Publications by authors named "Pierre Quartier"

164 Publications

Clinical effectiveness and safety of baricitinib for the treatment of juvenile idiopathic arthritis-associated uveitis or chronic anterior antinuclear antibody-positive uveitis: study protocol for an open-label, adalimumab active-controlled phase 3 clinical trial (JUVE-BRIGHT).

Trials 2021 Oct 9;22(1):689. Epub 2021 Oct 9.

Pediatric Immunology-Hematology and Rheumatology Unit, RAISE reference centre for rare diseases, Necker-Enfants Malades University Hospital, Assistance Publique-Hopitaux de Paris, IMAGINE Institute, Université de Paris, Paris, France.

Background: Juvenile idiopathic arthritis (JIA) is the most common pediatric rheumatic disease and the most common systemic disorder associated with uveitis in childhood. Uveitis is more common in JIA patients who are antinuclear antibody (ANA)-positive, have an early-onset disease, and have oligoarticular arthritis. JIA-associated uveitis (JIA-uveitis) is typically anterior, chronic, bilateral, nongranulomatous, and asymptomatic. Visual outcomes in JIA-uveitis have improved with current screening and treatment options; however, many patients fail to respond or do not achieve long-lasting remission. Baricitinib, an oral selective Janus kinase (JAK)1 and 2 inhibitor, may impact key cytokines implicated in the pathogenesis of JIA-uveitis or ANA-positive uveitis, representing a potential novel treatment option for disease management.

Methods: The multicenter, phase 3 trial will be conducted using an open-label Bayesian design. The study will enroll at least 20 and up to 40 patients aged 2 to <18 years with active JIA-uveitis or chronic ANA-positive uveitis without systemic features. At least 20 patients who have had an inadequate response or intolerance to methotrexate (MTX-IR), but not biologic disease-modifying antirheumatic drugs (bDMARDs), will be randomized (1:1) to open-label baricitinib or adalimumab. Approximately 20 additional patients who are MTX-IR or bDMARD inadequate responders will receive baricitinib treatment. Patients will be treated with once daily oral baricitinib at a fixed dose by age group (4 mg for patients aged ≥6 to <18 years and 2 mg for patients <6 years) or adalimumab (20 mg for patients weighing <30 kg and 40 mg for patients ≥30 kg) as a subcutaneous injection every 2 weeks. Treatment with stable background conventional synthetic DMARDs, low-dose corticosteroids, and/or nonsteroidal anti-inflammatory drugs is allowed. The primary endpoint is the proportion of patients with response at week 24. Patients may continue treatment for up to 5 years.

Discussion: This is the first pediatric clinical trial to assess the clinical effectiveness and safety of a JAK inhibitor in JIA-uveitis or chronic ANA-positive uveitis. A novel Bayesian design is used to assess the efficacy of baricitinib, including an adalimumab reference arm, in this small patient population with unmet medical need.

Trial Registration: EudraCT 2019-000119-10 . Registered on January 4, 2019; NCT04088409 . Registered on September 12, 2019.
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http://dx.doi.org/10.1186/s13063-021-05651-5DOI Listing
October 2021

Definition and Validation of the American College of Rheumatology 2021 Juvenile Arthritis Disease Activity Score Cutoffs for Disease Activity States in Juvenile Idiopathic Arthritis.

Arthritis Rheumatol 2021 Sep 28. Epub 2021 Sep 28.

Università degli Studi di Genova, Istituto Giannina Gaslini, IRCCS and Clinica Pediatrica e Reumatologia, Genoa, Italy.

Objective: To develop and validate new Juvenile Arthritis Disease Activity Score 10 (JADAS10) and clinical JADAS10 (cJADAS10) cutoffs to separate the states of inactive disease (ID), minimal disease activity (MiDA), moderate disease activity (MoDA), and high disease activity (HDA) in children with oligoarthritis and with rheumatoid factor-negative polyarthritis, based on subjective disease assessment by the treating pediatric rheumatologist.

Methods: The cutoffs definition cohort was composed of 1,936 patients included in the multinational Epidemiology, Treatment and Outcome of Childhood Arthritis (EPOCA) study. Using the subjective physician rating as an external criterion, 4 methods were applied to identify the cutoffs: mapping, Youden index, 90% specificity, and maximum agreement. The validation cohort included 4,014 EPOCA patients, patients from 2 randomized trials, and 88 patients from the PharmaChild registry. Cutoff validation was conducted by assessing discriminative and predictive ability.

Results: The JADAS10 cutoffs were 1.4, 4, and 13, respectively, for oligoarthritis and 2.7, 6, and 17, respectively, for polyarthritis. The cJADAS10 cutoffs were 1.1, 4, and 12, respectively, for oligoarthritis and 2.5, 5, and 16, respectively, for polyarthritis. The cutoffs discriminated strongly among different levels of pain and morning stiffness, between patients who were and those who were not prescribed a new medication, and between different levels of improvement in clinical trials. Achievement of ID and MiDA according to the new JADAS cutoffs at least twice in the first year of disease predicted better outcome at 2 years.

Conclusion: The 2021 JADAS and cJADAS cutoffs revealed good metrologic properties in both definition and validation samples, and are therefore suitable for use in clinical trials and routine practice.
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http://dx.doi.org/10.1002/art.41879DOI Listing
September 2021

Mevalonate Kinase Deficiency: A Cause of Severe Very-Early-Onset Inflammatory Bowel Disease.

Inflamm Bowel Dis 2021 Oct;27(11):1853-1857

Department of Paediatric Immunology, Hematology, and Rheumatology, Groupe Hospitalier Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Reference Centre for Rheumatic, Autoimmune and Systemic Diseases in Children, Assistance Publique-Hôpitaux de Paris, and Imagine Foundation, Paris, France.

Mevalonate kinase deficiency should be considered in patients with severe very-early-onset inflammatory bowel disease (IBD), especially in patients with a history of recurrent or chronic fever, peritoneal adhesions, and atypical IBD pathology. Anti-interleukin-1 therapy may be efficacious in these patients with monogenic very-early-onset IBD.
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http://dx.doi.org/10.1093/ibd/izab139DOI Listing
October 2021

Immunomodulatory treatment and surgical management of idiopathic uveitis and juvenile idiopathic arthritis-associated uveitis in children: a French survey practice.

