Long-term outcome of childhood-onset complicated nephrotic syndrome after a multicenter, double-blind, randomized, placebo-controlled trial of rituximab

• Published in: Pediatric nephrology (Berlin, West) West), 2017-11, Vol.32 (11), p.2071-2078
• Main Authors: Kamei, Koichi, Ishikura, Kenji, Sako, Mayumi, Aya, Kunihiko, Tanaka, Ryojiro, Nozu, Kandai, Kaito, Hiroshi, Nakanishi, Koichi, Ohtomo, Yoshiyuki, Miura, Kenichiro, Takahashi, Shori, Morimoto, Tetsuji, Kubota, Wataru, Ito, Shuichi, Nakamura, Hidefumi, Iijima, Kazumoto
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Body height; Breath tests; Child; Child, Preschool; Childhood; Children; Clinical trials; Double-Blind Method; Double-blind studies; Drug therapy; Female; Follow-Up Studies; Humans; Immunologic Factors - adverse effects; Immunologic Factors - therapeutic use; Immunosuppressive agents; Immunosuppressive Agents - administration & dosage; Immunotherapy; Inhibitor drugs; Kidney diseases; Liver; Lymphocytes B; Male; Medicine; Medicine & Public Health; Monoclonal antibodies; Nephrology; Nephrotic syndrome; Nephrotic Syndrome - complications; Nephrotic Syndrome - drug therapy; Original Article; Patient outcomes; Pediatric diseases; Pediatrics; Prospective Studies; Recurrence; Remission; Renal function; Renal insufficiency; Retrospective Studies; Rituximab; Rituximab - adverse effects; Rituximab - therapeutic use; Survival Analysis; Toxicity; Treatment Outcome; Urology; Young Adult
• ISSN: 0931-041X; 1432-198X
• DOI: 10.1007/s00467-017-3718-0

Background Although rituximab effectively prevents relapses of complicated frequently relapsing nephrotic syndrome (FRNS) and steroid-dependent nephrotic syndrome (SDNS), data of long-term outcomes and safety are limited. Methods Fifty-one patients (age, 3–38 years) with childhood-onset complicated FRNS or SDNS, who received rituximab in investigator-initiated multicenter prospective trials were enrolled. Rituximab was administered at 375 mg/m 2 once weekly for 4 weeks, and immunosuppressive agents were discontinued according to the study protocol. We investigated relapses, re-administration of immunosuppressive agents, additional rituximab treatment, body height, renal function, and late adverse events during the observation period. Results Forty-eight patients (94%) developed relapses during the observation period (median, 59 months) and the 50% relapse-free survival was 261 days. Thirty patients (59%) developed SDNS, 44 (86%) required re-administration of immunosuppressive agents, and 22 (43%) received additional rituximab treatment. All patients who were receiving immunosuppressive agents at rituximab treatment required either immunosuppressive agents or additional rituximab treatment. On the contrary, 5 of the 13 patients without immunosuppressive agents at rituximab treatment required neither immunosuppressive agents nor additional rituximab treatment and 3 of them did not develop relapse during observation period. Growth failure due to steroid toxicity did not progress and none of the patients developed chronic renal insufficiency. None of the patients suffered from rituximab-related late adverse events. Conclusions As most patients suffer from relapses after B-cell recovery, long-term immunosuppressive agents or additional rituximab treatment is necessary. However, some patients who can discontinue immunosuppressive agents before rituximab treatment may achieve long-term remission after rituximab treatment without immunosuppressive agents.