Autologous haematopoietic stem cell transplantation for systemic scleroderma, developed over more than 25 years, has shown in three randomised controlled clinical trials a significant impact not only ...in event-free survival, overall survival, cutaneous and pulmonary involvement, but also in the quality of life of patients living with recent severe diffuse cutaneous systemic scleroderma, compared with IV cyclophosphamid despite a transplant-related mortality between 2.4 and 10%. No immunosuppressants or biologics have shown such an impact on mortality in this disease. The risk of relapse is estimated between 9 and 24%, two years after transplant. On the basis of these results, French and international guidelines now position autologous haematopoietic stem cell transplantation as a level 1A evidence-based therapeutic alternative in severe early and rapidly progressive systemic scleroderma.
French health insurance databases are organized since 2003 into a huge digital data warehouse, the Système national d’information inter-régime de l’assurance maladie (SNIIR-AM). It covers the entire ...French population (65 million inhabitants). In order to facilitate studies on more frequent conditions, a random sample of 1/97th of national health system beneficiaries has been built since 2005, called the échantillon généraliste des bénéficiaires (EGB). The aim of this article is to describe the main characteristics of the SNIIR-AM and the EGB, to detail their accessibility according to French law, and to present their strengths and limits. It is illustrated with the most recent studies conducted in these databases. These databases include demographic, out-hospital reimbursement (including drug dispensing), medical (costly long-term diseases, occupational diseases, sick-leaves…), and in-hospital data. All these data are prospectively recorded, individualized, made anonymous and linkable. Consequently, the SNIIR-AM is a very useful data source for epidemiological, pharmacoepidemiological and health economics studies, particularly for rare diseases. The EGB is appropriate for long-term research on more frequent diseases.
Les bases de données de l’assurance maladie sont collectées depuis 2003 dans un vaste entrepôt numérique, le Système national d’information inter-régime de l’assurance maladie (SNIIR-AM). La résultante en est une des plus grandes bases médico-administratives au monde, couvrant 65 millions de personnes. Afin de faciliter l’étude de cohortes de patients atteints de maladies plus fréquentes, un échantillon au 1/97e des assurés à l’assurance maladie a été constitué depuis 2005 : l’échantillon généraliste des bénéficiaires (EGB). L’objectif de cette mise au point est de présenter les grandes lignes de l’architecture du SNIIR-AM et de l’EGB, leurs modalités d’accès, leurs intérêts et leurs limites. Leur potentiel en recherche médicale est illustré par les publications les plus récentes. Ces bases de données contiennent des données démographiques, les données de remboursements des prestations ambulatoires (dont les délivrances de médicaments), les données médicales des régimes de l’assurance maladie (affections de longue durée, maladies professionnelles, arrêts de travail…) et les données hospitalières issues du programme de médicalisation des systèmes d’information. Toutes ces données sont individuelles, prospectivement recueillies, anonymisées et chaînables. Tout cela fait du SNIIR-AM une source de données très intéressante pour la recherche épidémiologique, pharmacoépidémiologique et en économie de la santé, particulièrement pour les maladies rares. L’EGB est particulièrement utile à l’étude des maladies plus fréquentes et sur le long terme.
Idiopathic inflammatory myopathies (IIM) diagnosis and sub-classification can be improved by detection of myositis specific antibodies (MSA) as a first step in diagnosis. However, when using ...semi-quantitative immunodots for MSA detection, clinical assay performance needs to be improved.
A retrospective study was done for the “myositis” and “synthetase” immunodots (SRP, NXP2, TIF1gamma, SAE1/2, Mi2, MDA5, Jo1, PL7, PL12, EJ, OJ, KS, ZO and HA) from D-Tek used for 270 patients who had tested positive for MSA in a tertiary laboratory hospital.
Results from this analysis revealed: (i) none of the 60 healthy controls presented MSA; (ii) a low assay specificity among patients who tested positive for MSA, 128/270 (47%) were labeled IIM based on the manufacturer's recommended threshold; (iii) in non-IIM patients (53%), the MSA spectrum overlaps predominantly with other autoimmune diseases or idiopathic interstitial lung disease; and (iv) use of a clinical cut-off improves assay specificity for anti-SRP, anti-NXP2, anti-MDA5, anti-Jo1 and anti-PL7 Abs.
Determining the clinical threshold of the semi-quantitative immunodot assay for MSA is effective for improving its capacity to discriminate IIM from non-IIM and, when IIM diagnosis is excluded, another autoimmune disease or an idiopathic interstitial lung disease should be considered in front of a positive MSA.
The aim of our study was to assess major cardiovascular event incidence, predictors, and mortality in ANCA-associated vasculitis (AAV).
We conducted a retrospective cohort study of all GPA or MPA, ...according to Chapel Hill Consensus Conference classification criteria, diagnosed between 1981 and 2015. Major cardiovascular event was defined as acute coronary artery disease, or ischemic stroke, or peripheral vascular disease requiring a revascularization procedure. We calculated the comparative morbidity/mortality figure (CMF) and we used Cox proportional hazards regression models to assess the risk of coronary artery disease, ischemic stroke associated with AAV, after adjusting for covariates.