Pediatr Rheumatol Online J 2021 Sep 3;19(1):139. Epub 2021 Sep 3.

Pediatric diseases and Rheumatology, CHU Bordeaux, Bordeaux, France.

Background: Surgeries for idiopathic uveitis and juvenile idiopathic arthritis-associated uveitis in children are complex because of the high risk of inflammatory postoperative complications. There is no consensus about treatment adaptation during the perioperative period. The objectives of this study are to report the therapeutic changes made in France and to determine whether maintaining or stopping immunosuppressive therapies is associated with an increased risk of surgical site infection or an increased risk of uveitis or arthritis flare-up.

Methods: We conducted a retrospective cohort study between January 1, 2006 and December 31, 2018 in six large University Hospitals in France. Inclusion criteria were chronic idiopathic uveitis or chronic uveitis associated with juvenile idiopathic arthritis under immunosuppressive therapies at the time of the surgical procedure, operated before the age of 16. Data on perioperative treatments, inflammatory relapses and post-operative infections were collected.

Results: A total of 76 surgeries (42% cataract surgeries, 30% glaucoma surgeries and 16% posterior capsule opacification surgeries) were performed on 37 children. Adaptation protocols were different in the six hospitals. Immunosuppressive therapies were discontinued in five cases (7%) before surgery. All the children in the discontinuation group had an inflammatory relapse within 3 months after surgery compared to only 25% in the other group. There were no postoperative infections.

Conclusions: The results of this study show varying practices between centres. The benefit-risk balance seems to favour maintaining immunosuppressive therapies during surgery. Further studies are needed to determine the optimal perioperative treatments required to limit post-operative inflammatory relapses.
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http://dx.doi.org/10.1186/s12969-021-00626-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414774PMC
September 2021

Juvenile Idiopathic Arthritis-Associated Chronic Uveitis: Recent Therapeutic Approaches.

Authors:
Pierre Quartier

J Clin Med 2021 Jun 30;10(13). Epub 2021 Jun 30.

Pediatric Immunology, Hematology and Rheumatology Unit, Necker-Enfants Malades Hospital, Assistance Publique-Hopitaux de Paris, 75015 Paris, France.

Pediatric patients with early onset (before the age of 6 years), antinuclear antibody positive, oligoarticular or polyarticular juvenile idiopathic arthritis (JIA), and some children with no arthritis may develop chronic, anterior uveitis. Recent recommendations insist on the need to perform slit lamp examination every 3 months for at least 5 years in early onset JIA patients in order to diagnose uveitis before complications develop. Local steroid therapy is usually the first-line treatment. However, in patients requiring steroid eye drops for several months, systemic immunomodulatory therapy is indicated. Methotrexate (MTX) is then prescribed in most cases; however, some patients also need anti-tumor necrosis factor alpha monoclonal antibody therapy and, in some cases, other biologics to control uveitis and avoid long-term ocular damage. Expert ophthalmologists and pediatricians must be involved in taking care of such patients. Immunomodulatory treatment must not be too easily interrupted and may even be intensified in some cases, particularly if there is a need for optimal disease control before ophthalmologic surgery. In good responders to MTX and/or biologics, treatment must be maintained at least 1 year, possibly even 2 years after achieving remission before tapering treatment intensity.
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http://dx.doi.org/10.3390/jcm10132934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269439PMC
June 2021

[Professional representation of chronic idiopathic musculoskeletal pain in adolescents].

Soins Pediatr Pueric 2021 May-Jun;42(320):27-30. Epub 2021 Mar 26.

Maison de Solenn - Maison des adolescents de l'hôpital Cochin, AP-HP, 97 boulevard de Port-Royal, 75014 Paris, France; Université Paris-Saclay, UVSQ, Inserm, Centre de recherche en épidémiologie et santé des populations, Team DevPsy, 16 avenue Paul-Vaillant-Couturier, 94807 Villejuif, France.

Chronic idiopathic musculoskeletal pain is common in adolescence, and its impact is sometimes severe. The diagnostic process, which consists of eliminating other etiologies, can be long, complex, and at risk of medical nomadism. Specialists rely on many clinical elements to orient themselves. The care pathway and the subjective feeling of the professional are valuable diagnostic elements.
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http://dx.doi.org/10.1016/j.spp.2021.03.007DOI Listing
June 2021

Sustained remission after haploidentical bone marrow transplantation in a child with refractory systemic juvenile idiopathic arthritis.

Pediatr Rheumatol Online J 2021 Mar 12;19(1):27. Epub 2021 Mar 12.

Pediatric Hematology-Immunology and Rheumatology Department, Necker-Enfants-Malades University Hospital, Assistance Publique Hôpitaux de Paris, 149 rue de Sèvres, 75015, Paris, France.

Background: Some patients with systemic juvenile idiopathic arthritis (SJIA) and severe, refractory disease achieved remission through intensive immunosuppressive treatment followed by autologous hematopoietic stem cell transplantation (HSCT). However, disease relapsed in most cases. More recently selected SJIA patients received allogenic HSCT from a HLA-identical sibling or a HLA matched unrelated donor. While most transplanted patients achieved sustained SJIA remission off-treatment, the procedure-related morbidity was high.

Case Report: A girl presented SJIA with a severe disease course since the age of 15 months. She was refractory to the combination of methotrexate and steroids to anti-interleukin (IL)-1, then anti-IL-6, tumor necrosis factor alpha inhibitors, and thalidomide. Given the high disease burden and important treatment-related toxicity the indication for a haploidentical HSCT from her mother was validated, as no HLA matched donor was available. The patient received a T replete bone marrow graft at the age of 3.7 years. Conditioning regimen contained Rituximab, Alemtuzumab, Busulfan, and Fludarabine. Cyclophosphamide at D + 3 and + 4 post HSCT was used for graft-versus-host-disease prophylaxis, followed by Cyclosporin A and Mycophenolate Mofetil. Post HSCT complications included severe infections, grade 3 intestinal graft-versus-host-disease, autoimmune thyroiditis, and immune thrombocytopenia. Three years after HSCT, the child is alive and well, notwithstanding persistent hypothyroidy requiring substitution. Immune thrombocytopenia had resolved. Most importantly, SJIA was in complete remission, off immunosuppressive drugs.

