Eugene Yu-Hin Chan1,2,3, Ellen L M Yu4, Andrea Angeletti5,6, Zainab Arslan3, Biswanath Basu7, Olivia Boyer8, Chang-Yien Chan9,10, Manuela Colucci11, Guillaume Dorval8, Claire Dossier12, Stefania Drovandi5, Gian Marco Ghiggeri5, Debbie S Gipson13, Riku Hamada14, Julien Hogan15, Kenji Ishikura16,17, Koichi Kamei18, Markus J Kemper19, Alison Lap-Tak Ma20,2, Rulan S Parekh21, Seetha Radhakrishnan21, Priya Saini21, Qian Shen22, Rajiv Sinha23, Chantida Subun3, Sharon Teo10, Marina Vivarelli24, Hazel Webb3, Hong Xu22, Hui Kim Yap9,10, Kjell Tullus25. 1. Paediatric Nephrology Centre, Hong Kong Children's Hospital, Hong Kong SAR eugene.chan@ha.org.hk Kjell.Tullus@gosh.nhs.uk. 2. Department of Paediatrics and Adolescent Medicine, University of Hong Kong, Hong Kong SAR. 3. Department of Paediatric Nephrology, Great Ormond Street Hospital for Children, National Health Service Trust, London, United Kingdom. 4. Clinical Research Center, Princess Margaret Hospital, Hong Kong SAR. 5. Nephrology, Dialysis and Transplantation, IRCCS Istituto Giannina Gaslini, Genoa, Italy. 6. Laboratory of Molecular Nephrology, IRCCS Istituto Giannina Gaslini, Genova, Italy. 7. Division of Pediatric Nephrology, Nilratan Sircar Medical College and Hospital, Kolkata, India. 8. Pediatric Nephrology, Reference Center for Nephrotic Syndrome in Children and Adults, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Institut Imagine, Institut National de la Santé et de la Recherche Médicale (INSERM) U1163, Université Paris Cité, Paris, France. 9. Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. 10. Khoo Teck Puat - National University Children's Medical Institute, National University Health System, Singapore. 11. Renal Diseases Research Unit, Genetics and Rare Diseases Research Division, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy. 12. Pediatric Nephrology Department, Robert Debré Hospital, APHP, Paris, France. 13. Division of Nephrology, Department of Pediatrics, University of Michigan, CS Mott Children's Hospital, Ann Arbor, Michigan. 14. Department of Nephrology and Rheumatology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan. 15. Department of Pediatric Nephrology, Robert-Debré Hospital, Reference Center for Nephrotic Syndrome in Children and Adults, Centre de Référence Syndrome Néphrotique de l'Enfant et de l'Adulte (CMR SNI), AP-HP, Université Paris Cité, Paris, France. 16. Department of Pediatrics, Kitasato University School of Medicine, Tokyo, Japan. 17. Department of Pediatrics, Kitasato University Hospital, Tokyo, Japan. 18. Division of Nephrology and Rheumatology, National Center for Child Health and Development, Tokyo, Japan. 19. Department of Pediatrics, Asklepios Medical School, Hamburg, Germany. 20. Paediatric Nephrology Centre, Hong Kong Children's Hospital, Hong Kong SAR. 21. Division of Pediatric Nephrology, Hospital for Sick Children, Toronto, Ontario, Canada. 22. Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China. 23. Pediatric Nephrology Unit, Institute of Child Health, Kolkata, India. 24. Division of Nephrology, Department of Pediatric Subspecialties, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy. 25. Department of Paediatric Nephrology, Great Ormond Street Hospital for Children, National Health Service Trust, London, United Kingdom eugene.chan@ha.org.hk Kjell.Tullus@gosh.nhs.uk.
