Objectives To describe risk factors for inflammatory bowel disease (IBD) development in a cohort of children with juvenile idiopathic arthritis (JIA). Methods JIA patients who developed IBD were identified from the international Pharmachild register. Characteristics were compared between IBD and non-IBD patients and predictors of IBD were determined using multivariable logistic regression analysis. Incidence rates of IBD events on different disease-modifying anti-rheumatic drugs (DMARDs) were calculated, differences between therapies were expressed as relative risks (RR). Results Out of 8,942 patients, 48 (0.05%) developed IBD. These were more often male (47.9% vs 32.0%) and HLA-B27 positive (38.2% vs 21.0%) and older at JIA onset (median 8.94 vs 5.33 years) than patients without IBD development. They also had more often a family history of autoimmune disease (42.6% vs 24.4%) and enthesitis-related arthritis (ERA) (39.6% vs 10.8%). The strongest predictors of IBD on multivariable analysis were ERA (OR: 3.68, 95% CI: 1.41–9.40) and a family history of autoimmune disease (OR: 2.27, 95% CI: 1.12–4.54). Compared with methotrexate monotherapy, the incidence of IBD on etanercept monotherapy (RR: 7.69, 95% CI: 1.99–29.74), etanercept with methotrexate (RR: 5.70, 95% CI: 1.42–22.77) and infliximab (RR: 7.61, 95% CI: 1.27–45.57) therapy was significantly higher. Incidence on adalimumab was not significantly different (RR: 1.45, 95% CI: 0.15–13.89). Conclusion IBD in JIA was associated with ERA and a family history of autoimmune disease. An increased IBD incidence was observed for etanercept therapy regardless of concomitant methotrexate use.

Objectives The presence of melanoma differentiation-associated protein 5 (MDA5) antibodies in patients with dermatomyositis (DM) is associated with the development of a rapidly progressive interstitial lung disease (RPILD), unresponsive to conventional treatment. We characterize patients and provide more insight into potential biomarkers to identify patients with RPILD. Methods Patients diagnosed with anti-MDA5 positive DM between December 2015 and November 2017 were included in this study. Clinical data were retrospectively retrieved from medical records. 180 immune-related markers were measured in sera of 16 patients and 15 healthy controls using proximity extension assay based technology. Results Twenty patients were included, with a median time from symptoms till diagnosis of 4 months. All patients had clinically amyopathic DM. Interstitial lung disease (ILD) was present at diagnosis in 94% of the patients, 45% presented with RPILD. The mortality rate was 35% within 4 months after diagnosis and respiratory failure was the main cause of death in these patients. Furthermore, unsupervised analysis revealed that patients with RPILD show clearly different inflammatory serum profiles than healthy controls. In addition, in comparison to healthy controls, the interferon, Interleukin (IL)1, IL10 and IL18 signalling pathways are different regulated in anti-MDA5 positive patients. Conclusion In this Dutch anti-MDA5 positive CADM cohort, one third of the patients died due to RPILD soon after diagnosis, which underlines the severity of this disease. In addition, we have found several possible pathways that are differentially regulated in RPILD vs no RPILD DM and healthy controls. These markers await further validation before clinical use.

ObjectiveThe aim of this study was to evaluate the response of ear, nose and throat (ENT) symptoms to different immunosuppressive therapies in patients with ANCA-associated vasculitis (AAV).MethodsIn this cohort study, AAV patients treated between January 2010 and April 2020 at two Dutch hospitals were included. Clinical, histological and laboratory data were collected retrospectively. ENT involvement was defined as 1) at least one ENT symptom according to the Birmingham vasculitis activity score version 3 (BVAS-3) and/or 2) presence of saddle nose deformity. Associations between therapy and ENT activity were assessed using logistic regression analysis.ResultsA total of 320 AAV patients were included, of which 209 (65.3%) had ENT involvement at some point throughout the disease course. In these 209 patients, median age at disease onset was 52.0 years (IQR 22) and 45.5% was male. Median BVAS-3 was 12 (IQR 12) at diagnosis. Despite immunosuppressive therapy 50.0% (N=77) of the patients had ENT symptoms at relapse and 29.1% (N=59) had ENT activity at last visit. No statistically significant difference in ENT activity at last visit was observed between patients treated with oral or intravenous cyclophosphamide (N=137) compared to rituximab (N=55) (adjusted OR 0.59 (95% CI 0.33-1.06), p=0.077). Lower age at disease onset and female sex were independently associated with ENT activity at last follow-up.ConclusionIn this cohort cyclophosphamide and rituximab therapy had similar therapeutic effects on ENT symptoms in AAV. Persistent ENT activity is a common feature despite immunosuppressive therapy.