Conclusion: Allogenic HSCT may be a therapeutic option, even with a HLA haplo-identical alternative donor, in patients with inflammatory diseases such as SJIA. Despite increased experience with this treatment, the risk of life-threatening complications restrains its indication to selected patients with severe, refractory disease.
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http://dx.doi.org/10.1186/s12969-021-00523-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953742PMC
March 2021

JAK inhibitors are effective in a subset of patients with juvenile dermatomyositis: a monocentric retrospective study.

Rheumatology (Oxford) 2021 Feb 12. Epub 2021 Feb 12.

Department of Paediatric Hematology-Immunology and Rheumatology, Necker-Enfants Malades Hospital, AP-HP, Paris, France, Reference center for Rheumatic, AutoImmune and Systemic diseases in children (RAISE), Paris, France.

Objective: To evaluate the efficacy and safety of JAK inhibitors (JAKi) in juvenile dermatomyositis (JDM).

Methods: We conducted a single-center retrospective study of patients with JDM treated by JAKi with a follow-up of at least 6 months. Proportion of clinically inactive disease (CID) within six months of JAKi initiation was evaluated using PRINTO criteria and skin Disease Activity Score. Serum IFN-α concentration was measured by SIMOA assay.

Results: Nine refractory and one new-onset patients with JDM treated with ruxolitinib (n = 7) or baricitinib (n = 3) were included. The main indications for treatment were refractory muscle involvement (n = 8) and ulcerative skin disease (n = 2). CID was achieved in 5/10 patients (2/2 anti-MDA5, 3/4 anti-NXP2, 0/3 anti-TIF1γ positive patients) within six months of JAKi introduction. All responders could withdraw plasmatic exchange, immunoadsorption and other immunosuppressive drugs. The mean daily steroid dose decreased from 1.1 mg/Kg (range 0.35-2 mg/Kg/d) to 0.1 (range, 0-0.3, p= 0.008) in patients achieving CID, and was stopped in two. Serum IFN-α concentrations were elevated in all patients at the time of treatment initiation and normalized in both responder and non-responder. A muscle biopsy repeated in one patient 26 months after the initiation of JAKi, showed a complete restoration of muscle endomysial microvascular bed. Herpes zoster and skin abscesses developed in three and two patients, respectively.

Conclusion: JAKis resulted in a CID in a subset of new-onset or refractory patients with JDM and may dramatically reverse severe muscle vasculopathy. Overall tolerance was good except for a high rate of herpes zoster infection.
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http://dx.doi.org/10.1093/rheumatology/keab116DOI Listing
February 2021

Absence of Association Between Abatacept Exposure and Initial Infection in Patients With Juvenile Idiopathic Arthritis.

J Rheumatol 2021 07 15;48(7):1073-1081. Epub 2021 Jan 15.

A. Martini, MD, IRCCS Istituto G Gaslini, Clinica Pediatrica e Reumatologia, Genoa, Italy and Università di Genova, Genoa, Italy.

Objective: To assess the relationship between infection risk and abatacept (ABA) exposure levels in patients with polyarticular-course juvenile idiopathic arthritis (pJIA) following treatment with subcutaneous (SC) and intravenous (IV) ABA.

Methods: Data from 2 published studies (ClinicalTrials.gov: NCT01844518, NCT00095173) of ABA treatment in pediatric patients were analyzed. One study treated patients aged 2-17 years with SC ABA and the other treated patients aged 6-17 years with IV ABA. Association between serum ABA exposure measures and infection was evaluated using Kaplan-Meier plots of probability of first infection vs time on treatment by ABA exposure quartiles and log-rank tests. Number of infections by ABA exposure quartiles was investigated.

Results: Overall, 343 patients were included in this analysis: 219 patients received SC ABA and 124 patients received IV ABA. Overall, 237/343 (69.1%) patients had ≥ 1 infection over 24 months. No significant difference in time to first infection across 4 quartiles of ABA exposure levels was observed in the pooled ( = 0.45), SC (2-5 yrs: = 0.93; 6-17 yrs: = 0.48), or IV ( = 0.50) analyses. Concomitant use of methotrexate and glucocorticoids (at baseline and throughout) with ABA did not increase infection risk across the ABA exposure quartiles. There was no evidence of association between number of infections and ABA exposure quartiles. No opportunistic infections related to ABA were reported.

Conclusion: In patients aged 2-17 years with pJIA, no evidence of association between higher levels of exposure to IV ABA or SC ABA and incidence of infection was observed.
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http://dx.doi.org/10.3899/jrheum.200154DOI Listing
July 2021

Differential Expression of Interferon-Alpha Protein Provides Clues to Tissue Specificity Across Type I Interferonopathies.

J Clin Immunol 2021 04 7;41(3):603-609. Epub 2021 Jan 7.

General Paediatrics- Infectious Diseases and Internal Medicine Department, Robert-Debré Hospital, AP-HP, Nord - Université de Paris, Paris, France.

Whilst upregulation of type I interferon (IFN) signaling is common across the type I interferonopathies (T1Is), central nervous system (CNS) involvement varies between these disorders, the basis of which remains unclear. We collected cerebrospinal fluid (CSF) and serum from patients with Aicardi-Goutières syndrome (AGS), STING-associated vasculopathy with onset in infancy (SAVI), presumed monogenic T1Is (pT1I), childhood systemic lupus erythematosus with neuropsychiatric features (nSLE), non-IFN-related autoinflammation (AI) and non-inflammatory hydrocephalus (as controls). We measured IFN-alpha protein using digital ELISA. Eighty-two and 63 measurements were recorded respectively in CSF and serum of 42 patients and 6 controls. In an intergroup comparison (taking one sample per individual), median CSF IFN-alpha levels were elevated in AGS, SAVI, pT1I, and nSLE compared to AI and controls, with levels highest in AGS compared to all other groups. In AGS, CSF IFN-alpha concentrations were higher than in paired serum samples. In contrast, serum IFN was consistently higher compared to CSF levels in SAVI, pT1I, and nSLE. Whilst IFN-alpha is present in the CSF and serum of all IFN-related diseases studied here, our data suggest the primary sites of IFN production in the monogenic T1I AGS and SAVI are, respectively, the CNS and the periphery. These results inform the diagnosis of, and future therapeutic approaches to, monogenic and multifactorial T1Is.
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http://dx.doi.org/10.1007/s10875-020-00952-xDOI Listing
April 2021

From Diagnosis to Prognosis: Revisiting the Meaning of Muscle ISG15 Overexpression in Juvenile Inflammatory Myopathies.

