at the IRCCS Istituto Giannina Gaslini and at the Ospedale Pediatrico Bambino Gesù were included if they had received methotrexate treatment as a first line systemic medication within 6 months after disease onset and if a follow up of at least 12 month after treatment initiation was available. Patients were then grouped according to the route of MTX administration. Baseline demographic and disease features were compared between the 2 groups. Efficacy was assessed by comparing the rate of inactive disease (ID) and clinical remission on medication (CRM) at 12 months, the rate of patients changing the route of MTX administration or requiring a biologic medication due to treatment failure. Safety was assessed by comparing the frequency of treatment interruption due to side effects of MTX. Results: 79 patients were included in the study: 43 received oral MTX, 36 received SC MTX. At treatment initiation, disease duration was not different in the two groups; children receiving SC MTX were older at baseline (4.6 yrs vs. 2.5 yrs) and at disease onset (4.2 yrs vs. 2.3 yrs). Disease activity was comparable in the 2 groups, with a median of 2 active joints in both groups. Median MTX dose was 14.4 mg/m2 for oral MTX group and 15.2 mg/m2 for SC MTX (Mann-Whitney U test, p < 0.01). At 12 months, children receiving SC MTX achieved more frequently ID (84.9% vs 43.8%, Chi squared test p < 0.001) and CRM (54.5% vs 28.3%, p = 0.002). Patients in SC MTX group were more often prescribed a biologic medication (22.9% vs 6.5%, p = 0.024), but none of them were switched to the oral administration while 37% of children in oral MTX group were turned to SC MTX. One patient in both groups had MTX treatment suspended due to side effects. Conclusion: Our preliminary results support the evidence of an increased efficacy of MTX in inducing sustained disease remission when it is administered subcutaneously