Systemic sclerosis
Conditions
Interventions
Group A:Rituximab 500mg + original standard therapy (52 weeks)
Group B:Rituximab 1000mg + original standard therapy (52 weeks)
Group C:Placebo + original standard therapy. Patients with poor efficacy at 24 weeks as assessed by a non-blinded team were randomized to treatment in the rituximab 500 mg group or the 1000 mg group.
Sponsors
Department of Rheumatology and immunology, Huashan Hospital, Fudan University
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: To be eligible for the study, patients had to meet all of the following eligibility criteria: 1.Patients with SSc meet the 2013 American College of Rheumatology/European Union League Against Rheumatism classification criteria 2. Poor response to previous therapy (poor response or intolerance to continuous use for at least three months) and ongoing disease progression as assessed by the investigator, including but not limited to skin progression or worsening of gastrointestinal involvement or progressive pulmonary fibrosis or Raynaud's disease or uncontrolled pulmonary hypertension. 3. Oral corticosteroids (=10 mg/ day of prednisone or equivalent) are allowed, provided a stable dose regimen was administered for 2 or more weeks before(or at) the baseline visit 4. If methotrexate =7.5mg weekly or mycophenolate mofetil =1.0g daily is used as oral background therapy, a stable dose should be used for at least 12 weeks 5. PDE-5 inhibitors and/or endothelin antagonists are permitted as oral treatments for Raynaud, fingertip ulcers, or pulmonary hypertension 6. Age =18 years old and =70 years old 7. Be able to provide informed consent. The institutional review board (IRB)/ Ethics review board (ERB) -approved informed consent form at the study site must be read and understood, and written informed consent must be provided
Exclusion criteria
Exclusion criteria: Subjects with any of the following characteristics/conditions will not be included in the study: 1. SSc is currently in a stable state 2. SSc have got major trauma or surgery (including joint surgery) within 8 weeks before baseline, or require major surgery during the study, whiich are deemed by the investigator to pose an unacceptable risk to patients 3. Any active infectious diseases at screening that was judged by the investigator to be ineligible for study entry 4. The subject has had any serious bacterial infection in the past 2 weeks (except those who recovered after antibiotic treatment), or any chronic bacterial infection (e.g., chronic pyelonephritis, osteomyelitis, or bronchiectasis). 5. Oral corticosteroids > 10 mg/ day prednisone or equivalent. 6. Received anti-CD20 therapy 6 months before baseline or previously had poor response to CD20 monoclonal antibodies. 7. Hydroxychloroquine > 400 mg/ day, methotrexate > 25 mg/ week, and mycophenolate mofetil > 2 g/ day ** Subjects could receive a combination of hydroxychloroquine and methotrexate or a combination of hydroxychloroquine and mycophenolate mofetil and had to be on a stable dose for at least 1 month before the baseline visit 8. a. Received biologic treatment for an immune disorder within 4 weeks prior to screening, such as etanercept, infliximab, cetuzumab, adalimumab, golimumab, tocilizumab, abatacept, ustkinumab, ezetimizumab, secukinumab, or anakinrachtin b. Receipt of belimumab or anifrolumab (or other anti-IFN therapy) within 12 weeks before screening c. Any other B cell-depleting therapy or intravenous immunoglobulin (IVIg) within 24 weeks before screening d. received JAK inhibitor therapy =4 weeks (or 5 drug half-life times, whichever was longer) before baseline e. Receipt of other immunosuppressive therapy within 4 weeks before baseline 9. Receipt of any study drug for =4 weeks before baseline (or five half-lives of the study drug, whichever was longer) 10. Receipt of other investigational or marketed biologic agents with immunomodulatory properties within 3 months before baseline 11. Lung disease with FVC=50% of predicted value or DLCO (unadjusted hemoglobin) =40% of predicted value 12. Subjects at risk for tuberculosis (TB) A. Specifically excluded from the study was a history of active TB within the previous 3 years, even if treated; A history of active TB of more than 3 years unless appropriate duration and type of previous anti-TB treatment was documented; Current clinical, imaging, or laboratory evidence of active TB; TB results obtained within 30 days before screening will be accepted and not repeated. b. Patients with latent TB at screening or within 30 days before screening, history of QuantiFERON Gold testing, negative chest radiography, and no symptoms or risk factors were eligible to receive concomitant TB prophylaxis c.QuantiFERON® indeterminate, twice indeterminate as latent TB prophylaxis 13. Hepatitis B HBV-DNA test was positive Patients with hepatitis B virus (HBV) infection, currently receiving anti-HBV treatment, and negative for HBV-DNA were eligible, and HBV-DNA was monitored during the study 14. Tested positive for hepatitis C Have hepatitis C virus (HCV) infection (positive for hepatitis C antibodies and positive for HCV RNA [RNA]) Note: Patients with documented previous anti-HCV treatment for HCV infection and negative RNA for HCV were eligible for inclusion. 15. Current or recent history of uncontrolled clinically significant renal, hepati
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Modified Rodnan skin score, mRSS;General impression of the patient's general health;SHAQ-DI;Pulmonary function; | — |
Secondary
| Measure | Time frame |
|---|---|
| 28 joint pain assessment forms;28 joint swelling assessment sheet;SGRQ;Gastrointestinal assessment questionnaire;SSPRO;ScleroID;HRCT of the lungs; | — |
Countries
China
Contacts
Public ContactYu Xue
Department of Rheumatology, Huashan Hospital, Fudan University
Outcome results
None listed