Arthritis Rheumatol 2021 06 26;73(6):1044-1052. Epub 2021 Apr 26.

Institut Mondor de Recherche Biomédicale, Université Paris-Est Créteil, INSERM, Centre de Reference pour les Maladies Neuromusculaires, Hôpital Necker-Enfants Malades, AP-HP, FILNEMUS, Paris, France.

Objective: Juvenile idiopathic inflammatory/immune myopathies (IIMs) constitute a highly heterogeneous group of disorders with diagnostic difficulties and prognostic uncertainties. Circulating myositis-specific autoantibodies (MSAs) have been recognized as reliable tools for patient substratification. Considering the key role of type I interferon (IFN) up-regulation in juvenile IIM, we undertook the present study to investigate whether IFN-induced 15-kd protein (ISG-15) could be a reliable biomarker for stratification and diagnosis and to better elucidate its role in juvenile IIM pathophysiology.

Methods: The study included 56 patients: 24 with juvenile dermatomyositis (DM), 12 with juvenile overlap myositis (OM), 10 with Duchenne muscular dystrophy, and 10 with congenital myopathies. Muscle biopsy samples were assessed by immunohistochemistry, immunoblotting, and real-time quantitative polymerase chain reaction. Negative regulators of type I IFN (ISG15 and USP18) and positive regulators of type I IFN (DDX58 and IFIH1) were analyzed.

Results: ISG15 expression discriminated patients with juvenile IIM from those with nonimmune myopathies and, among patients with juvenile IIM, discriminated those with DM from those with OM. Among patients with juvenile DM, up-regulation of the type I IFN positive regulators DDX58 and IFIH1 was similar regardless of MSA status. In contrast, the highest levels of the type I IFN negative regulator ISG15 were observed in patients who were positive for melanoma differentiation-associated gene 5 (MDA-5). Finally, ISG15 levels were inversely correlated with the severity of muscle histologic abnormalities and positively correlated with motor performance as evaluated by the Childhood Myositis Assessment Scale and by manual muscle strength testing.

Conclusion: Muscle ISG15 expression is strongly associated with juvenile DM, with patients exhibiting a different ISG-15 muscle signature according to their MSA class. Patients with juvenile DM who are positive for MDA-5 have higher expression of ISG15 in both gene form and protein form compared to the other subgroups. Moreover, our data show that negative regulation of type I IFN correlates with milder muscle involvement.
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http://dx.doi.org/10.1002/art.41625DOI Listing
June 2021

Development and Testing of Reduced Versions of the Manual Muscle Test-8 in Juvenile Dermatomyositis.

J Rheumatol 2021 06 15;48(6):898-906. Epub 2020 Nov 15.

C. Malattia, MD, PhD, A. Consolaro, MD, PhD, UOC Clinica Pediatrica e Reumatologia, IRCCS Istituto Giannina Gaslini and Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili (DiNOGMI), Università degli Studi di Genova, Genoa, Italy.

Objective: To develop and test shortened versions of the Manual Muscle Test-8 (MMT-8) in juvenile dermatomyositis (JDM).

Methods: Construction of reduced tools was based on a retrospective analysis of individual scores of MMT-8 muscle groups in 3 multinational datasets. The 4 and 6 most frequently impaired muscle groups were included in MMT-4 and MMT-6, respectively. Metrologic properties of reduced tools were assessed by evaluating construct validity, internal consistency, discriminant ability, and responsiveness to change.

Results: Neck flexors, hip extensors, hip abductors, and shoulder abductors were included in MMT-4, whereas MMT-6 also included elbow flexors and hip flexors. Both shortened tools revealed strong correlations with MMT-8 and other muscle strength measures. Correlations with other JDM outcome measures were in line with predictions. Internal consistency was good (0.88-0.96) for both MMT-4 and MMT-6. Both reduced tools showed strong ability to discriminate between disease activity states, assessed by the caring physician or a parent ( < 0.001), and between patients whose parents were satisfied or not satisfied with illness course ( < 0.001). Responsiveness to change (assessed by both standardized response mean and relative efficiency) of MMT-4 and, to a lesser degree, MMT-6, was slightly superior to that of MMT-8.

Conclusion: Overall, the metrologic performance of MMT-4 and MMT-6 was comparable to that of the other established muscle strength tools, which indicates that they may be suitable for use in clinical practice and research, including clinical trials. The measurement properties of these tools should be further tested in other patient populations and evaluated prospectively.
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http://dx.doi.org/10.3899/jrheum.200543DOI Listing
June 2021

Burden of illness in hereditary periodic fevers: a multinational observational patient diary study.

Clin Exp Rheumatol 2020 Sep-Oct;38 Suppl 127(5):26-34. Epub 2020 Sep 30.

Medicine F, Sheba Medical Centre, Tel-Hashomer, Ramat-Gan, Israel.

Objectives: This study aimed to characterise the burden of illness of patients with inadequately controlled hereditary periodic fevers (HPFs), during and outside of flares. It was focused on the burden to the patients and also considered the wider impact on their caregivers and families.

Methods: The target population was patients or caregivers of patients with clinically/genetically confirmed colchicine resistant FMF (crFMF), mevalonate kinase deficiency/hyperimmunoglobinaemia D with periodic fever syndrome (MKD/HIDS) or TRAPS, who were expected to flare at least once in a 6-month period based on patient history. Disease burden was captured during and between flares using an electronic diary (e-diary) with questions on patient functioning, emotional/social well-being and pain, using validated instruments.

Results: HPF-related symptoms such as fever, joint, muscle or bone pain and tiredness and fatigue were reported by patients both during and outside of a flare. The SF-10 Health Survey (SF-10v2) (paediatric patients) and SF-12 Health Survey (SF-12v2) (adult patients) showed that flares negatively impacted patients' psychosocial and physical health. Negative effect of on-flare status on health utility index score assessed by the Short-Form Six-Dimension (SF-6D) was significant only for crFMF patients. Furthermore, the Sheehan Disability Score (SDSv3) showing the on-flare status resulted in significant functional impairment in all 3 disease cohorts through assessment of impact on work/school, social and family life.

