Background: Standard therapy is ill-defined for patients with systemic lupus erythematosus (SLE) suffering from the membraneous form of Lupus nephritis (WHO class V). Therapeutic options used at present include azathioprine. In a small, open label safety study, patients with lupus nephritis, including patients with membraneous lupus nephritis, have experienced a long-lasting therapeutic response, with sustained reduction in proteinuria, following a 10 weeks course of 4 infusions of infliximab in combination with azathioprine. This short course appeared safe with regard to SLE activity, despite increases in autoantibody levels. Study hypothesis: 1. The combination of four infusions of infliximab (5 mg/kg of body weight)administered at weeks 0, 2,6, and 10, with azathioprine will be faster than azathioprine alone in reducing proteinuria to less than 1.5 g/day in patients with active lupus nephritis WHO class V (proteinuria \> 3g/day). 2. This combination therapy will show a tolerable safety profile with regard to SLE activity and infections.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
1
azathioprine (2 mg/lkg) plus four infusions of infliximab (5mg/kg)
azathioprine (2 mg/kg) plus four placebo infusions
Departments of Rheumatology, Internal Medicine, Medical University of Graz
Graz, Austria
Rheumatology, Internal Medicine III, Medical University of Vienna
Vienna, Austria
Internal Medicine II, Hietzing Hospital
Vienna, Austria
Rheumatology, Charite
Berlin, Germany
Rheumatology, University of Düsseldorf
Düsseldorf, Germany
Internal Medicine III, University of Erlangen
Erlangen, Germany
Clinical Immunology, Groningen University Hospital
Groningen, Netherlands
Leiden University Medical Center, Netherlands
Leiden, Netherlands
Nephrology, University of Nymegen, Netherlands
Nijmegen, Netherlands
Comparison of time needed to reduce proteinuria to 1.5 g/day or less between the infliximab plus azathioprine and the azathioprine only group.
Percentage of patients reaching reduction in proteinuria to ≤ 1.5 g/day, at week 12 and week 52.
Percent reduction in proteinuria at 6 weeks, 12 weeks, 20 weeks, 36 weeks, and 52 weeks after the first infusion.
Absolute reduction in proteinuria at 6 weeks, 12 weeks, 20 weeks, 36 weeks, and 52 weeks after the first infusion.
Percent reduction in protein/ creatinine ratio.
Percent reduction in SLE disease activity (measured by SIS and SLEDAI).
Absolute reduction in SLE disease activity (measured by SIS and SLEDAI).
Changes in Quality of life as determined by the SF36 questionnaire.
Changes in Fatigue as determined by the FSS (Fatigue Severity Scale).
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