Rituximab in Systemic Sclerosis

Assistance Publique - Hôpitaux de Paris22 enrolled

Overview

The purpose of this study is to determine whether rituximab is effective in the treatment of articular symptoms that occur in systemic sclerosis related polyarthritis

Systemic sclerosis (SSc) is a rare disease, characterized by microvascular and immunological changes promoting extra-cellular matrix synthesis and widespread fibrosis. No treatment has yet proven any ability to alter the disease fibrosing process. Specific auto-antibodies are commonly found in this disease, and B lymphocytes are detected in cutaneous and pulmonary infiltrates. Studies derived from murine models suggest a role for B lymphocyte blocking strategies. This lead to observational trials of B-cell therapy using rituximab in SSc that provided encouraging results with no particular signal concerning tolerability. These trials included heterogeneous patients with variable disease stages and different involved organs, and were mostly unblinded, which preclude any definitive conclusion. However, they support the continuous development of this therapeutic approach. Taking up the early phase of the diffuse form of the disease is complicated by its rarity and the heterogeneous progression of its visceral complications. This raises the question of selecting a homogeneous group of patients to evaluate. The most convincing results for the use of rituximab in autoimmune conditions have been found in rheumatoid arthritis. Joint involvement is common in SSc with 75% of patients complaining about joint stiffness and pain, and 30% presenting with synovitis, tenosynovitis, or flexion contractures. No specific treatment has already addressed this issue, and it is generally proposed to use small doses of oral corticosteroids in association with methotrexate, by analogy with rheumatoid arthritis. We propose to evaluate the efficacy and safety of rituximab in SSc patients having active arthritis despite first line treatment. Improving the articular involvement would improve the quality of life f SSc patients and effectiveness of rituximab on skin and lung fibrotic involvements will be assessed as secondary outcomes to estimate the overall effects of this drug on SSc.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Systemic Sclerosis

Interventions

RituximabDRUG

Days 1 and 15, rituximab 1 gramme plus 100 mg methylprednisolone

Placebo (NaCl)DRUG

Days 1 and 15, NaCl 500 ml plus 100 mg methylprednisolone

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Systemic sclerosis fulfilling ACR or LeRoy's criteria * Active polyarthritis defined by \> 6/53 tender joints and \> 4/53 swollen joints * Ongoing first line therapy by prednisone (max 10 mg/d) and DMARDS (methotrexate, leflunomide, azathioprine or mycophenolate) * Birth control if applicable Exclusion Criteria: * Overlap syndrome defined by clinical symptoms and positive specific auto-antibodies (anti-CCP, anti-SSA, anti-DNA DNA anti-Sm) (Rheumatoid factors and anti-RNP are not exclusion criteria) * Past therapy with Rituximab. * Severe and uncontrolled disease with renal, liver or haematological (neutropenia \< 1500 / mm3) failures, pulmonary (FVC \< 50%) or cardiac insufficiencies (LVEF \< 50%) * Not stable corticosteroid therapy or cyclophosphamide use in the last 6 months * Infectious risk : viral infections by B or C hepatitis or HIV, hypogammaglobulinemia (\< 6 G/L), opportunistic infection or infection requiring IV antibiotics in the last 3 months. * Neoplastic solid tumor in the last 5 years * Drug or alcool abuses * Receiving patient or having received a biotherapy (anti-TNF, abatacept or tocilizumab) in the last 3 months (possible inclusion beyond 3 months)

Locations (1)

Cochin Hospital

Paris, France

Outcomes

Primary Outcomes

Number of tender and swollen joints

Measured out of 53 joints

Time frame: at 6 months