Kazumoto Iijima1,2, Mayumi Sako3, Mari Oba4, Seiji Tanaka5, Riku Hamada6, Tomoyuki Sakai7, Yoko Ohwada8, Takeshi Ninchoji9, Tomohiko Yamamura9, Hiroyuki Machida10, Yuko Shima11, Ryojiro Tanaka12, Hiroshi Kaito9,12, Yoshinori Araki13, Tamaki Morohashi14, Naonori Kumagai15, Yoshimitsu Gotoh16, Yohei Ikezumi17, Takuo Kubota18, Koichi Kamei19, Naoya Fujita20, Yasufumi Ohtsuka21, Takayuki Okamoto22, Takeshi Yamada23, Eriko Tanaka24, Masaki Shimizu25, Tomoko Horinouchi9, Akihide Konishi26, Takashi Omori26, Koichi Nakanishi27, Kenji Ishikura28, Shuichi Ito10, Hidefumi Nakamura29, Kandai Nozu9. 1. Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan iijima@med.kobe-u.ac.jp kdiijima_kch@hp.pref.hyogo.jp. 2. Hyogo Prefectural Kobe Children's Hospital, Kobe, Japan. 3. Department of Clinical Research Promotion, National Center for Child Health and Development, Tokyo, Japan. 4. Department of Medical Statistics, Toho University, Tokyo, Japan. 5. Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan. 6. Department of Nephrology, Tokyo Metropolitan Children's Medical Center, Fuchu, Japan. 7. Department of Pediatrics, Shiga University of Medical Science, Otsu, Japan. 8. Department of Pediatrics, Dokkyo Medical University School of Medicine, Mibu, Japan. 9. Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan. 10. Department of Pediatrics, Yokohama City University, Yokohama, Japan. 11. Department of Pediatrics, Wakayama Medical University, Wakayama City, Japan. 12. Department of Nephrology, Hyogo Prefectural Kobe Children's Hospital, Kobe, Japan. 13. Department of Pediatrics, National Hospital Organization Hokkaido Medical Center, Sapporo, Japan. 14. Department of Pediatrics, Nihon University School of Medicine, Tokyo, Japan. 15. Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Japan. 16. Department of Pediatrics, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Japan. 17. Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Japan. 18. Department of Pediatrics, Osaka University, Suita, Japan. 19. Division of Nephrology and Rheumatology, National Center for Child Health and Development, Tokyo, Japan. 20. Department of Nephrology, Aichi Children's Health and Medical Center, Obu, Japan. 21. Department of Pediatrics, Saga University, Saga City, Japan. 22. Department of Pediatrics, Hokkaido University Hospital, Sapporo, Japan. 23. Department of Pediatrics, Niigata University Medical and Dental Hospital, Niigata City, Japan. 24. Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan. 25. Department of Pediatrics, Kanazawa University, Kanazawa, Japan. 26. Clinical and Translational Research Center, Kobe University Hospital, Kobe, Japan. 27. Department of Child Health and Welfare (Pediatrics), Graduate School of Medicine, University of the Ryukyus, Nishihara, Japan. 28. Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Japan. 29. Department of Research and Development Supervision, Clinical Research Center, National Center for Child Health and Development, Tokyo, Japan.
Abstract
BACKGROUND: Rituximab is the standard therapy for childhood-onset complicated frequently relapsing or steroid-dependent nephrotic syndrome (FRNS/SDNS). However, most patients redevelop FRNS/SDNS after peripheral B cell recovery. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled trial to examine whether mycophenolate mofetil (MMF) administration after rituximab can prevent treatment failure (FRNS, SDNS, steroid resistance, or use of immunosuppressive agents or rituximab). In total, 39 patients (per group) were treated with rituximab, followed by either MMF or placebo until day 505 (treatment period). The primary outcome was time to treatment failure (TTF) throughout the treatment and follow-up periods (until day 505 for the last enrolled patient). RESULTS: TTFs were clinically but not statistically significantly longer among patients given MMF after rituximab than among patients receiving rituximab monotherapy (median, 784.0 versus 472.5 days, hazard ratio [HR], 0.59; 95% confidence interval [95% CI], 0.34 to 1.05, log-rank test: P=0.07). Because most patients in the MMF group presented with treatment failure after MMF discontinuation, we performed a post-hoc analysis limited to the treatment period and found that MMF after rituximab prolonged the TTF and decreased the risk of treatment failure by 80% (HR, 0.20; 95% CI, 0.08 to 0.50). Moreover, MMF after rituximab reduced the relapse rate and daily steroid dose during the treatment period by 74% and 57%, respectively. The frequency and severity of adverse events were similar in both groups. CONCLUSIONS: Administration of MMF after rituximab may sufficiently prevent the development of treatment failure and is well tolerated, although the relapse-preventing effect disappears after MMF discontinuation.
BACKGROUND: Rituximab is the standard therapy for childhood-onset complicated frequently relapsing or steroid-dependent nephrotic syndrome (FRNS/SDNS). However, most patients redevelop FRNS/SDNS after peripheral B cell recovery. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled trial to examine whether mycophenolate mofetil (MMF) administration after rituximab can prevent treatment failure (FRNS, SDNS, steroid resistance, or use of immunosuppressive agents or rituximab). In total, 39 patients (per group) were treated with rituximab, followed by either MMF or placebo until day 505 (treatment period). The primary outcome was time to treatment failure (TTF) throughout the treatment and follow-up periods (until day 505 for the last enrolled patient). RESULTS: TTFs were clinically but not statistically significantly longer among patients given MMF after rituximab than among patients receiving rituximab monotherapy (median, 784.0 versus 472.5 days, hazard ratio [HR], 0.59; 95% confidence interval [95% CI], 0.34 to 1.05, log-rank test: P=0.07). Because most patients in the MMF group presented with treatment failure after MMF discontinuation, we performed a post-hoc analysis limited to the treatment period and found that MMF after rituximab prolonged the TTF and decreased the risk of treatment failure by 80% (HR, 0.20; 95% CI, 0.08 to 0.50). Moreover, MMF after rituximab reduced the relapse rate and daily steroid dose during the treatment period by 74% and 57%, respectively. The frequency and severity of adverse events were similar in both groups. CONCLUSIONS: Administration of MMF after rituximab may sufficiently prevent the development of treatment failure and is well tolerated, although the relapse-preventing effect disappears after MMF discontinuation.
Authors: Gina-Marie Barletta; William E Smoyer; Timothy E Bunchman; Joseph T Flynn; David B Kershaw Journal: Pediatr Nephrol Date: 2003-05-28 Impact factor: 3.714
Authors: Martina Tedesco; Federica Mescia; Isabella Pisani; Marco Allinovi; Giovanni Casazza; Lucia Del Vecchio; Marisa Santostefano; Luigi Cirillo; Francesca Ferrario; Ciro Esposito; Pasquale Esposito; Domenico Santoro; Roberta Lazzarin; Giovanni Maria Rossi; Enrico Fiaccadori; Angelo Ferrantelli; Renato Alberto Sinico; Mario Cozzolino; Maurizio Gallieni; Lino Cirami; Francesco Scolari; Augusto Vaglio; Federico Alberici Journal: Kidney Int Rep Date: 2022-05-30