Abstract
BACKGROUND: Long-term outcomes after multiple courses of rituximab among children with frequently relapsing, steroid-dependent nephrotic syndrome (FRSDNS) are unknown. METHODS: A retrospective cohort study at 16 pediatric nephrology centers from ten countries in Asia, Europe, and North America included children with FRSDNS who received two or more courses of rituximab. Primary outcomes were relapse-free survival and adverse events. RESULTS: A total of 346 children (age, 9.8 years; IQR, 6.6-13.5 years; 73% boys) received 1149 courses of rituximab. A total of 145, 83, 50, 28, 22, and 18 children received two, three, four, five, six, and seven or more courses, respectively. Median (IQR) follow-up was 5.9 (4.3-7.7) years. Relapse-free survival differed by treatment courses (clustered log-rank test P<0.001). Compared with the first course (10.0 months; 95% CI, 9.0 to 10.7 months), relapse-free period and relapse risk progressively improved after subsequent courses (12.0-16.0 months; HRadj, 0.03-0.13; 95% CI, 0.01 to 0.18; P<0.001). The duration of B-cell depletion remained similar with repeated treatments (6.1 months; 95% CI, 6.0 to 6.3 months). Adverse events were mostly mild; the most common adverse events were hypogammaglobulinemia (50.9%), infection (4.5%), and neutropenia (3.7%). Side effects did not increase with more treatment courses nor a higher cumulative dose. Only 78 of the 353 episodes of hypogammaglobulinemia were clinically significant. Younger age at presentation (2.8 versus 3.3 years; P=0.05), age at first rituximab treatment (8.0 versus 10.0 years; P=0.01), and history of steroid resistance (28% versus 18%; P=0.01) were associated with significant hypogammaglobulinemia. All 53 infective episodes resolved, except for one patient with hepatitis B infection and another with EBV infection. There were 42 episodes of neutropenia, associated with history of steroid resistance (30% versus 20%; P=0.04). Upon last follow-up, 332 children (96%) had normal kidney function. CONCLUSIONS: Children receiving repeated courses of rituximab for FRSDNS experience an improving clinical response. Side effects appear acceptable, but significant complications can occur. These findings support repeated rituximab use in FRSDNS.
BACKGROUND: Long-term outcomes after multiple courses of rituximab among children with frequently relapsing, steroid-dependent nephrotic syndrome (FRSDNS) are unknown. METHODS: A retrospective cohort study at 16 pediatric nephrology centers from ten countries in Asia, Europe, and North America included children with FRSDNS who received two or more courses of rituximab. Primary outcomes were relapse-free survival and adverse events. RESULTS: A total of 346 children (age, 9.8 years; IQR, 6.6-13.5 years; 73% boys) received 1149 courses of rituximab. A total of 145, 83, 50, 28, 22, and 18 children received two, three, four, five, six, and seven or more courses, respectively. Median (IQR) follow-up was 5.9 (4.3-7.7) years. Relapse-free survival differed by treatment courses (clustered log-rank test P<0.001). Compared with the first course (10.0 months; 95% CI, 9.0 to 10.7 months), relapse-free period and relapse risk progressively improved after subsequent courses (12.0-16.0 months; HRadj, 0.03-0.13; 95% CI, 0.01 to 0.18; P<0.001). The duration of B-cell depletion remained similar with repeated treatments (6.1 months; 95% CI, 6.0 to 6.3 months). Adverse events were mostly mild; the most common adverse events were hypogammaglobulinemia (50.9%), infection (4.5%), and neutropenia (3.7%). Side effects did not increase with more treatment courses nor a higher cumulative dose. Only 78 of the 353 episodes of hypogammaglobulinemia were clinically significant. Younger age at presentation (2.8 versus 3.3 years; P=0.05), age at first rituximab treatment (8.0 versus 10.0 years; P=0.01), and history of steroid resistance (28% versus 18%; P=0.01) were associated with significant hypogammaglobulinemia. All 53 infective episodes resolved, except for one patient with hepatitis B infection and another with EBV infection. There were 42 episodes of neutropenia, associated with history of steroid resistance (30% versus 20%; P=0.04). Upon last follow-up, 332 children (96%) had normal kidney function. CONCLUSIONS: Children receiving repeated courses of rituximab for FRSDNS experience an improving clinical response. Side effects appear acceptable, but significant complications can occur. These findings support repeated rituximab use in FRSDNS.
Authors: Piero Ruggenenti; Barbara Ruggiero; Paolo Cravedi; Marina Vivarelli; Laura Massella; Maddalena Marasà; Antonietta Chianca; Nadia Rubis; Bogdan Ene-Iordache; Michael Rudnicki; Rosa Maria Pollastro; Giovambattista Capasso; Antonio Pisani; Marco Pennesi; Francesco Emma; Giuseppe Remuzzi Journal: J Am Soc Nephrol Date: 2014-01-30 Impact factor: 10.121
Authors: L Peuvrel; A Chiffoleau; G Quéreux; A Brocard; M Saint-Jean; A Batz; P Jolliet; B Dréno Journal: Dermatology Date: 2013-07-09 Impact factor: 5.366