125 patients, 99 GPA (79,2%) and 26 MPA (20,8%), were followed 88.4 ± 78.3 months. Ischemic stroke incidence was four times higher than in the general population (CMF 4,65; 95% CI 4,06-5,31). Coronary artery disease incidence was four times higher than in the general population (CMF 4,22; 95% CI 1,52-11,68). Smoking habits and history of coronary artery disease were strongly associated with coronary artery disease occurrence (adjusted HR 8.8; 95% CI 2.12–36.56, and adjusted HR 10.3; 95% CI 1.02–104.5, respectively). ENT flare-up was an independent protective factor for coronary artery disease occurrence. We did not identify factors significantly associated with stroke occurrence. The age-adjusted mortality rate was 22.5 per 1000 person-years. Mortality in AAV was 1.5 times higher than in the general population (CMF 1.56; 95% CI 1.34–1.83).
AAV have a significantly increased risk of mortality, ischemic stroke, and coronary artery disease.
•Patients with AAV have a four times more risk of ischemic stroke or coronary artery disease that in the general population.•Cardiovascular mortality in associated-ANCA vasculitis (AAV) patients is 1.5 times more than in the general population.•Monitoring for this complication and vigilance in modifying risk factors are warranted in this patient population.
L’intensification thérapeutique avec greffe de cellules souches hématopoïétiques autologues, développée depuis plus de 25 ans, a montré, dans trois essais cliniques randomisés et contrôlés, une ...amélioration significative non seulement de la survie sans événement, de la survie globale, de l’atteinte cutanée et pulmonaire mais aussi de la qualité de vie des patients porteurs d’une sclérodermie systémique cutanée diffuse récente sévère, par rapport à la prise en charge conventionnelle malgré une morbimortalité liée à la procédure mesurée entre 2,4 et 10 %. Aucun immunosuppresseur ou biomédicament utilisé dans la sclérodermie systémique n’a montré d’impact sur la mortalité de cette maladie. Le risque de rechute est estimé entre 9 et 24 %, 2 ans après la procédure. Fort de ces résultats, les recommandations françaises et internationales positionnent maintenant la greffe de cellules souches hématopoïétiques autologues selon un niveau de preuve 1A comme alternative thérapeutique dans les sclérodermies systémiques sévères précoces rapidement progressives.
Autologous haematopoietic stem cell transplantation for systemic scleroderma, developed over more than 25 years, has shown in three randomised controlled clinical trials a significant impact not only in event-free survival, overall survival, cutaneous and pulmonary involvement, but also in the quality of life of patients living with recent severe diffuse cutaneous systemic scleroderma, compared with IV cyclophosphamid despite a transplant-related mortality between 2.4 and 10%. No immunosuppressants or biologics have shown such an impact on mortality in this disease. The risk of relapse is estimated between 9 and 24%, two years after transplant. On the basis of these results, French and international guidelines now position autologous haematopoietic stem cell transplantation as a level 1A evidence-based therapeutic alternative in severe early and rapidly progressive systemic scleroderma.
•Interleukin 6 (IL-6) plays an important role in the pathogenesis of NMOSD.•Tocilizumab is a humanized monoclonal antibody that acts as an IL-6 receptor antagonist.•All our patients were relapse-free ...for the duration of tocilizumab treatment.•We confirm good tolerability and long-term efficacy of tocilizumab use in NMOSD and MOGAD.•Subcutaneous injections seem to have the same efficacy as intravenous injections and are simpler.
The objective of the study was to evaluate the indication, efficacy and safety of tocilizumab, a humanized anti–interleukin-6 receptor antibody, in patients with neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody associated diseases (MOGAD) encountered in current neurological practice.
We conducted a retrospective analysis of an exhaustive cohort of patients with inflammatory CNS disorders at Toulouse University Hospital, France, from 2014 to 2020. Efficacy was evaluated with clinical outcome by the Annual Relapse Rate, and radiological outcome with MRI data. The other outcomes were adverse events and effectiveness according to the form of injection (intravenous or subcutaneous).
Seven patients were treated with tocilizumab: four patients had NMOSD with AQP4+ antibodies (57%) and three had MOGAD (43%). Tocilizumab was administered in the presence of persistent clinical activity and/or severe side effects with other immunosuppressant medications.
The median follow-up on tocilizumab was 23 months (4–50 months). All patients started with monthly intravenous injection, then three switched to a subcutaneous form. All patients were relapse-free throughout the duration of treatment with tocilizumab, and one presented with a new cervical lesion on MRI. Four patients had no adverse effect, two had a significant increase in infection rate, and one had dyslipidemia.
tocilizumab appears to be an effective therapy for patients with refractory NMOSD or MOGAD. Subcutaneous and intravenous injections appear to be equally effective.
Management of giant cell arteritis (GCA, Horton's disease) involves many uncertainties. This work was undertaken to establish French recommendations for GCA management.
