Le Rituximab (RTX) est un anticorps monoclonal antiCD20 qui a montré son efficacité et sa bonne tolérance dans la myasthénie généralisée (MG). Le schéma d’administration est variable selon les ...équipes.
Évaluer l’intérêt du dosage sanguin des LB-CD27+ comme marqueur biologique de rechute de la MG dans le but d’adapter la fréquence d’administration du RTX.
Depuis 2015, 32 patients myasthéniques ont été traités par RTX. Les patients reçoivent une cure d’induction (1g J1 et J15). Une évaluation clinique (score myasthénique) et des paramètres biologiques (LB-CD19+, LB-CD27+, Rituximabémie et Ac anti-RTX) sont réalisés tous les 3 mois. En cas de réémergence des LB-CD 27+ (le seuil de détection est à 0,05 % PBMC), une cure d’entretient de RTX (1g) est réalisée.
Trente-deux patients ont été évalués : âge moyen de 52 ans (18–92 ans ; 53 % de femmes), 90 % Ac anti-Rach+, 3 % Ac anti-Musk+ et 12 % Ac anti-Titine. À l’induction, le score myasthénique moyen est de 70/100 (22/100–100/100). Quarante-quatre pour cent des patients avaient reçu un ou plusieurs traitements immunosuppresseurs et 56 % étaient naïfs de traitement de fond. Le délai moyen de réemergence des LB-CD27+ est de 7 mois (2–12) avec un score myasthénique moyen de 81/100 (56/100–100/100).
Le suivi des LB-CD27+ a permis d’identifier des patients avec réémergence précoce (2 mois) et d’autres nécessitant un espacement des cures jusqu’à un an, évitant ainsi des perfusions inutiles, des économies et une diminution de la toxicité. Il n’y a eu aucune rechute clinique sévère lors des espacements de cures ni aucun effet secondaire grave.
Le suivi des LB-CD27+ permet une réduction du nombre de cures avec une bonne efficacité clinique. Ce marqueur sera d’autant plus intéressant économiquement avec l’émergence des nouveaux anti-CD20.
Background: The effects of socio-economic status on mortality in patients with multiple sclerosis is not well known. The objective was to examine mortality due to multiple sclerosis according to ...socio-economic status. Methods: A retrospective observational cohort design was used with recruitment from 18 French multiple sclerosis expert centers participating in the Observatoire Français de la Sclérose en Plaques. All patients lived in metropolitan France and had a definite or probable diagnosis of multiple sclerosis according to either Poser or McDonald criteria with an onset of disease between 1960 and 2015. Initial phenotype was either relapsing-onset or primary progressive onset. Vital status was updated on January 1st 2016. Socio-economic status was measured by an ecological index, the European Deprivation Index and was attributed to each patient according to their home address. Excess death rates were studied according to socio-economic status using additive excess hazard models with multidimensional penalised splines. The initial hypothesis was a potential socio-economic gradient in excess mortality. Findings: A total of 34,169 multiple sclerosis patients were included (88% relapsing onset (n = 30,083), 12% progressive onset (n = 4086)), female/male sex ratio 2.7 for relapsing-onset and 1.3 for progressive-onset). Mean age at disease onset was 31.6 (SD = 9.8) for relapsing-onset and 42.7 (SD = 10.8) for progressive-onset. At the end of follow-up, 1849 patients had died (4.4% for relapsing-onset (n = 1311) and 13.2% for progressive-onset (n = 538)). A socio-economic gradient was found for relapsing-onset patients; more deprived patients had a greater excess death rate. At thirty years of disease duration and a year of onset of symptoms of 1980, survival probability difference (or deprivation gap) between less deprived relapsing-onset patients (EDI = −6) and more deprived relapsing-onset patients (EDI = 12) was 16.6% (95% confidence interval (CI) 10.3%–22.9%) for men and 12.3% (95%CI 7.6%–17.0%) for women. No clear socio-economic mortality gradient was found in progressive-onset patients. Interpretation: Socio-economic status was associated with mortality due to multiple sclerosis in relapsing-onset patients. Improvements in overall care of more socio-economically deprived patients with multiple sclerosis could help reduce these socio-economic inequalities in multiple sclerosis-related mortality. Funding: This study was funded by the ARSEP foundation “Fondation pour l'aide à la recherche sur la Sclérose en Plaques” (Grant Reference Number 1122). Data collection has been supported by a grant provided by the French State and handled by the “Agence Nationale de la Recherche,” within the framework of the “Investments for the Future” programme, under the reference ANR-10-COHO-002, Observatoire Français de la Sclérose en Plaques (OFSEP).
