KEY POINTS: Fifty-five percent of patients achieve long-term remission after rituximab treatment. This is influenced by maintenance therapy with rituximab. A substantial reduction of annualized relapse rate and concomitant immunosuppression was observed after rituximab treatment. BACKGROUND: Long-term outcomes of rituximab-treated adult patients with podocytopathies (either minimal change disease or FSGS) are largely unknown. METHODS: A retrospective study at 30 nephrology departments from 15 countries worldwide included rituximab-treated adults with primary podocytopathies and a minimum clinical follow-up of 36 months. The primary outcome was relapse-free survival at 36 months. RESULTS: One hundred eighty-three adult patients (n=64 with FSGS and n=119 with minimal change disease) with difficult-to-treat nephrotic syndrome (68% steroid-dependent/frequently relapsing, 22% steroid-resistant, 85% previously treated with two or more lines of immunosuppressive therapy) were treated with rituximab as part of a remission induction regimen. Complete or partial remission at 6 months after rituximab treatment was achieved in 82%. Eighty-three of 151 (55%) initial responders achieved long-term relapse-free survival over 3 years. Maintenance therapy with rituximab was associated with a better relapse-free survival (hazard ratio, 2.05; 95% confidence interval [CI], 1.07 to 3.91), irrespective of the dosing regimen. At 36 months, 61% of initial responders receiving maintenance therapy with rituximab achieved long-term relapse-free survival and withdrawal of all concomitant immunosuppressive medication compared with 36% of patients without maintenance treatment (odds ratio, 2.69; 95% CI, 1.27 to 5.73). Relapses per year were reduced from an annual relapse rate of 1.0 (95% CI, 1.0 to 1.7) before to 0.17 (95% CI, 0.00 to 0.24) relapses per year after rituximab initiation. Over the 36 months of follow-up, a stable course of eGFR was observed in those who initially responded with either complete or partial remission, whereas nonresponders experienced a reduction in eGFR reaching −11 (95% CI, −18 to −8) ml/min per 1.73 m2. CONCLUSIONS: Rituximab facilitated achievement of initial and long-term response in a majority of adult patients with difficult-to-treat podocytopathies. Maintenance treatment with rituximab was further associated with long-term relapse-free survival over 3 years. Nonresponse to initial rituximab treatment was associated with poor kidney prognosis.

1st Department of Nephrology School of Medicine Hippokration General Hospital Aristotle University of Thessaloniki Thessaloniki Greece

Clinic of Nephrology and Renal Transplantation Laiko General Hospital Athens Greece

Complex Glomerular Disease Unit Nephrology and Renal Transplant Department Hospital Clinic Barcelona IDIBAPS University of Barcelona Barcelona Spain

Département de Néphrologie et Transplantation d'Organes Centre de Référence des Maladies Rénales Rares Centre Hospitalier Universitaire de Toulouse Toulouse France

Department of Biostatistics and Translational Medicine Medical University of Lodz Lodz Poland

Department of Cardiovascular Sciences University of Leicester Leicester United Kingdom

Department of Health Medicine and Caring Sciences Linköping University Linköping Sweden

Department of Internal Diseases Nephrology and Dialysis Military Institute of Medicine National Research Institute Warsaw Poland

Department of Internal Medicine 3 Division of Nephrology Friedrich Schiller University University Hospital Jena Jena Germany

Department of Internal Medicine 4 Klinikum Wels Grieskirchen Wels Austria

Department of Internal Medicine 4 Medical University Innsbruck Innsbruck Austria

Department of Medical and Surgical Specialities Radiological Sciences and Public Health University of Brescia Brescia Italy

Department of Nephrology 1st Faculty of Medicine Charles University and General University Hospital Prague Prague Czech Republic

Department of Nephrology and Dialysis Dubrava University Hospital Zagreb Croatia

Department of Nephrology and Kidney Transplantation University Hospital of Patras Patras Greece

Department of Nephrology and Transplantation Rare French Disease Centre Idiopathic Nephrotic syndrome Henri Mondor Hospital University Hopital Assistance Publique Hôpitaux de Paris Inserm U955 Team 21 Paris East University Créteil France

Department of Nephrology Complejo Hospitalario de Navarra Navarra Spain

Department of Nephrology Facultad de Medicina Hospital Clínico San Carlos Universidad Complutense Madrid Spain

Department of Nephrology Hospital de Clínicas Dr Manuel Quintela Universidad de la República Montevideo Uruguay

Department of Nephrology Hospital Universitario 12 de Octubre Madrid Spain

Department of Nephrology Hospital Universitario La Paz Institutito de Investigacion IdiPaz Madrid Spain

Department of Nephrology Postgraduate Institute of Medical Education and Research Chandigarh India

Department of Nephrology University Hospital of Wales Cardiff United Kingdom

Department of Renal Medicine CLINTEC Karolinska Institutet at Karolinska University Hospital Stockholm Sweden

Division of Nephrology Columbia University Medical Center New York New York

Division of Nephrology Department of Internal Medicine Istanbul Faculty of Medicine Istanbul University Istanbul Turkey

Division of Nephrology Department of Internal Medicine Medical University of Graz Graz Austria

Division of Nephrology Department of Internal Medicine Necmettin Erbakan University Konya Turkey

Division of Nephrology Department of Medicine 4 LMU University Hospital LMU Munich Munich Germany

EpiDermE Epidemiology in Dermatology and Evaluation of Therapeutics EA7379 Paris Est Créteil University UPEC Créteil France

Faculty of Pharmacy and Biochemistry University of Zagreb Zagreb Croatia

Fédération Hospitalo Universitaire TRUE InnovaTive theRapy for immUne disordErs Assistance Publique Hôpitaux de Paris Henri Mondor Hospital Créteil France

INSERM Centre d'Investigation Clinique 1430 Créteil France

Institut National de la Santé et de la Recherche Médicale U1297 et Faculté de Médecine Université Toulouse 3 Toulouse France

Institute of Immunology and Immunotherapy University of Birmingham Birmingham United Kingdom

John Walls Renal Unit University Hospitals of Leicester NHS Trust Leicester United Kingdom

Nephrology Department Fundación Puigvert Autónoma de Barcelona University Barcelona Spain

Nephrology Unit ASST Spedali Civili di Brescia Brescia Italy

School of Medicine University of Zagreb Zagreb Croatia

Tareev Clinic of Internal Diseases Sechenov 1st Moscow State Medical University Moscow Russia

University College London Department of Renal Medicine Royal Free Hospital London United Kingdom

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