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

Sponsor
Fondation Ophtalmologique Adolphe de Rothschild
Study ID
NCT06342544
Phase
PHASE3
Status
Recruiting
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Conditions

  • Ocular Myasthenia Gravis

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • immediate treatment with corticosteroids — DRUG
    Immediate standardized treatment with corticosteroids. Standardized treatment in the experimental arm will start at 0.5mg/kg/d prednisone.
  • addition of rituximab if recurrence — DRUG
    rituximab added if ocular symptoms reappear as corticosteroids are tapered off. Rituximab will be given at a dose of 500mg/6months for 12 months.

Study Details

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.

Key Dates

Start date
Apr 29, 2025
Status verified
Jan 2026
Primary completion
Jun 30, 2028
Completion
Jun 30, 2029

Study Design

Enrollment
128 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: immediate treatment with corticosteroids addition of rituximab if recurrence
  • No Intervention: based on standard practice

Primary Outcome Measure

proportion of patients who progressed to generalized myasthenia within 2 years of follow-up [ Time Frame: Day0 to month24 ]

Central Contacts

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