Audit of immunoglobulin monitoring and hypogammaglobulinaemia after B cell targeted therapy in a paediatric cohort in a high immune disease prevalence Region

Introduction: Secondary hypogammaglobulinaemia or antibody deficiency (SAD) is an under-recognised complication of B cell-targeted therapies (BCTTs) in both autoimmune diseases (AIDs) and haematological malignancy. In 2019, UK recommendations were published for SAD in patients receiving BCTT,1 while...

Full description

Saved in:
Bibliographic Details
Main Authors: Khadija Karim, Omar Mostafa, Alaa Samarh, Sharon Bout-Tabaku, Buthaina Al-Adba, Ahmad Kaddourah, Abubakr Imam, Ibrahim Shatat, Bajes Hamad, Mahmoud Fawzi, Ruba Benini, Ayman Saleh, Tayseer Yousif, Areeg Ahmed, Yasmin El Bsat, Bernice Lo, Mohammed Yousuf Karim
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:Clinical Medicine
Online Access:http://www.sciencedirect.com/science/article/pii/S1470211825000855
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850071221865021440
author Khadija Karim
Omar Mostafa
Alaa Samarh
Sharon Bout-Tabaku
Buthaina Al-Adba
Ahmad Kaddourah
Abubakr Imam
Ibrahim Shatat
Bajes Hamad
Mahmoud Fawzi
Ruba Benini
Ayman Saleh
Tayseer Yousif
Areeg Ahmed
Yasmin El Bsat
Bernice Lo
Mohammed Yousuf Karim
author_facet Khadija Karim
Omar Mostafa
Alaa Samarh
Sharon Bout-Tabaku
Buthaina Al-Adba
Ahmad Kaddourah
Abubakr Imam
Ibrahim Shatat
Bajes Hamad
Mahmoud Fawzi
Ruba Benini
Ayman Saleh
Tayseer Yousif
Areeg Ahmed
Yasmin El Bsat
Bernice Lo
Mohammed Yousuf Karim
author_sort Khadija Karim
collection DOAJ
description Introduction: Secondary hypogammaglobulinaemia or antibody deficiency (SAD) is an under-recognised complication of B cell-targeted therapies (BCTTs) in both autoimmune diseases (AIDs) and haematological malignancy. In 2019, UK recommendations were published for SAD in patients receiving BCTT,1 while, in 2022, the American Academy of Allergy, Asthma, and Immunology (AAAAI) produced guidance.2 Both publications recommend baseline immunoglobulin (Ig) measurements, followed by at 6–12-monthly intervals. Aims: Our aims here were to (1) describe Ig monitoring in our paediatric cohort receiving BCTT; and (2) audit our practice as per the 2019 UK and 2022 AAAAI guidance. Materials and Methods: Pharmacy records were screened for AID and malignancy patients receiving BCTT at Sidra Medicine between 2016 and 2024. Patients were between 0 and 18 years of age at the time of starting BCTT. Frequency and results of Ig testing were extracted from electronic medical records. These findings were audited against monitoring guidance from the 2019 and 2022 publications. Hypogammaglobulinaemia was defined as IgG below the lower limit of age-related reference range (irrespective of IgA and IgM levels). Values of IgG and the prevalence of hypogammaglobulinaemia were recorded at baseline and during follow-up. Results and Discussion: 98 patients were identified and 92 included with a minimum of 6 months’ follow-up duration (Fig 1); • Pre-BCTT baseline IgG results were available in 82/92 patients (89.1%); • 19/82 patients (23.2%) had low IgG levels at baseline; • 73/92 patients (79.3%) had IgG testing post-BCTTs; • Range of IgG measurements per patient: 1–14 timepoints over median follow-up of 0–72 months.Baseline IgG tests were almost always performed as per the guidance (Table 1). Baseline IgG was low in 23.2% patients, confirming the importance of this timepoint. However, post-BCTT IgG monitoring followed the guidance less strictly. Only 79.3% of patients had IgG measured post-BCTT, with variation in monitoring between specialties. Adherence to guidance was relatively lower in patients seen under neurology and nephrology. One systemic lupus erythematous (SLE) patient developed persistent low IgG after a solitary BCTT cycle. Further testing revealed an underlying primary immune deficiency disorder/inborn error of immunity. Conclusion: Baseline IgG tests were almost always performed as per the guidance, illustrating close adherence by clinicians. Furthermore, baseline IgG was low in 23.2% of patients, showing the clinical importance of baseline measurements, otherwise, low IgG during follow-up might be incorrectly attributed to BCTT. However, IgG measurement post-BCTT did not follow the guidance as closely. Overall, only 79.3% of patients had IgG measured post-BCTT, with clear variation in monitoring between specialties: haematology/oncology and rheumatology showed closer adherence compared with neurology and nephrology. The importance of baseline testing and monitoring was demonstrated by unmasking of a primary immune deficiency disorder in an SLE patient after a solitary BCTT cycle.3 Recommendations: (1) Protocol-driven approach to standardise IgG collection timepoints and improve monitoring; (2) Automation of IgG monitoring by including IgG orders as part of combined pharmacy–pathology rituximab order set; (3) Clinical Immunology review if persistent antibody deficiency and/or recurrent/severe infections develop after BCTT.
