Mortality rates are increased in patients with systemic juvenile idiopathic arthritis

Davies, Rebecca; Southwood, T. R. E.; Kearsley‐Fleet, Lianne; Baildam, Eileen; Beresford, Michael W.; Foster, Helen; Douglas, Sharon; Thomson, Wendy; Cock, Diederik De; Hyrich, Kimme L

doi:10.1136/archdischild-2016-311571

Cited by 17 publications

(13 citation statements)

References 3 publications

(1 reference statement)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The period of follow-up after LD diagnosis was variable (median 1.7 years; IQR 0.75–3 years). Survival was drastically lower in the LD cohort (mortality: 159/1000 person-years; figure 5) than in a UK cohort of patients with sJIA who required biologic agents (mortality: 3.9/1000 person-years) 45. The predominant cause of death in our cohort was reported as diffuse LD (12 of 22 deaths), with MAS in 5 of 12 (online supplementary table S7).…”

Section: Resultsmentioning

confidence: 60%

Emergent high fatality lung disease in systemic juvenile arthritis

et al. 2019

View full text Add to dashboard Cite

ObjectiveTo investigate the characteristics and risk factors of a novel parenchymal lung disease (LD), increasingly detected in systemic juvenile idiopathic arthritis (sJIA).MethodsIn a multicentre retrospective study, 61 cases were investigated using physician-reported clinical information and centralised analyses of radiological, pathological and genetic data.ResultsLD was associated with distinctive features, including acute erythematous clubbing and a high frequency of anaphylactic reactions to the interleukin (IL)-6 inhibitor, tocilizumab. Serum ferritin elevation and/or significant lymphopaenia preceded LD detection. The most prevalent chest CT pattern was septal thickening, involving the periphery of multiple lobes ± ground-glass opacities. The predominant pathology (23 of 36) was pulmonary alveolar proteinosis and/or endogenous lipoid pneumonia (PAP/ELP), with atypical features including regional involvement and concomitant vascular changes. Apparent severe delayed drug hypersensitivity occurred in some cases. The 5-year survival was 42%. Whole exome sequencing (20 of 61) did not identify a novel monogenic defect or likely causal PAP-related or macrophage activation syndrome (MAS)-related mutations. Trisomy 21 and young sJIA onset increased LD risk. Exposure to IL-1 and IL-6 inhibitors (46 of 61) was associated with multiple LD features. By several indicators, severity of sJIA was comparable in drug-exposed subjects and published sJIA cohorts. MAS at sJIA onset was increased in the drug-exposed, but was not associated with LD features.ConclusionsA rare, life-threatening lung disease in sJIA is defined by a constellation of unusual clinical characteristics. The pathology, a PAP/ELP variant, suggests macrophage dysfunction. Inhibitor exposure may promote LD, independent of sJIA severity, in a small subset of treated patients. Treatment/prevention strategies are needed.

show abstract

Section: Resultsmentioning

confidence: 60%

Emergent high fatality lung disease in systemic juvenile arthritis

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Systemic onset-juvenile idiopathic arthritis (sJIA) is the most severe and distinct category of JIA due to its unique pathogenesis, severity and disproportionately high morbidity and mortality rates when compared to other JIA subtypes (Ruperto et al, 2012; Minoia et al, 2014; Kumar, 2016; Davies et al, 2017). This condition is distinguished by its unique clinical features and treatment responses, that make it similar to the autoinflammatory diseases, a large family of pathologic entities caused by dysregulation of the innate immune system leading to recurrent or continuous inflammation (Rigante, 2017, 2018).…”

Section: Introductionmentioning

confidence: 99%

Drug Retention Rate and Predictive Factors of Drug Survival for Interleukin-1 Inhibitors in Systemic Juvenile Idiopathic Arthritis

et al. 2019

View full text Add to dashboard Cite

Background and Objectives: Few studies have reported the drug retention rate (DRR) of biologic drugs in juvenile idiopathic arthritis (JIA), and none of them has specifically investigated the DRR of interleukin (IL)-1 inhibitors on systemic JIA (sJIA). This study aims to describe IL-1 inhibitors DRR and evaluate predictive factors of drug survival based on data from a real-world setting concerning sJIA.Methods: Medical records from sJIA patients treated with anakinra (ANA) and canakinumab (CAN) were retrospectively analyzed from 15 Italian tertiary referral centers.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 adverse events (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).Conclusions: 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.

show abstract

“…3,5,[22][23][24][25] Over the past decade, the experience with autologous stem cell transplantation (ASCT) for patients with refractory JIA has produced valuable data. The biological mechanisms by which ASCT works were shown to be not only by the eradication of autoreactive lymphocytes with immunosuppressive conditioning and T-cell depletion, but also importantly by restoration of the chimeric T-cell receptor (TCR) repertoire and CD4…”

Section: Discussionmentioning

confidence: 99%