Recommendations were developed ...by a multidisciplinary panel of 33 physicians, members of the French Study Group for Large Vessel Vasculitis (Groupe d’étude français des artérites des gros vaisseaux GEFA). The topics to be addressed, selected from proposals by group members, were assigned to subgroups to summarize the available literature and draft recommendations. Following an iterative consensus-seeking process that yielded consensus recommendations, the degree of agreement among panel members was evaluated with a 5-point Likert scale. A recommendation was approved when ≥ 80% of the voters agreed or strongly agreed.
The 15 retained topics resulted in 31 consensus recommendations focusing on GCA nomenclature and classification, the role of temporal artery biopsy and medical imaging in the diagnosis, indications and search modalities for involvement of the aorta and its branches, the glucocorticoid regimen to prescribe, treatment of complicated GCA, indications for use of immunosuppressants or targeted biologic therapies, adjunctive treatment measures, and management of relapse and recurrence.
The recommendations, which will be updated regularly, are intended to guide and harmonize the standards of GCA management.
Hematopoietic stem cell transplantation (HSCT) for severe ADs was developed over the past 25years and is now validated by national and international medical societies for severe early systemic ...sclerosis (SSc) and relapsing-remitting multiple sclerosis (MS) and available as part of routine care in accredited center. HSCT is also recommended, with varying levels of evidence, as an alternative treatment for several ADs, when refractory to conventional therapy, including specific cases of connective tissue diseases or vasculitis, inflammatory neurological diseases, and more rarely severe refractory Crohn's disease. The aim of this document was to provide guidelines for the current indications, procedures and follow-up of HSCT in ADs. Patient safety considerations are central to guidance on patient selection and conditioning, always validated at the national MATHEC multidisciplinary team meeting (MDTM) based on recent (less than 3months) thorough patient evaluation. HSCT procedural aspects and follow-up are then carried out within appropriately experienced and Joint Accreditation Committee of International Society for Cellular Therapy and SFGM-TC accredited centres in close collaboration with the ADs specialist. These French recommendations were performed according to HAS/FAI2R standard operating procedures and coordinated by the Île-de-France MATHEC Reference Centre for Rare Systemic Autoimmune Diseases (CRMR MATHEC) within the Filière FAI2R and in association with the Filière MaRIH. The task force consisted of 3 patients and 64 clinical experts from various specialties and French centres. These data-derived and consensus-derived recommendations will help clinicians to propose HSCT for their severe ADs patients in an evidence-based way. These recommendations also give directions for future clinical research in this area. These recommendations will be updated according to newly emerging data. Of note, other cell therapies that have not yet been approved for clinical practice or are the subject of ongoing clinical research will not be addressed in this document.
La greffe de cellules souches hématopoïétiques (GCSH) pour les maladies auto-immunes (MAI) sévères s’est développée au cours des 25 dernières années et est maintenant validée par les sociétés savantes nationales et internationales pour la sclérodermie systémique sévère précoce et la sclérose en plaques récurrente-rémittente et est disponible dans le cadre des soins courants dans des centres accrédités. La GCSH est également recommandée, avec des niveaux de preuve variables, comme traitement alternatif pour plusieurs MAI, lorsqu’elles sont réfractaires aux thérapies conventionnelles, comprenant des cas spécifiques de connectivites ou de vascularites ; des maladies neuro-inflammatoires ; et plus rarement les maladies de Crohn réfractaires sévères. L’objectif de ce document est de fournir des recommandations sur les indications actuelles, les procédures et le suivi de la GCSH dans les MAI. La sécurité des patients reste l’élément majeur guidant la sélection et le conditionnement des patients, toujours validées lors de la réunion de concertation pluridisciplinaire nationale MATHEC sur la base d’une évaluation exhaustive et récente (moins de 3 mois) du patient. La GCSH et le suivi sont ensuite effectués dans des centres expérimentés et accrédités par le Joint Accreditation Committee of International Society for Cellular Therapy et la SFGM-TC, en étroite collaboration avec le spécialiste des MAI. Ces recommandations françaises ont été réalisées conformément aux procédures opérationnelles standard de la HAS/FAI2R et coordonnées par le Centre de référence des maladies auto-immunes systémiques rares d’Île-de-France MATHEC (CRMR MATHEC) au sein de la Filière FAI2R et en association avec la Filière MaRIH. Le groupe de travail était composé de 3 patients et de 64 cliniciens experts issus de différentes spécialités et de différents centres français. Ces recommandations issues des données publiées et de consensus d’experts aideront les cliniciens à proposer la GCSH à leurs patients atteints de MAI sévère. Ces recommandations ouvrent également des perspectives de recherche clinique. Ces recommandations seront régulièrement mises à jour en fonction des nouvelles données publiées. Il convient de noter que les autres thérapies cellulaires qui n’ont pas encore été approuvées par les autorités de santé ou qui font l’objet d’essais cliniques en cours ne seront pas abordées dans ce document.
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