Conclusions: crFMF, MKD/HIDS and TRAPS negatively affected the quality of life (QoL) of adult and paediatric patients, including their physical, mental, psychosocial health, and social functioning. There remains, however, a high number of unmet needs for these patients to reduce their disease burden.
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December 2020

Laser Flare Photometry: A Useful Tool for Monitoring Patients with Juvenile Idiopathic Arthritis-associated Uveitis.

Ocul Immunol Inflamm 2020 Aug 24:1-11. Epub 2020 Aug 24.

Department of Ophthalmology, La Pitié-Salpétrière Hospital, DHU View Restore, Paris, France.

Purpose: We evaluated laser flare photometry (LFP) values in patients with juvenile idiopathic arthritis (JIA)-associated uveitis.

Methods: Retrospective study. A decrease of the LFP value between baseline visit and 1 month after anti-inflammatory treatment intensification allowed us to define two groups of patients: group 1 (decreased LFP value ≥50%) and group 2 (<50%). We evaluated the prevalence of vision-threatening complications in both groups.

Results: Fifty-four patients (87 eyes) were followed for 9.9 ± 5 years. Group 1 eyes (n = 54) had significantly fewer ocular complications than group 2 eyes (n = 33) at both 5 years visit ( = .03) and final visit ( = .047). At the final visit, group 2 eyes had significantly more band keratopathy, trabeculectomy, cataract surgery, glaucoma and papille edema. Group 1 eyes kept a better visual acuity ( < .0001).

Conclusion: The decrease of LFP values ≥50% of the initial value 1 month after treatment intensification is a good early prognostic factor.
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http://dx.doi.org/10.1080/09273948.2020.1792511DOI Listing
August 2020

Tapering Canakinumab Monotherapy in Patients With Systemic Juvenile Idiopathic Arthritis in Clinical Remission: Results From a Phase IIIb/IV Open-Label, Randomized Study.

Arthritis Rheumatol 2021 02 11;73(2):336-346. Epub 2020 Dec 11.

Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, United States.

Objective: To evaluate the efficacy and safety of 2 canakinumab monotherapy tapering regimens in order to maintain complete clinical remission in children with systemic juvenile idiopathic arthritis (JIA).

Methods: The study was designed as a 2-part phase IIIb/IV open-label, randomized trial. In the first part, patients received 4 mg/kg of canakinumab subcutaneously every 4 weeks and discontinued glucocorticoids and/or methotrexate as appropriate. Patients in whom clinical remission was achieved (inactive disease for at least 24 weeks) with canakinumab monotherapy were entered into the second part of the trial, in which they were randomized 1:1 into 1 of 2 treatment arms. In arm 1, the dose of canakinumab was reduced from 4 mg/kg to 2 mg/kg and then to 1 mg/kg, followed by discontinuation. In arm 2, the 4 mg/kg dose interval was prolonged from every 4 weeks, to every 8 weeks, and then to every 12 weeks, followed by discontinuation. In both arms, canakinumab exposure could be reduced provided systemic JIA remained in clinical remission for 24 weeks with each step. The primary objective was to assess whether >40% of randomized patients in either arm maintained clinical remission of systemic JIA for 24 weeks in the first part of the study.

Results: In part 1 of the study, 182 patients were enrolled, with 75 of those patients randomized before entering part 2 of the trial. Among the 75 randomized patients, clinical remission was maintained for 24 weeks in 27 (71%) of 38 patients in arm 1 (2 mg/kg every 4 weeks) and 31 (84%) of 37 patients in arm 2 (4 mg/kg every 8 weeks) (P ≤ 0.0001 for arm 1 versus arm 2 among those meeting the 40% threshold). Overall, 25 (33%) of 75 patients discontinued canakinumab, and clinical remission was maintained for at least 24 weeks in all 25 of these patients. No new safety signals were identified.

Conclusion: Reduction of canakinumab exposure may be feasible in patients who have achieved clinical remission of systemic JIA, but consistent interleukin-1 inhibition appears necessary to maintain this response.
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http://dx.doi.org/10.1002/art.41488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898684PMC
February 2021

Efficacy and Safety of Canakinumab in Patients With Systemic Juvenile Idiopathic Arthritis With and Without Fever at Baseline: Results From an Open-Label, Active-Treatment Extension Study.

Arthritis Rheumatol 2020 12 31;72(12):2147-2158. Epub 2020 Oct 31.

IRCCS, Istituto Giannina Gaslini, Clinica Pediatrica e Reumatologia, PRINTO, Genoa, Italy.

Objective: To evaluate the long-term efficacy and safety of canakinumab and explore prediction of response in patients with systemic juvenile idiopathic arthritis (JIA) with or without fever at treatment initiation.

Methods: At enrollment, patients with active systemic JIA (ages 2 to <20 years) started open-label canakinumab (4 mg/kg every 4 weeks subcutaneously). Efficacy measures included the adapted American College of Rheumatology (ACR) Pediatric 50/70/90 criteria, the Juvenile Arthritis Disease Activity Score (JADAS), and clinically inactive disease and clinical remission on medication, evaluated by either the JADAS or ACR criteria.

Results: Of the 123 patients (70 with fever and 52 without fever [fever status was not reported for 1 patient]), 84 (68.3%) completed the study (median duration 1.8 years). Comparable efficacy (adapted ACR Pediatric 50/70/90/100) was observed by day 15 in both subgroups (60.0%/48.6%/37.1%/24.3% in those with fever and 67.3%/48.1%/34.6%/19.2% in those without fever), and further increased thereafter. By month 6, clinical remission according to the JADAS or the ACR criteria was achieved in 17 (24.3%) and 26 (37.1%), respectively, of patients with fever and 9 (17.3%) and 12 (23.1%), respectively, of patients without fever. Median time to onset of clinical remission according to the JADAS or ACR criteria was 57 and 30 days, respectively, in those with fever, and 58 and 142 days, respectively, in those without fever. An adapted ACR Pediatric 50 response by day 15 was the strongest predictor of achieving clinical remission according to the JADAS (odds ratio [OR] 13 [95% confidence interval (95% CI) 4, 42]; P < 0.0001) or glucocorticoid discontinuation (OR 19 [95% CI 3, 114]; P = 0.002). Of the 71 of 123 patients (57.7%) who received glucocorticoids at study entry, 27 (38.0%) discontinued glucocorticoids and 21 (29.6%) reached a dose of <0.2 mg/kg/day, with no difference between those with and those without fever; 13 patients (10.6%) tolerated a sustained canakinumab dose reduction to 2 mg/kg every 4 weeks. No new safety findings were observed.

