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Objective The objective of this study was to use real-world data to evaluate the effectiveness and safety of canakinumab in Italian patients with systemic JIA (sJIA). Methods A retrospective multicentre study of children with sJIA was performed. Clinical features, laboratory parameters and adverse events were collected at baseline, and 6 and 12 months after starting canakinumab. The primary outcome measure of effectiveness was clinically inactive disease (CID) off glucocorticoids (GCs) treatment at 6 months. Results A total of 80 children from 15 Italian centres were analysed. Of the 12 patients who started canakinumab in CID while receiving anakinra, all maintained CID. Of the 68 with active disease at baseline, 57.4% achieved CID off GCs at 6 months and 63.8% at 12 months. In univariate analysis, the variables significantly related to non-response were number of active joints (NAJs) ≥5, history of macrophage activation syndrome (MAS) and disease duration. Multivariate analysis confirmed the association between non-response and NAJs ≥5 [odds ratio (OR) 6.37 (95% CI: 1.69, 24.02), P = 0.006] and between non-response and history of MAS [OR 3.53 (95% CI: 1.06, 11.70), P = 0.039]. No serious adverse events were recorded in this series. There were two cases of MAS during canakinumab, leading to a rate of 2.9 episodes per 100 patient years. Conclusion We have confirmed, using real-world data, the efficacy of canakinumab in sJIA in a multicentric cohort. History of MAS and higher NAJ were associated with lower probability of achieving CID.

Objective To compare clinical features and treatments of patients with systemic JIA (sIJA) and adult-onset Still’s disease (AOSD). Methods The clinical charts of consecutive patients with sJIA by International League of Association of Rheumatology criteria or AOSD by Yamaguchi criteria were reviewed. Patients were seen at a large paediatric rheumatology referral centre or at 10 adult rheumatology academic centres. Data collected included clinical manifestations, inflammation biomarkers, systemic score, macrophage activation syndrome (MAS), parenchymal lung disease, disease course, disability, death and medications administered. Results A total of 166 patients (median age at diagnosis 5 years) with sJIA and 194 patients with AOSD (median age at diagnosis 41 years) were included. The frequency of fever, rash, arthralgia, abdominal pain, MAS, parenchymal lung disease and increased acute phase reactants and ferritin were comparable between the two cohorts. Patients with sJIA had a higher prevalence of arthritis, whereas patients with AOSD had experienced leucocytosis and extra-articular organ involvement more frequently. Patients with AOSD were given more commonly low-dose corticosteroids, whereas biologic DMARDs were administered first-line more frequently in patients with sJIA. Conclusion We found remarkable disparities in the prevalence of clinical manifestations between the two illnesses, which may partly depend on their classification by different criteria.

Introduction: Systemic juvenile idiopathic arthritis (sJIA) accounts for 10-20% of all patients with JIA. The demonstration of a key role of IL-1 and IL-6 in the pathogenesis of the disease, led to consider sJIA an autoinflammatory disease: this explain the successfully use of IL-1 and IL-6 inhibitors. While the efficacy and safety of anakinra in sJIA is widely documented, there are no reports on large series of patients treated with canakinumab outside of the setting of clinical trials. Objectives: The aim of this study was to evaluate clinical response rate and disease course of canakinumab in Italian cohort of patients with sJIA. Methods: This is a retrospective multicenter study. Demographic features, previous medical history and therapies was evaluated for each patients. Clinical features, laboratory parameters and adverse events were collected at baseline and after 6 months from starting canakinumab. Clinically inactive disease (CID) was defined according to Wallace criteria. Results: We enrolled 82 (50 F) patients with sJIA treated with canakinumab from 2006 to 2020; 75 of them reached a follow up of 6 months. At baseline 49 patients (59.8%), of which 36 in active disease (AD) and 13 in CID, were previously treated with anakinra, while 33 patients in AD (40.2%) were naïve. At 6 months of follow-up 51/75 patients (68%) met criteria of CID off-glucocorticoids, including all 13 patients in CID at baseline, 19 patients in AD previously treated with anakinra and 19 patients naïve. Twenty-four patients (32%) maintained AD. To evaluated if the response to canakinumab might be related to the baseline features we excluded 13 patients in CID at baseline; we divided the 62 patients in responders (38/62, 61.3%) and non-responders (24/62, 38.7%). There were no significant differences between the two groups regarding demographic, clinical and laboratory parameters, except for a higher number of active joints (p=0.021) and for a greater use of disease-modifying antirheumatic drugs (DMARDs) (p

