Systemic Sclerosis
Conditions
Keywords
Systemic sclerosis, Arthritis, B-cell therapy, Anti-CD20 therapy, Quality of life, Scleroderma, Lung fibrosis, Randomised controled trial
Brief summary
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
Detailed description
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.
Interventions
DRUGRituximab
Days 1 and 15, rituximab 1 gramme plus 100 mg methylprednisolone
DRUGPlacebo (NaCl)
Days 1 and 15, NaCl 500 ml plus 100 mg methylprednisolone
Sponsors
URC-CIC Paris Descartes Necker Cochin
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of tender and swollen joints | at 6 months | Measured out of 53 joints |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quality of life: SSc-HAQ | at 6 and 12 months | Validated scores |
| Scleroderma | at 6 and 12 months | modified Rodnan skin score |
| Lung fibrosis | at 6 and 12 months | Pulmonary functional tests |
| Quality of life: SF-36 | at 6 and 12 months | Validated scores |
| Quality of life: Duruöz index | at 6 and 12 months | Validated scores |
Countries
France
Outcome results
None listed