RITUXIMAB, efficace et durable pour les MG AC RAch positives.

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RITUXIMAB, efficace et durable pour les MG AC RAch positives.

Message par Pboulanger » 13 déc. 2016 05:01


Lu sur http://www.medscape.com/viewarticle/872972
Traduction disponible directement en cliquant en bas à droite de ce message sur notre forum

Rituximab Effective, Durable in Refractory Acetylcholine Receptor Autoantibody-Positive Myasthenia Gravis

Laurie L. Barclay, MD
Disclosures | December 12, 2016

Durability of the Rituximab Response in Acetylcholine Receptor Autoantibody-Positive Myasthenia Gravis

Robeson KR, Kumar A, Keung B, et al
JAMA Neurol. 2016 Nov 21.


Many current treatments for myasthenia gravis (MG) are nonspecific immunotherapeutics, to which a subset of patients is medically refractory. Previous studies have suggested that B-cell–targeted treatment with rituximab has efficacy in MG, but the duration of treatment response was undetermined.

The goal of this retrospective case series was to assess the durability of response to rituximab in 16 patients (10 women; median age, 42 years) with acetylcholine receptor autoantibody-positive (AChR+) generalized MG. All patients were referred to an MG clinic between January 1, 2007, and December 31, 2015, and they had clinical improvement on rituximab even during complete discontinuation or reduction of other immunotherapies.

At 18- to 84-month follow-up after rituximab treatment, all patients had complete stable remission, pharmacologic remission, or minimal manifestations based on Myasthenia Gravis Foundation of America criteria. Nine patients (56%) relapsed at a mean follow-up of 36 months, whereas seven (44%) did not relapse during a follow-up of 47 months since last rituximab treatment. Those who relapsed improved clinically after further immunosuppressive treatment.

After cycle 1 of rituximab treatment, there was a 33% decrease from pretreatment anti-AChR antibody level (normalized to 100% pretreatment vs 67% after cycle 1; P = .004). There were additional decreases with subsequent treatment cycles (20% after cycle 2, P = .008; and 17% after cycle 3, P = .02), but there were no changes in serum cytokine levels. Rituximab was well tolerated, without severe hematologic disturbances or infusion reactions.

The rationales for using rituximab in the treatment of MG include its mechanism of action targeting B cells, which are implicated in MG, and its use as a successful treatment in rheumatoid arthritis and other autoimmune diseases.

This study is limited by its retrospective design, small sample size, and possible confounding by thymectomy status. Nonetheless, the findings suggest that rituximab appears to be an effective treatment option for patients with refractory AChR+ MG, achieving a durable response. Most patients needed approximately 1 year before being able to taper other treatments, suggesting that at least two rituximab cycles are needed. Patients without medical contraindications, with clinical disease relapse, and with at least 6 months elapsing since the last cycle should be considered for retreatment.

Despite the rarity of progressive multifocal leukoencephalopathy, given its extremely poor prognosis, clinical monitoring per best medical practice standards is indicated when considering rituximab treatment, as well as minimizing combination immunosuppressive regimens. For rituximab to be incorporated into evidence-based practice for MG treatment, pathophysiologically relevant biomarkers of disease relapse and sustained remission are needed. An ongoing prospective, placebo-controlled clinical trial is currently assessing rituximab efficacy, safety, and pharmacodynamics in MG.



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