Single-cycle rituximab-induced immunologic changes in children: Enhanced in neuroimmunologic disease?

Angela Deyà-Martínez; Yadira Gordón; Cristina Molina-Anguita; Alexandru Vlagea; Monica Piquer; Manel Juan; Ana Esteve-Solé; Jordi Antón; Álvaro Madrid; Ana García-García; Ana M Plaza; Thaís Armangue; Laia Alsina

doi:10.1212/NXI.0000000000000724

Single-cycle rituximab-induced immunologic changes in children: Enhanced in neuroimmunologic disease?

Neurol Neuroimmunol Neuroinflamm. 2020 May 6;7(4):e724. doi: 10.1212/NXI.0000000000000724. Print 2020 Jul.

Affiliations

¹ From the Clinical Immunology and Primary Immunodeficiencies Unit (A.D.-M., A.E.-S., A.G.-G., L.A.), Pediatric Allergy and Clinical Immunology Department (A.D.-M., Y.G., M.P., A.E.-S., A.G.-G., A.M.P., L.A.), Hospital Sant Joan de Déu, Barcelona, Spain; Institut de Recerca Sant Joan de Déu (A.D.-M., Y.G., M.P., A.E.-S., J.A., A.G.-G., A.M.P., L.A.), Barcelona, Spain; Clinical Immunology Unit Hospital Sant Joan de Déu-Hospital Clínic (A.D.-M., A.V., M.P., M.J., A.E.-S., A.G.-G., A.M.P., L.A.), Barcelona, Spain; Universitat de Barcelona (J.A., L.A., M.J.), Spain; Immunology Department (A.V., M.J.), Biomedical Diagnostics Center, Hospital Clinic-IDIBAPS, Barcelona, Spain; Pediatric Neuroimmunology Unit (C.M.-A., T.A.), Neurology Department, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain; Neuroimmunology Program (T.A.), Institut D'Investigacions Biomèdiques (IDIBAPS), Hospital Clinic, University of Barcelona, Barcelona, Spain; Pediatric Rheumatology Division (J.A.), Hospital Sant Joan de Déu, Barcelona, Spain; and Pediatric Nephrology Department (Á.M.), Hospital Sant Joan de Déu, Barcelona, Spain.
² From the Clinical Immunology and Primary Immunodeficiencies Unit (A.D.-M., A.E.-S., A.G.-G., L.A.), Pediatric Allergy and Clinical Immunology Department (A.D.-M., Y.G., M.P., A.E.-S., A.G.-G., A.M.P., L.A.), Hospital Sant Joan de Déu, Barcelona, Spain; Institut de Recerca Sant Joan de Déu (A.D.-M., Y.G., M.P., A.E.-S., J.A., A.G.-G., A.M.P., L.A.), Barcelona, Spain; Clinical Immunology Unit Hospital Sant Joan de Déu-Hospital Clínic (A.D.-M., A.V., M.P., M.J., A.E.-S., A.G.-G., A.M.P., L.A.), Barcelona, Spain; Universitat de Barcelona (J.A., L.A., M.J.), Spain; Immunology Department (A.V., M.J.), Biomedical Diagnostics Center, Hospital Clinic-IDIBAPS, Barcelona, Spain; Pediatric Neuroimmunology Unit (C.M.-A., T.A.), Neurology Department, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain; Neuroimmunology Program (T.A.), Institut D'Investigacions Biomèdiques (IDIBAPS), Hospital Clinic, University of Barcelona, Barcelona, Spain; Pediatric Rheumatology Division (J.A.), Hospital Sant Joan de Déu, Barcelona, Spain; and Pediatric Nephrology Department (Á.M.), Hospital Sant Joan de Déu, Barcelona, Spain. [email protected] [email protected].

Abstract

Objective: To investigate the immunologic impact of a single cycle of rituximab (RTX) in children and adolescents with immune-mediated disorders, we evaluated B cells and immunoglobulin levels of 20 patients with neuroimmunologic, nephrologic, dermatologic, and rheumatologic disorders treated under recommended guidelines.

Methods: Retrospective study of immunologic changes in children (aged ≤18 years) diagnosed with immune-mediated disorders in which RTX was prescribed between June 2014 and February 2019. Patients were excluded if they had prior diagnosis of malignant disease or primary immunodeficiency. Patients were clinically and immunologically followed up every 3 months. Only patients having received a single cycle of RTX and with a follow-up greater than 12 months were included in the analysis of persistent dysgammaglobulinemia.

Results: Twenty children were included. Median age at RTX treatment was 12.8 years (interquartile range [IQR] 6.6-15.5 years). Median follow-up was 12.6 months (IQR 10.2-24 months). Of the 14 patients eligible for persistent dysgammaglobulinemia analysis (3 had received RTX retreatment, 2 had <12 months post-RTX follow-up, and in 1 data for this time point was missing), 2/14 (14%) remained with complete B-cell depletion, and 5/14 (36%) had dysgammaglobulinemia. Patients with dysgammaglobulinemia were younger (7.8 vs 15.6 years, p = 0.072), had more underlying neuroimmunologic diseases (5/5 vs 0/9, p < 0.001), and had received more frequently concentrated doses of RTX (3/5 vs 1/9, p = 0.05) than patients without dysgammaglobulinemia. Kinetics of immunoglobulins in the 20 patients revealed a decrease as early as 3 months after RTX in patients with neuroimmunologic disorders.

Conclusion: In our cohort, single-cycle RTX-induced dysgammaglobulinemia was enhanced in patients with neuroimmunologic diseases. Further studies are needed to confirm this observation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
B-Lymphocytes / drug effects*
Child
Child, Preschool
Dysgammaglobulinemia / chemically induced*
Female
Follow-Up Studies
Humans
Immune System Diseases / drug therapy*
Immunologic Factors / administration & dosage
Immunologic Factors / adverse effects*
Male
Retrospective Studies
Rituximab / administration & dosage
Rituximab / adverse effects*

Substances

Immunologic Factors
Rituximab