Conclusion: Canakinumab provided rapid and sustained improvement of active systemic JIA irrespective of the presence of fever at treatment initiation.
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http://dx.doi.org/10.1002/art.41436DOI Listing
December 2020

Inflammatory Bowel Disease in Children With Systemic Juvenile Idiopathic Arthritis.

J Rheumatol 2021 04 15;48(4):567-574. Epub 2020 Jun 15.

E.D. Mellins, MD, Department of Pediatrics, Division of Human Gene Therapy, Program in Immunology, Stanford University School of Medicine, Stanford, California, USA.

Objective: The incidence of inflammatory bowel disease (IBD) in juvenile idiopathic arthritis (JIA) is higher than in the general pediatric population. However, reports of IBD in the systemic JIA (sJIA) subtype are limited. We sought to characterize sJIA patients diagnosed with IBD and to identify potential contributing risk factors.

Methods: Using an internationally distributed survey, we identified 16 patients with sJIA who were subsequently diagnosed with IBD (sJIA-IBD cohort). Five hundred twenty-two sJIA patients without IBD were identified from the CARRA Legacy Registry and served as the sJIA-only cohort for comparison. Differences in demographic, clinical characteristics, and therapy were assessed using chi-square test, Fisher exact test, -test, and univariate and multivariate logistic regression, as appropriate.

Results: Of the patients with sJIA-IBD, 75% had a persistent sJIA course and 25% had a history of macrophage activation syndrome. sJIA-IBD subjects were older at sJIA diagnosis, more often non-White, had a higher rate of IBD family history, and were more frequently treated with etanercept or canakinumab compared to sJIA-only subjects. Sixty-nine percent of sJIA-IBD patients successfully discontinued sJIA medications following IBD diagnosis, and sJIA symptoms resolved in 9 of 12 patients treated with tumor necrosis factor-α (TNF-α) inhibitors.

Conclusion: IBD in the setting of sJIA is a rare occurrence. The favorable response of sJIA symptoms to therapeutic TNF-α inhibition suggests that the sJIA-IBD cohort may represent a mechanistically distinct sJIA subgroup. Our study highlights the importance of maintaining a high level of suspicion for IBD when gastrointestinal involvement occurs in patients with sJIA and the likely broad benefit of TNF-α inhibition in those cases.
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http://dx.doi.org/10.3899/jrheum.200230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736056PMC
April 2021

Serious adverse events in children with juvenile idiopathic arthritis and other rheumatic diseases on tocilizumab - a real-world experience.

Semin Arthritis Rheum 2020 08 30;50(4):744-748. Epub 2020 May 30.

IMAGINE Institute, RAISE reference center for rare diseases, Department of Pediatric Immunology, Hematology and Rheumatology, Necker Hospital, AP-HP, Paris, France; Paris University, Paris, France. Electronic address:

Objectives: To assess the incidence rate and type of serious adverse events (SAE) in children with rheumatic inflammatory diseases treated with the interleukin 6 blocker tocilizumab (TCZ).

Methods: A retrospective review of all consecutive patients diagnosed with an inflammatory rheumatic disease and receiving at least one dose of TCZ was performed in two French tertiary pediatric rheumatology centers between 01/2007 and 06/2019. SAE were defined as a life-threatening event and/or an event requiring hospital admission, leading to permanent disability or treatment discontinuation.

Results: One hundred four children (64 female) were included. Most children suffered from systemic (n = 43) or polyarticular-course juvenile idiopathic arthritis (n = 43). Median age at TCZ start was 8.9 years (IQR 4.7 - 12.1), most children had received prednisone (81%), and/or a biologic agent (84%) prior to TCZ. Median TCZ treatment duration was 1.6 years (IQR 0.5 - 2.7), total TCZ exposure 215 patient years. Thirty-three SAE were observed in 26 (25%) children (SAE 15.3/100 patient years), mostly infections and infusion reactions. Children with SAE were significantly younger at disease onset (p = 0.034) and TCZ initiation (p = 0.016). Children experiencing infusion reactions were more likely to have systemic JIA or another autoinflammatory disease (p = 0.021), they all had active disease. At last follow up, 61 (59%) children remained on TCZ.

Conclusion: In this cohort, SAE and most commonly serious infections were observed in a quarter of children. Severe infusion reactions were associated with persistently active autoinflammatory disease. Ongoing careful monitoring of TCZ-treated patients, especially young children with marked systemic inflammation is required.
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http://dx.doi.org/10.1016/j.semarthrit.2020.05.013DOI Listing
August 2020

Acute myocarditis and multisystem inflammatory emerging disease following SARS-CoV-2 infection in critically ill children.

Ann Intensive Care 2020 Jun 1;10(1):69. Epub 2020 Jun 1.

Pediatric Intensive Care Unit, Necker-Enfants-Malades University Hospital, Assistance Publique-Hôpitaux de Paris, Paris University, EA7323, 75006, Paris, France.

Background: A recent increase in children admitted with hypotensive shock and fever in the context of the COVID-19 outbreak requires an urgent characterization and assessment of the involvement of SARS-CoV-2 infection. This is a case series performed at 4 academic tertiary care centers in Paris of all the children admitted to the pediatric intensive care unit (PICU) with shock, fever and suspected SARS-CoV-2 infection between April 15th and April 27th, 2020.