BackgroundJuvenile idiopathic arthritis (JIA) has a reported prevalence varying from 16 to 150 per 100,000 patients and it thereby is the most frequent chronic rheumatologic disease presenting in childhood. Inflammatory bowel disease (IBD) is an auto-inflammatory disease that can develop in patients with JIA. Results from multiple studies suggest an association between therapy with Etanercept (ETN) and occurrence of IBD in patients with JIA, which may or may not be counteracted by methotrexate.ObjectivesThe aim of this study was to describe characteristics of JIA patients who developed IBD and to evaluate a possible relationship between IBD onset and medication use at IBD onset.MethodsPharmachild, the largest international JIA registry, was used for this study. Patients were enrolled via members of the Paediatric Rheumatology INternational Trials Organisation (PRINTO). The registry contains both retrospective and prospective data.ResultsA total of 8,309 patients were included in this study. 290 gastrointestinal disorders were reported in 260 patients. 50 cases in 47 patients were classified as IBD or suspected IBD.Age at JIA onset was significantly higher in patients who developed IBD (9.1 vs 7.1 years p=0.002), and female predominance was lower (48.9% versus 67.6% p=0.011). Enthesitis related arthritis (ERA) was the JIA subtype in 40.4% of the patients who developed IBD.In 14 out of 47 patients more detailed information about IBD disease onset was available, such as date of disease onset and medication used at that time. 71.4% of all 14 patients used etanercept and 50.0% used MTX 3 months prior or at IBD onset. Etanercept exposure prior to IBD onset varied from no exposure to 6.39 years with a median of 1.3 years. Methotrexate exposure prior to disease onset varied from no exposure to 8.10 years with a median of 2.9 years.Information regarding quality of life was available for 2,752 patients of which 17 IBD patients. Quality of life, both physical and psychosocial, was significantly lower in patients who developed IBD patients (p=0.018 and p=0.046 respectively).ConclusionIn this study ERA patients were more at risk of developing IBD and 71.4% used etanercept while developing IBD. We did not find a protective role of MTX since 50.0% of patients with available data developed IBD while using MTX. Lastly, IBD has an important physical and psychosocial impact on quality of life.Reference[1] Swart JF; Giancane G; Horneff G; Magnusson B; Hofer M; Alexeeva E; Panaviene V; Bader-Meunier B; Anton J; Nielsen S; De Benedetti F; Kamphuis S; Stanevicha V; Trachana M; Ailioaie LM; Tsitsami E; Klein A; Minden K; Foeldvari I; Haas JP; Klotsche J; Horne. Pharmacovigilance in juvenile idiopathic arthritis patients treated with biologic or synthetic drugs: combined data of more than 15,000 patients from pharmachild and national registries. Arthritis Res Ther. 2018;Disclosure of InterestsRoline Krol: None declared, Joost F. Swart: None declared, Gabriella Giancane: None declared, Sytze De Roock: None declared, Troels Herlin: None dec...

Background: Ear, nose and throat (ENT) manifestations are common in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), yet how to treat these manifestations remains controversial. Therefore, we systematically reviewed the literature on the efficacy of therapies on ENT manifestations in AAV. Methods: A systematic review was conducted in accordance with the PRISMA guidelines, searching Medline, Embase and Cochrane libraries, including clinical studies between January 2005 and January 2022, in adults with AAV and ENT involvement, reporting on the effects of local and systemic therapy. The critical appraisal was performed using tools provided by the Cochrane Library and the level of evidence (LoE) was scored according to the Oxford Centre for Evidence-based Medicine. Results: After screening 5609 identified studies, 136 full-text articles were assessed. Finally, 31 articles were included for critical appraisal and data-extraction. Nearly all studies (n = 29) were retrospective and scored low on LoE. The included studies evaluated local interventions (n = 11), glucocorticoids combined with conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) (n = 8), rituximab (n = 6), or mepolizumab (n = 6). Due to heterogeneity across studies meta-analysis was not performed. Four studies on mepolizumab for sinonasal symptoms (n = 92) showed response in 33–100% and relapse in 35%. Local therapy for subglottic stenosis was effective in 80–100% of patients in 11 studies (n = 157), but relapses were common (up to 83%). In five studies, hearing improvement was observed in 56–100%, with better outcomes when glucocorticoids were combined with csDMARDs compared to glucocorticoids only. Conclusion: Response rates of ENT manifestations varied widely in studies and relapses were observed frequently. Heterogeneity among studies impaired comparison.