Overview

Rituximab for the Treatment of Refractory Inflammatory Myopathies and Refractory Myasthenia Gravis

Status:
Completed

Trial end date:
2011-12-01

Target enrollment:
0

Participant gender:
All

Summary

The traditional treatment of inflammatory myopathies (IM) and generalized myasthenia gravis (MG) is immunosuppressive therapy, usually beginning with corticosteroids. However, up to 70% of treated patients show an incomplete response, including 10 - 30% who are unresponsive. Corticosteroids and other immunosuppressive therapies presented also many side effects. We propose to evaluate in a pilot, open, prospective, multicentric, phase II study, the interest of rituximab in the treatment of patients with primary IM associated with specific AAb (anti-synthetase and anti-SRP AAbs), or MG (with anti-AchR AAbs), refractory to conventional therapies. Twenty fourth patients with primary IM (12 with anti-synthetase, 12 with anti-SRP AAbs), and 12 with MG will be included in the study.

Phase:

Phase 2

Accepts Healthy Volunteers?

Details

Lead Sponsor:

Assistance Publique - Hôpitaux de Paris

Collaborators:

Institut National de la Santé Et de la Recherche Médicale, France
Roche Pharma AG

Treatments:

Rituximab

Criteria

Inclusion Criteria:

- For myositis III. Idiopathic myositis

1. Myositis as defined by the 119th ENMC:

1. Proximal myopathy with weakness

2. Subacute or insidious onset over 18 years

3. Myogenic syndrome on EMG (optional)

4. Muscle fibre necrosis and regeneration and/or inflammatory cell infiltrate
on muscular biopsy

2. Specific AAbs : anti-synthetases (anti-JO1, anti-PL7, or anti-PL12), or anti-SRP.

IV. Refractory to the conventional treatments Resistance to conventional
treatments is defined as an inadequate response to, or intolerable side effects
with conventional treatments, such as corticosteroids, azathioprine,
methotrexate, cyclophosphamide, cyclosporine, IgIV and/or plasma exchange. At
least one or more of these drugs or therapeutical approaches (used alone or as a
combination) must have been unsuccessfully tested before inclusion. Inadequate
response is defined as the lack of improvement and/or the degradation of
evaluation parameters (defined bellow) despite these conventional therapies, that
led to a modification or a reintroduction of treatment.

- For myasthenia III. Generalised MG

Generalised seropositive MG as defined by the Texas Clinical Classification System:

1. Extraocular muscle weakness quantified with MG muscle score (MMS), whose inter and
inter observer reproducibility has been demonstrated [44].

2. Specific AAbs : anti-AchR IV. Refractory to the conventional treatments Resistance to
conventional treatments is defined as an inadequate response to, or intolerable side
effects with conventional treatments, such as corticosteroids, azathioprine,
methotrexate, cyclophosphamide, cyclosporine, IgIV and/or plasma exchange. At least
one or more of these drugs or therapeutical approaches (used alone or as a
combination) must have been unsuccessfully tested before inclusion. Inadequate
response is defined as the lack of improvement and/or the degradation of evaluation
parameters (defined bellow) despite these conventional therapies, that led to a
modification or a reintroduction of treatment

Exclusion Criteria:

- Other muscular diseases, such as:

1. Inclusion body myositis

2. Macrophagic myofasciitis

3. Inherited myopathies

- Secondary IM to one other connective tissue disorders

1. Systemic scleroderma (ARA and/or "LEROY AND MEDSGER" criteria)

2. Sjögren's syndrome (European criteria)

3. Systemic lupus erythematosus (ACR criteria)

4. Rheumatoid arthritis (ACR criteria)

5. Mixed connective tissue disease (ACR criteria)

- Other myasthenic syndrome, such as:

1. Non generalised, ocular MG

2. Lambert Eaton syndrome

3. MG associated with malignant thymoma

4. Inherited myasthenic syndrome

- Cancer (or cancer-associated myositis)

- Age < 18 years

- Pregnancy

- HIV seropositivity

- Evolutive infection (B, C hepatitis, tuberculosis)

- Lack of approved consent