Results: 20 critically ill children admitted for shock had an acute myocarditis (left ventricular ejection fraction, 35% (25-55); troponin, 269 ng/mL (31-4607)), and arterial hypotension with mainly vasoplegic clinical presentation. The first symptoms before PICU admission were intense abdominal pain and fever for 6 days (1-10). All children had highly elevated C-reactive protein (> 94 mg/L) and procalcitonin (> 1.6 ng/mL) without microbial cause. At least one feature of Kawasaki disease was found in all children (fever, n = 20, skin rash, n = 10; conjunctivitis, n = 6; cheilitis, n = 5; adenitis, n = 2), but none had the typical form. SARS-CoV-2 PCR and serology were positive for 10 and 15 children, respectively. One child had both negative SARS-CoV-2 PCR and serology, but had a typical SARS-CoV-2 chest tomography scan. All children but one needed an inotropic/vasoactive drug support (epinephrine, n = 12; milrinone, n = 10; dobutamine, n = 6, norepinephrine, n = 4) and 8 were intubated. All children received intravenous immunoglobulin (2 g per kilogram) with adjuvant corticosteroids (n = 2), IL 1 receptor antagonist (n = 1) or a monoclonal antibody against IL-6 receptor (n = 1). All children survived and were afebrile with a full left ventricular function recovery at PICU discharge.

Conclusions: Acute myocarditis with intense systemic inflammation and atypical Kawasaki disease is an emerging severe pediatric disease following SARS-CoV-2 infection. Early recognition of this disease is needed and referral to an expert center is recommended. A delayed and inappropriate host immunological response is suspected. While underlying mechanisms remain unclear, further investigations are required to target an optimal treatment.
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http://dx.doi.org/10.1186/s13613-020-00690-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266128PMC
June 2020

Maintenance of antibody response to diphtheria/tetanus vaccine in patients aged 2-5 years with polyarticular-course juvenile idiopathic arthritis receiving subcutaneous abatacept.

Pediatr Rheumatol Online J 2020 Feb 22;18(1):19. Epub 2020 Feb 22.

Istituto Giannina Gaslini, Genoa, Italy.

Background: Patients with polyarticular-course juvenile idiopathic arthritis (pJIA), receiving disease-modifying anti-rheumatic drugs with immunosuppressive effects, may be at increased risk of vaccine-preventable infections. This substudy assessed protective antibody responses to diphtheria and tetanus vaccination given prior to study enrolment in patients with pJIA.

Findings: This was a substudy of a 24-month, single-arm, open-label, multicenter, Phase III trial (NCT01844518) of subcutaneous abatacept in children with active pJIA (N = 219). Patients aged 2-5 years, with ≥2 continuous months of weekly weight-tiered (10-< 25 kg [50 mg], 25-< 50 kg [87.5 mg]) subcutaneous abatacept treatment (with/without methotrexate and/or low-dose corticosteroids), who received diphtheria/tetanus vaccine prior to enrolment, were eligible. Protective antibody levels to diphtheria/tetanus (> 0.1 IU/mL), and safety, were assessed. Overall, 29 patients were analyzed: 19 (65.5%), 1 (3.4%) and 9 (31.0%) patients had > 12, 6-12 and 2-< 6 months of abatacept exposure, respectively. All patients had protective antibody levels to tetanus and 26 (89.7%) patients had protective antibody levels to diphtheria. Of the 3 patients without protective antibody levels to diphtheria, each had an antibody level of 0.1 IU/mL, bordering the lower threshold of protection. Concomitant use of methotrexate and/or low-dose corticosteroids had no evident effect on antibody levels. No unexpected adverse events, including cases of diphtheria or tetanus, were reported during the 24-month period.

Conclusions: Patients aged 2-5 years with pJIA who received 2-24 months of weekly subcutaneous abatacept, with or without concomitant methotrexate and/or low-dose corticosteroids, maintained effective diphtheria and tetanus vaccination protection without new safety signals.

Trial Registration: ClinicalTrials.gov (NCT01844518); registered May 1, 2013; https://clinicaltrials.gov/ct2/show/NCT01844518?term=NCT01844518&rank=1.
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http://dx.doi.org/10.1186/s12969-020-0410-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7036185PMC
February 2020

Severe Abdominal Manifestations in Juvenile Dermatomyositis.

J Pediatr Gastroenterol Nutr 2020 02;70(2):247-251

Laboratoire d'Immunogénétique des maladies auto-immunes de l'enfant, Institut Imagine, INSERM U 1163.

Juvenile dermatomyositis (JDM) is a rare and heterogeneous pediatric-onset idiopathic inflammatory myopathy. Gastrointestinal (GI) involvement occurs in 22% to 37% of JDM patients but has only been described in case reports. In this retrospective, single-center, observational study, we aimed to assess the causes and management of severe GI manifestations in JDM patients. We studied a cohort of 9 patients among 110 JDM patients followed during the study period (8.3%). The GI complications were related to JDM in most cases (17/19), with digestive tract involvement (n = 10), acute pancreatitis (n = 4), and hepatitis (n = 3). Three patients died from refractory JDM 2.9 years (2-3.6) after the JDM diagnosis. We highlight the need to consider pancreatitis as a main diagnostic factor in JDM patients with severe GI manifestations and the requirement of early aggressive treatment for these patients.
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http://dx.doi.org/10.1097/MPG.0000000000002575DOI Listing
February 2020

Do we need the PFAPA syndrome in adults with non-monogenic periodic fevers?

Ann Rheum Dis 2019 Dec 31. Epub 2019 Dec 31.

Service de médecine interne, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, Paris, France.

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http://dx.doi.org/10.1136/annrheumdis-2019-216827DOI Listing
December 2019

Chronic idiopathic musculoskeletal pain in youth: a qualitative study.

Pediatr Rheumatol Online J 2019 Dec 27;17(1):86. Epub 2019 Dec 27.

AP-HP, Cochin Hospital, Maison de Solenn, Paris, France.

Background: Chronic musculoskeletal pain (MSP) is frequent in adolescents and has major medical and social consequences. In many cases, when no cause has been clearly established, this pain may be considered to be chronic idiopathic MSP. Our study seeks to identify general criteria for this type of pain through the experience of professionals from tertiary care centers with expertise in pediatric and adolescent chronic MSP.

Methods: Cross-sectional multicenter qualitative study. Semi-structured interviews of 25 professionals at a rheumatology reference center and in its network for pain management, including diverse specialists and professions. Interpretative Phenomenological Analysis is used to explore the data.

Results: This approach led us to identify 10 themes organized around three superordinate themes covering different stages of the diagnostic process: 1) the medical pain history up to the consultation at the reference center; 2) the professional's subjective feelings about the clinical presentation; 3) from the clinical examination to diagnosis and treatment of chronic idiopathic MSP. The main elements guiding this diagnosis do not come from the physical examination but from the medical history and the professionals' subjective feelings, that is, their clinical judgment. The professionals' impression of uneasiness and frustration, induced by patients and their parents, is of major importance.