Prior to the era of disease-modifying therapies (DMT), multiple sclerosis (MS) was linked to reduced rates of cancer. Early use of immunosuppressors (IS) in MS justifies the follow-up of patients to ...evaluate a possible increase in the incidence of cancer in these patients. We performed a descriptive study of MS patients with a documented oncological event. Among the 22,563 MS patients in the EDMUS databases, patients with a history of cancer were identified, and cancer risk in a multiple sclerosis cohort (CARIMS) was evaluated. Four groups were defined: (A) MS patients without cancer receiving DMT or not, (B) MS patients with cancer but without any history of DMT, (C) MS patients with cancer who received an immunomodulator (IM), and/or (D) MS patients treated with an IS. A total of 9,269 patients (44.1%) had a history of DMT (52% IM; 18% IS; 30% both); 253 patients with MS and cancer were identified, 182 had a history of DMT. The mean duration of DMT was longer for group D (A: 3.6 years vs. D: 4.9 years;
P
< 0.01). There was no increased risk of cancer among patients treated exclusively with IM. IS treatment (
P
= 0.043) and the duration of exposure (
P
< 0.001) significantly increased the risk of cancer, especially skin cancer, as observed in other autoimmune diseases. This result could influence the attitude of the medical profession with respect to the benefit to risk ratio when proposing DMT to MS patients.
At the present time, there are no proven beneficial effects of chemotherapy (CT) for the treatment of pure low‐grade astrocytomas. Brain radiotherapy (RT) still remains the standard treatment in ...order to reduce or delay tumor progression or symptoms, despite possible long‐term neurologic complications. We report 10 patients, with histologically proven pure low‐grade fibrillary astrocytomas, to which we administered a first‐line nitrosourea‐based CT. All patients were symptomatic with pharmaco‐resistant epilepsy or neurologic symptoms, and had been rejected for neurosurgical resection. All patients with epilepsy had a clinical improvement with reduction in seizure frequency and 60% became seizure‐free. CT was well tolerated; all patients developed myelosuppression with 40% of grade III/IV hematotoxicity. Seven were alive at the time of writing with a mean follow‐up of 6.5 years (3.5–12) from first recorded symptoms. The three deceased patients died 7.5, 7.5, and 8.5 years from first symptoms. These results demonstrate that some patients with symptomatic non‐resectable fibrillary low‐grade astrocytomas can be treated with up‐front CT to improve their neurologic status. This report suggests that benefits of CT on symptoms, survival, and quality of life should be prospectively compared with RT.
Background: Time matters in multiple sclerosis (MS). Irreversible neural damage and cell loss occur from disease onset. The MS community has endorsed a management strategy of prompt diagnosis, timely ...intervention and regular proactive monitoring of treatment effectiveness and disease activity to improve outcomes in people with MS.
Objectives: We sought to develop internationally applicable quality standards for timely, brain health–focused MS care.
Methods: A panel of MS specialist neurologists participated in an iterative, online, modified Delphi process to define ‘core’, ‘achievable’ and ‘aspirational’ time frames reflecting minimum, good and high care standards, respectively. A multidisciplinary Reviewing Group (MS nurses, people with MS, allied healthcare professionals) provided insights ensuring recommendations reflected perspectives from multiple stakeholders.
Results: Twenty-one MS neurologists from 19 countries reached consensus on most core (25/27), achievable (25/27) and aspirational (22/27) time frames at the end of five rounds. Agreed standards cover six aspects of the care pathway: symptom onset, referral and diagnosis, treatment decisions, lifestyle, disease monitoring and managing new symptoms.
Conclusion: These quality standards for core, achievable and aspirational care provide MS teams with a three-level framework for service evaluation, benchmarking and improvement. They have the potential to produce a profound change in the care of people with MS.
This review summarizes papers published during 1991 and 1992. The poor results obtained in the postneurosurgical treatment of gliomas led researchers to pursue attempts to try to overcome glioma cell ...resistance. The intra-arterial route was explored in several phase II studies with new drugs and even immunoconjugates; rates of response between 30% to 60% were obtained. New drugs (fotemustine, eflornithine, and estramustine) or combined protocols planned to circumvent chemoresistance were tested and showed some efficiency with moderate toxicity, enlarging the number of drugs available against malignant gliomas. On the contrary, two retrospective analyses warned about the risk of reduction of median time to survival due to adjuvant chemotherapy in anaplastic astrocytomas; this finding, if confirmed, would suggest to defer chemotherapy at the time of recurrence in this type of glial tumor. Immunobiologic therapies as immunomodifiers, immunoconjugates, or cytotoxic lymphocyte-activated killer cells and tumor-infiltrating lymphocytes were tested and allowed some responses to be obtained. In young children, chemotherapy regimens were found to be efficient in malignant plexus choroid carcinomas and low-grade gliomas, allowing radiation therapy to be deferred. Many studies were methodologically unsatisfactory because of uncertain pathology grouping, noncompliance to initial protocols, or too small populations of patients.
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