Systemic juvenile idiopathic arthritis (sJIA) is an autoinflammatory disease characterised by fever and arthritis. We describe the case of a 14-year-old girl hospitalised with fever associated with rash, myalgia, arthralgia and polyarticular involvement. Examinations revealed increased levels of C-reactive protein, erythrocyte sedimentation rate, ferritin, triglycerides, leukocytes, neutrophils, lactate dehydrogenase, fibrinogen, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and γ-glutamyl transferase (GGT). Bone marrow biopsy showed polyclonal leukocyte activation. A genetic study revealed a heterozygous mutation of the MEFV gene, c.442G>C (E148Q), which is typical of familial Mediterranean fever. However, the genetic pattern was not associated with a history of recurrent fever, aphthous ulcers of the mouth, abdominal pain, arthralgia and rash. Therefore, a diagnosis of sJIA was made. The patient did not respond to non-steroidal anti-inflammatory drugs. Corticosteroids improved biochemical examinations; however, AST, ALT, GGT and glycaemia remained elevated and adverse effects of corticosteroid treatment became evident and therefore corticosteroids were withdrawn. Canakinumab (150mg/4weeks subcutaneously) was initiated. Biochemical data returned to normal values and clinical symptoms resolved. After 2.5years of canakinumab treatment, complete disease remission allowed the prolongation of intervals between doses. When the intervals were longer than 10weeks we discontinued the treatment. The patient is still in remission 2years after canakinumab withdrawal.

Introduction: The advent of biologic agents has revolutionized therapeutic approaches in systemic juvenile idiopatic arthritis (sJIA) as their introduction has been shown to modify disease course and improve overall outcomes, particularly when initiated early. Few studies have reported the drug retention rate (DRR) of biologic drugs in JIA, and none of them has specifically investigated the DRR of interleukin (IL)-1 inhibitors on sJIA. Objectives: The primary aim of the study was to examine the overall DRR of IL-1 blockers in sJIA patients. Secondary aims of our study were to: (i) explore the influence of biologic line of treatment, adverse events (AEs), type of anti-IL-1 agent and the concomitant use of conventional disease modifying anti-rheumatic drugs (cDMARDs) on DRR; (ii) find eventual predictive factors associated with events leading to drug discontinuation. The corticosteroid sparing effect and the impact of disease duration and treatment delay on survival constituted ancillary aims. Methods: sJIA patients – diagnosed according to the revised International League of Association for Rheumatology (ILAR) criteria – treated with anakinra (ANA) and canakinumab (CAN) were enrolled in 15 Italian tertiary referral centers. Demographic, clinical and therapeutic data collected from medical records were retrospectively collected and statistically analyzed. Results: Seventy seven patients were enrolled for a total of 86 treatment courses. The cumulative retention rate of the IL-1 inhibitors at 12-, 24-, 48-, and 60-months of follow-up was 79.9, 59.5, 53.5, and 53.5%, respectively, without any statistically significant differences between ANA and CAN (p = 0.056), and between patients treated in monotherapy compared to the subgroup co-administered with conventional immunosuppressors (p = 0.058). On the contrary, significant differences were found between biologic-naive patients and those previously treated with biologic drugs (p = 0.038) and when distinguishing according to AEs occurrence (p = 0.04). In regression analysis, patients pre-treated with other biologics (HR = 3.357 [CI: 1.341–8.406], p = 0.01) and those experiencing AEs (HR = 2.970 [CI: 1.186–7.435], p = 0.020) were associated with a higher hazard ratio of IL-1 inhibitors withdrawal. The mean treatment delay was significantly higher among patients discontinuing IL-1 inhibitors (p = 0.0002). Conclusion: Our findings suggest an excellent overall DRR for both ANA and CAN that might be further augmented by paying attention to AEs and employing these agents as first-line biologics in an early disease phase.

Introduction: Macrophage activation syndrome (MAS) is a severe, hyperinflammatory life-threatening syndrome, generally complicating different rheumatic diseases. Despite the severity of the disease, little is known about the pathogenic mechanisms and, thus, possible targeted therapies in the management of these patients. Areas covered: In this review, we aimed to update the current pathogenic knowledge of MAS, during rheumatic diseases, focusing mainly on immunologic abnormalities and on new possible therapeutic strategies. Expert commentary: The difficult pathogenic scenario of MAS, in which genetic defects, predisposing diseases, and triggers are mixed together with the high mortality rate, make it difficult to manage these patients. Although most efforts have been focused on investigating the disease in children, in recent years, several studies are trying to elucidate the possible pathogenic mechanism in adult MAS patients. In this context, genetic and immunological studies might lead to advances in the knowledge of pathogenic mechanisms and possible new therapeutic targets. In the future, the results of ongoing clinical trials are awaited in order to improve the management and, thus, the survival of these patients.