Rituximab-associated Hypogammaglobulinemia in pediatric patients with autoimmune diseases

Amer Mohammad Khojah*, Michael L Miller, Marisa S Klein-Gitelman, Megan L. Curran, Victoria Hans, Lauren M Pachman, Ramsay L Fuleihan

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Background: Despite the increased use of rituximab in treating pediatric patients with autoimmune diseases in the last decade, there are limited data on rituximab safety in those subjects who have a developing immune system. The objective of this study is to determine the prevalence of hypogammaglobulinemia in children with autoimmune disease receiving rituximab within the first three years of treatment in the pediatric rheumatology clinic at a tertiary care center. Methods: We conducted a retrospective chart review of 63 pediatric subjects who received rituximab for the treatment of their autoimmune disease. Immunoglobulin gamma (IgG) levels, immunosuppressive medication and the need for immunoglobulin replacement therapy were evaluated. Hypogammaglobulinemia was defined as a serum IgG level less than two standard deviations below the mean for age-matched healthy controls. Results: Twenty-eight patients (44%) were found to have hypogammaglobulinemia. Hypogammaglobulinemia occurred within the first six months of rituximab treatment in the majority of patients (22 out of 28). The occurrence of hypogammaglobulinemia varied based on the rituximab indication: 46% pediatric Systemic Lupus Erythematosus (SLE), 71% autoimmune CNS disease, 60% ANCA vasculitis, and 12% in the miscellaneous group. Autoimmune CNS disease had more severe hypogammaglobulinemia, more persistent and was associated with more frequent or severe infections. Three patients with autoimmune CNS disease and one with SLE were given IgG replacement therapy to prevent recurrent or severe infections. Conclusions: The prevalence of hypogammaglobulinemia in rituximab treated children with autoimmune disease seems to be higher than published data for adults, especially for children with autoimmune CNS disease. The onset of hypogammaglobulinemia is usually within six months of initiation of rituximab therapy. We recommend: 1) obtaining an IgG level prior to starting rituximab; 2) close monitoring for hypogammaglobulinemia after the use of rituximab in pediatric patients and 3) early institution of immunoglobulin replacement therapy if patients develop recurrent infections.

Original languageEnglish (US)
Article number61
JournalPediatric Rheumatology
Volume17
Issue number1
DOIs
StatePublished - Aug 28 2019
Externally publishedYes

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Agammaglobulinemia
Autoimmune Diseases
Pediatrics
Central Nervous System Diseases
Immunoglobulins
Passive Immunization
Systemic Lupus Erythematosus
Infection
Rituximab
Therapeutics
Antineutrophil Cytoplasmic Antibodies
Rheumatology
Immunosuppressive Agents
Vasculitis
Tertiary Care Centers
Immune System
Safety

Keywords

  • And ANCA vasculitis
  • Autoimmune CNS diseases
  • Hypogammaglobulinemia
  • Rituximab
  • SLE

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Rheumatology
  • Immunology and Allergy

Cite this

@article{9aa4d01b77774ce48cd9fcd7be36ab9d,
title = "Rituximab-associated Hypogammaglobulinemia in pediatric patients with autoimmune diseases",
abstract = "Background: Despite the increased use of rituximab in treating pediatric patients with autoimmune diseases in the last decade, there are limited data on rituximab safety in those subjects who have a developing immune system. The objective of this study is to determine the prevalence of hypogammaglobulinemia in children with autoimmune disease receiving rituximab within the first three years of treatment in the pediatric rheumatology clinic at a tertiary care center. Methods: We conducted a retrospective chart review of 63 pediatric subjects who received rituximab for the treatment of their autoimmune disease. Immunoglobulin gamma (IgG) levels, immunosuppressive medication and the need for immunoglobulin replacement therapy were evaluated. Hypogammaglobulinemia was defined as a serum IgG level less than two standard deviations below the mean for age-matched healthy controls. Results: Twenty-eight patients (44{\%}) were found to have hypogammaglobulinemia. Hypogammaglobulinemia occurred within the first six months of rituximab treatment in the majority of patients (22 out of 28). The occurrence of hypogammaglobulinemia varied based on the rituximab indication: 46{\%} pediatric Systemic Lupus Erythematosus (SLE), 71{\%} autoimmune CNS disease, 60{\%} ANCA vasculitis, and 12{\%} in the miscellaneous group. Autoimmune CNS disease had more severe hypogammaglobulinemia, more persistent and was associated with more frequent or severe infections. Three patients with autoimmune CNS disease and one with SLE were given IgG replacement therapy to prevent recurrent or severe infections. Conclusions: The prevalence of hypogammaglobulinemia in rituximab treated children with autoimmune disease seems to be higher than published data for adults, especially for children with autoimmune CNS disease. The onset of hypogammaglobulinemia is usually within six months of initiation of rituximab therapy. We recommend: 1) obtaining an IgG level prior to starting rituximab; 2) close monitoring for hypogammaglobulinemia after the use of rituximab in pediatric patients and 3) early institution of immunoglobulin replacement therapy if patients develop recurrent infections.",
keywords = "And ANCA vasculitis, Autoimmune CNS diseases, Hypogammaglobulinemia, Rituximab, SLE",
author = "Khojah, {Amer Mohammad} and Miller, {Michael L} and Klein-Gitelman, {Marisa S} and Curran, {Megan L.} and Victoria Hans and Pachman, {Lauren M} and Fuleihan, {Ramsay L}",
year = "2019",
month = "8",
day = "28",
doi = "10.1186/s12969-019-0365-y",
language = "English (US)",
volume = "17",
journal = "Pediatric Rheumatology",
issn = "1546-0096",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Rituximab-associated Hypogammaglobulinemia in pediatric patients with autoimmune diseases

