Induction Therapy for Lupus Nephritis With no Added Oral Steroids: A Trial Comparing Oral Corticosteroids Plus Mycophenolate Mofetil (MMF) Versus Obinutuzumab and MMF

Preliminary data show that the anti CD20 monoclonal antibody may effectively replace oral corticosteroids in the induction treatment of lupus glomerulonephritis. The concept of avoiding significant use of corticosteroids would mark a step change in the approach to the treatment of lupus nephritis but the efficacy of such a strategy first needs to be confirmed in a randomised controlled study. The main aim of this study is to demonstrate that patients with lupus nephritis could be treated successfully without using damaging doses of oral corticosteroids. Eligible patients will be randomised with 1:1 ratio, between interventional group (obinutuzumab, IV methylprednisolone, no or low dose corticosteroids and MMF) and control group (oral prednisone, IV methylprednisolone and MMF), after signed informed consent obtaining. Randomization will be blocked and stratified by level of proteinuria (\<1 g/g versus ≥ 1 g/g). Previous 52 centers will participate to the trial. Study assessments will occur on a standard of care basis at 15 days, 1, 3, 6, 9 and 12 months (and at any flare or according to the wishes of the investigator). Study assessment will include assessment of disease activity, disease- and treatment-related damage, quality of life, and blood and urine tests as standard of care. In addition, a biobank will be sampled at inclusion. Long-term data on damage and renal function will be collected during standard of care (18 months, 2, 5 and 10 years) in patients who consented. Population involved: Children (14 years and above) and adults with lupus nephritis ISN/RPS class III or IV (A or A/C) ± V with active lesions in at least 10% of the viable glomeruli, AND urine protein-to-creatinine ratio (uPCR) ≥ 0.5 g/g. Data Analysis In summary, the primary outcome is complete renal response (CR), initial analysis will be descriptive, using odds ratios and 95% confidence intervals (CIs). Formally CR will be analysed using Intention-To-Treat (ITT) analysis via logistic regression. Following the ITT principle, missing data will be imputed. The model will include the treatment effect, and the factors used for stratification in the randomisation as covariates. Odd ratios and 95% CIs derived from the logistic regression will be provided. The results (comparison between the groups) will be presented as an Odds Ratio (OR) (and a two-sided 95% CI) and the trial will be deemed to have met its objective of non-inferiority if the lower bound of the CI (equivalent to a one-sided 97.5% CI) is above a critical value of 0.45 as described above. Secondary outcomes will be analysed using analogous models with logistic regression for binary endpoints, Cox regression for time-to-event endpoints and multiple linear regression for continuous endpoints. Where appropriate, repeated measures analyses will also be used. The tests will however be two-sided at 5%.