Conclusion: The principal elements guiding the diagnosis of chronic idiopathic MSP do not come primarily from the physical examination but rather from the pain history and the health professional's subjective feelings. Our results suggest that the concept of Juvenile Fibromyalgia (JFM) does not appear to cover all situations of chronic idiopathic MSP in adolescence. A constellation of non-organic criteria enables diagnosis of the latter; these criteria should be validated to avoid medical nomadism and multiple investigations and to shorten the interval until patients receive optimal pain management.

Clinical Trial Registration: clinicaltrials.gov, NCT03171792, https://clinicaltrials.gov/ct2/show/NCT03171792?term=LACHAL&cntry=FR&city=paris&rank=1.
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http://dx.doi.org/10.1186/s12969-019-0389-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935211PMC
December 2019

Anakinra in children and adults with Still's disease.

Rheumatology (Oxford) 2019 11;58(Suppl 6):vi9-vi22

Division of Rheumatology, Ospedale Pediatrico Bambino Gesù, Rome, Italy.

Systemic juvenile idiopathic arthritis and adult-onset Still's disease are rare autoinflammatory disorders with common features, supporting the recognition of these being one disease-Still's disease-with different ages of onset. Anakinra was recently approved by the European Medicines Agency for Still's disease. In this review we discuss the reasoning for considering Still's disease as one disease and present anakinra efficacy and safety based on the available literature. The analysis of 27 studies showed that response to anakinra in Still's disease was remarkable, with clinically inactive disease or the equivalent reported for 23-100% of patients. Glucocorticoid reduction and/or stoppage was reported universally across the studies. In studies on paediatric patients where anakinra was used early or as first-line treatment, clinically inactive disease and successful anakinra tapering/stopping occurred in >50% of patients. Overall, current data support targeted therapy with anakinra in Still's disease since it improves clinical outcome, especially if initiated early in the disease course.
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http://dx.doi.org/10.1093/rheumatology/kez350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6878842PMC
November 2019

Anti-MDA5 juvenile idiopathic inflammatory myopathy: a specific subgroup defined by differentially enhanced interferon-α signalling.

Rheumatology (Oxford) 2020 08;59(8):1927-1937

Laboratory of Neurogenetics and Neuroinflammation, Imagine Institute, Paris.

Objectives: JDM and juvenile overlap myositis represent heterogeneous subtypes of juvenile idiopathic inflammatory myopathy (JIIM). Chronic evolution can occur in up to 60% of cases, and morbidity/mortality is substantial. We aimed to describe the clinical, biological, histological and type I IFN status in JIIM associated with anti-melanoma differentiation-associated protein 5 (anti-MDA5) autoantibodies at presentation (group 1) in comparison with other JIIM (group 2).

Methods: This was a retrospective and prospective study of patients with JIIM ascertained from three French paediatric rheumatology reference centres between 2013 and 2019. Muscle biopsies were reviewed. Type I interferon pathway activity was assessed by dosage of IFNα serum protein and the expression of IFN-stimulated genes.

Results: Sixty-four patients were included, 13 in group 1 (54% JDM and 46% juvenile overlap myositis) and 51 in group 2 (76% JDM and 24% juvenile overlap myositis). Group 1 patients demonstrated more arthritis, skin ulcerations, lupus features and interstitial lung disease, and a milder muscular involvement. Serum IFNα levels were higher in group 1 than 2, and decreased after treatment or improvement in both groups. Outcome was similar in both groups. Unconventional treatment (more than two lines) was required in order to achieve remission, especially when skin ulceration was reported.

Conclusion: This study indicates a higher frequency of arthritis, skin ulcerations and interstitial lung disease, but milder muscular involvement, in JIIM with positive anti-MDA5 autoantibodies compared with other JIIM. Our data support an important role of systemic IFNα in disease pathology, particularly in the anti-MDA5 auto-antibody-positive subgroup. In severe and refractory forms of JIIM, IFNα may represent a therapeutic target.
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http://dx.doi.org/10.1093/rheumatology/kez525DOI Listing
August 2020

Comment on: Monogenic mimics of Behçet's disease in the young.

Rheumatology (Oxford) 2020 11;59(11):e109-e111

Department of Paediatric Immunology-Haematology and Rheumatology, Necker University Hospital - AP-HP.

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http://dx.doi.org/10.1093/rheumatology/kez543DOI Listing
November 2020

Chronic and recurrent non-infectious paediatric-onset uveitis: a French cohort.

RMD Open 2019 5;5(2):e000933. Epub 2019 Aug 5.

RAISE reference centre for rare diseases, IMAGINE Institute, Immunologie, Hématologie et Rhumatologie Pédiatrique, Hopital universitaire Necker-Enfants malades, Assistance Publique Hopitaux de Paris, Paris, France.

Objective: To evaluate the demographics, aetiologies, complications, treatments and visual prognoses of chronic and recurrent non-infectious paediatric-onset uveitis in France.

Methods: Descriptive, retrospective and bicentric study in patients whose disease started before 17 and who were followed up in two centres from January 2010 to May 2017.

Results: We included 147 patients with 268 affected eyes. Eighty-two had juvenile idiopathic arthritis-associated chronic uveitis, 58 were antinuclear antibody (ANA) positive and 24 were ANA negative, 36 had idiopathic uveitis, 9 had enthesitis-related arthritis-associated uveitis, 9 had sarcoidosis-associated uveitis and 11 had other inflammatory aetiologies. These patients cumulated 161 complications: ocular hypertension, cataract, band keratopathy, macular oedema, optic disk oedema and decreased visual acuity, including permanent visual loss for 31 patients. The most used treatments were corticosteroid (CS) eye drops (82%), systemic CSs (34%), methotrexate (58%) and biologics (38%). At the latest follow-up, 45 patients had achieved remission of uveitis without any treatment, 56 had inactive uveitis on topical steroids and 48 still had active uveitis.

Conclusion: Paediatric-onset uveitis are associated with a high rate of complications. However, following the introduction of biologics and particularly antitumour necrosis factor alpha antibodies, a significant proportion of uveitis became inactive on or even off treatment.
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http://dx.doi.org/10.1136/rmdopen-2019-000933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691513PMC
April 2020
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