AU - Khojah, Amer Mohammad

AU - Miller, Michael L

AU - Klein-Gitelman, Marisa S

AU - Curran, Megan L.

AU - Hans, Victoria

AU - Pachman, Lauren M

AU - Fuleihan, Ramsay L

PY - 2019/8/28

Y1 - 2019/8/28

N2 - Background: Despite the increased use of rituximab in treating pediatric patients with autoimmune diseases in the last decade, there are limited data on rituximab safety in those subjects who have a developing immune system. The objective of this study is to determine the prevalence of hypogammaglobulinemia in children with autoimmune disease receiving rituximab within the first three years of treatment in the pediatric rheumatology clinic at a tertiary care center. Methods: We conducted a retrospective chart review of 63 pediatric subjects who received rituximab for the treatment of their autoimmune disease. Immunoglobulin gamma (IgG) levels, immunosuppressive medication and the need for immunoglobulin replacement therapy were evaluated. Hypogammaglobulinemia was defined as a serum IgG level less than two standard deviations below the mean for age-matched healthy controls. Results: Twenty-eight patients (44%) were found to have hypogammaglobulinemia. Hypogammaglobulinemia occurred within the first six months of rituximab treatment in the majority of patients (22 out of 28). The occurrence of hypogammaglobulinemia varied based on the rituximab indication: 46% pediatric Systemic Lupus Erythematosus (SLE), 71% autoimmune CNS disease, 60% ANCA vasculitis, and 12% in the miscellaneous group. Autoimmune CNS disease had more severe hypogammaglobulinemia, more persistent and was associated with more frequent or severe infections. Three patients with autoimmune CNS disease and one with SLE were given IgG replacement therapy to prevent recurrent or severe infections. Conclusions: The prevalence of hypogammaglobulinemia in rituximab treated children with autoimmune disease seems to be higher than published data for adults, especially for children with autoimmune CNS disease. The onset of hypogammaglobulinemia is usually within six months of initiation of rituximab therapy. We recommend: 1) obtaining an IgG level prior to starting rituximab; 2) close monitoring for hypogammaglobulinemia after the use of rituximab in pediatric patients and 3) early institution of immunoglobulin replacement therapy if patients develop recurrent infections.

AB - Background: Despite the increased use of rituximab in treating pediatric patients with autoimmune diseases in the last decade, there are limited data on rituximab safety in those subjects who have a developing immune system. The objective of this study is to determine the prevalence of hypogammaglobulinemia in children with autoimmune disease receiving rituximab within the first three years of treatment in the pediatric rheumatology clinic at a tertiary care center. Methods: We conducted a retrospective chart review of 63 pediatric subjects who received rituximab for the treatment of their autoimmune disease. Immunoglobulin gamma (IgG) levels, immunosuppressive medication and the need for immunoglobulin replacement therapy were evaluated. Hypogammaglobulinemia was defined as a serum IgG level less than two standard deviations below the mean for age-matched healthy controls. Results: Twenty-eight patients (44%) were found to have hypogammaglobulinemia. Hypogammaglobulinemia occurred within the first six months of rituximab treatment in the majority of patients (22 out of 28). The occurrence of hypogammaglobulinemia varied based on the rituximab indication: 46% pediatric Systemic Lupus Erythematosus (SLE), 71% autoimmune CNS disease, 60% ANCA vasculitis, and 12% in the miscellaneous group. Autoimmune CNS disease had more severe hypogammaglobulinemia, more persistent and was associated with more frequent or severe infections. Three patients with autoimmune CNS disease and one with SLE were given IgG replacement therapy to prevent recurrent or severe infections. Conclusions: The prevalence of hypogammaglobulinemia in rituximab treated children with autoimmune disease seems to be higher than published data for adults, especially for children with autoimmune CNS disease. The onset of hypogammaglobulinemia is usually within six months of initiation of rituximab therapy. We recommend: 1) obtaining an IgG level prior to starting rituximab; 2) close monitoring for hypogammaglobulinemia after the use of rituximab in pediatric patients and 3) early institution of immunoglobulin replacement therapy if patients develop recurrent infections.

KW - And ANCA vasculitis

KW - Autoimmune CNS diseases

KW - Hypogammaglobulinemia

KW - Rituximab

KW - SLE

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