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Myasthenia Gravis

Muscle Weakness

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Asthenia

Muscular Diseases

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Paraneoplastic Syndromes, Nervous System

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Autoimmune Diseases of the Nervous System

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Neuromuscular Diseases

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Prednisone

Rituximab

Antineoplastic Agents, Immunological

Immunologic Factors

Immediate standardized treatment with corticosteroids. Standardized treatment in the experimental arm will start at 0.5mg/kg/d prednisone.

immediate treatment with corticosteroids

rituximab added if ocular symptoms reappear as corticosteroids are tapered off. Rituximab will be given at a dose of 500mg/6months for 12 months.

addition of rituximab if recurrence

Myasthenia is an autoimmune disease causing dysfunction of the neuromuscular junction, resulting in fluctuating and variable muscle weakness.

In the initial phase of the disease, 70% of patients present with ocular onset myasthenia (OMG), i.e. weakness limited to the oculomotor muscles. Generalization to skeletal, bulbar and axial muscles occurs in 20-40% of cases, with a higher frequency in the first and second years, respectively 46% and 60% of generalizations. This reflects the maturation of the autoimmune response in the early years of the disease, and represents a therapeutic window of opportunity to modify the course of the disease.

Generalization is a critical event, putting the patient at risk of admission to an intensive care unit and necessitating the use of long-term immunosuppressants.

There is currently no validated strategy for preventing generalization. On the one hand, a preventive role for corticosteroid therapy in ocular-onset myasthenia has been observed in some studies, but not confirmed by others. These contradictory results may be explained by the bias of retrospective observational studies and the use of different corticosteroid administration regimens.

On the other hand, recent data on the use of low-dose Rituximab in the early phase of the disease shows greater efficacy than later use, enabling prolonged remission of the disease with a very good tolerability profile.

We propose to compare in a randomized controlled trial the usual practice with a proactive strategy with a standardized corticosteroid regimen immediate at diagnosis.

Patients with ocular myasthenia are usually treated symptomatically with acetylcholinesterase inhibitors. The introduction of corticosteroids is delayed and limited to patients with persistent disabling diplopia or ptosis with occlusion. When corticosteroids are tapered off, ocular symptoms may recur. This level of corticosteroid dependence observed in patients treated for ocular myasthenia has not been specifically studied. In order to reduce the levels of corticosteroids administered and avoid recurrence of ocular symptoms and their delayed generalization, it is usually proposed to introduce another immunosuppressant.

The aim of this study is to evaluate the efficacy of a standardized proactive prevention strategy on the generalization of ocular onset myasthenias during the first 2 years. It will combine immediate treatment with corticosteroids at the time of diagnosis, with the addition of rituximab in the event of recurrence of ocular symptoms as corticosteroids are tapered off.

Immediate Corticosteroid Therapy and Rituximab to Prevent Generalization in Ocular Myasthenia: a PROBE Multicenter Open-label Randomized Controlled Trial.

Generalization is defined by a loss of 5 points or more on any Myasthenic Muscle Score (MMS) item, excluding "eyelid occlusion" and "extrinsic ocular musculature".

Progress towards generalization will be assessed by an expert physician, blinded to the intervention arm.

Fondation Ophtalmologique Adolphe de Rothschild

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Immediate Corticosteroid Therapy and Rituximab to Prevent Generalization in Ocular Myasthenia: a PROBE Multicenter Open-label Randomized Controlled Trial.	NCT06342544	Ocular Myasthen...	immediate treat... addition of rit...	18 Years -	Fondation Ophtalmologique Adolphe de Rothschild
Immediate Corticosteroid Therapy and Rituximab to Prevent Generalization in Ocular Myasthenia: a PROBE Multicenter Open-label Randomized Controlled Trial.	NCT06342544	Ocular Myasthen...	immediate treat... addition of rit...	18 Years -	Fondation Ophtalmologique Adolphe de Rothschild

Spots Global Cancer Trial Database for addition of rituximab if recurrence