format Article
id doaj-art-ff97b076bfc749f9b46511f84958c41b
institution DOAJ
issn 1470-2118
language English
publishDate 2025-07-01
publisher Elsevier
record_format Article
series Clinical Medicine
spelling doaj-art-ff97b076bfc749f9b46511f84958c41b2025-08-20T02:47:21ZengElsevierClinical Medicine1470-21182025-07-0125410036710.1016/j.clinme.2025.100367Audit of immunoglobulin monitoring and hypogammaglobulinaemia after B cell targeted therapy in a paediatric cohort in a high immune disease prevalence RegionKhadija Karim0Omar Mostafa1Alaa Samarh2Sharon Bout-Tabaku3Buthaina Al-Adba4Ahmad Kaddourah5Abubakr Imam6Ibrahim Shatat7Bajes Hamad8Mahmoud Fawzi9Ruba Benini10Ayman Saleh11Tayseer Yousif12Areeg Ahmed13Yasmin El Bsat14Bernice Lo15Mohammed Yousuf Karim16King's College LondonSidra MedicineSidra MedicineSidra MedicineSidra MedicineSidra MedicineSidra MedicineSidra MedicineSidra MedicineSidra MedicineSidra MedicineSidra MedicineSidra MedicineSidra MedicineSidra MedicineSidra MedicineSidra MedicineIntroduction: Secondary hypogammaglobulinaemia or antibody deficiency (SAD) is an under-recognised complication of B cell-targeted therapies (BCTTs) in both autoimmune diseases (AIDs) and haematological malignancy. In 2019, UK recommendations were published for SAD in patients receiving BCTT,1 while, in 2022, the American Academy of Allergy, Asthma, and Immunology (AAAAI) produced guidance.2 Both publications recommend baseline immunoglobulin (Ig) measurements, followed by at 6–12-monthly intervals. Aims: Our aims here were to (1) describe Ig monitoring in our paediatric cohort receiving BCTT; and (2) audit our practice as per the 2019 UK and 2022 AAAAI guidance. Materials and Methods: Pharmacy records were screened for AID and malignancy patients receiving BCTT at Sidra Medicine between 2016 and 2024. Patients were between 0 and 18 years of age at the time of starting BCTT. Frequency and results of Ig testing were extracted from electronic medical records. These findings were audited against monitoring guidance from the 2019 and 2022 publications. Hypogammaglobulinaemia was defined as IgG below the lower limit of age-related reference range (irrespective of IgA and IgM levels). Values of IgG and the prevalence of hypogammaglobulinaemia were recorded at baseline and during follow-up. Results and Discussion: 98 patients were identified and 92 included with a minimum of 6 months’ follow-up duration (Fig 1); • Pre-BCTT baseline IgG results were available in 82/92 patients (89.1%); • 19/82 patients (23.2%) had low IgG levels at baseline; • 73/92 patients (79.3%) had IgG testing post-BCTTs; • Range of IgG measurements per patient: 1–14 timepoints over median follow-up of 0–72 months.Baseline IgG tests were almost always performed as per the guidance (Table 1). Baseline IgG was low in 23.2% patients, confirming the importance of this timepoint. However, post-BCTT IgG monitoring followed the guidance less strictly. Only 79.3% of patients had IgG measured post-BCTT, with variation in monitoring between specialties. Adherence to guidance was relatively lower in patients seen under neurology and nephrology. One systemic lupus erythematous (SLE) patient developed persistent low IgG after a solitary BCTT cycle. Further testing revealed an underlying primary immune deficiency disorder/inborn error of immunity. Conclusion: Baseline IgG tests were almost always performed as per the guidance, illustrating close adherence by clinicians. Furthermore, baseline IgG was low in 23.2% of patients, showing the clinical importance of baseline measurements, otherwise, low IgG during follow-up might be incorrectly attributed to BCTT. However, IgG measurement post-BCTT did not follow the guidance as closely. Overall, only 79.3% of patients had IgG measured post-BCTT, with clear variation in monitoring between specialties: haematology/oncology and rheumatology showed closer adherence compared with neurology and nephrology. The importance of baseline testing and monitoring was demonstrated by unmasking of a primary immune deficiency disorder in an SLE patient after a solitary BCTT cycle.3 Recommendations: (1) Protocol-driven approach to standardise IgG collection timepoints and improve monitoring; (2) Automation of IgG monitoring by including IgG orders as part of combined pharmacy–pathology rituximab order set; (3) Clinical Immunology review if persistent antibody deficiency and/or recurrent/severe infections develop after BCTT.http://www.sciencedirect.com/science/article/pii/S1470211825000855
spellingShingle Khadija Karim
Omar Mostafa
Alaa Samarh
Sharon Bout-Tabaku
Buthaina Al-Adba
Ahmad Kaddourah
Abubakr Imam
Ibrahim Shatat
Bajes Hamad
Mahmoud Fawzi
Ruba Benini
Ayman Saleh
Tayseer Yousif
Areeg Ahmed
Yasmin El Bsat
Bernice Lo
Mohammed Yousuf Karim
Audit of immunoglobulin monitoring and hypogammaglobulinaemia after B cell targeted therapy in a paediatric cohort in a high immune disease prevalence Region
Clinical Medicine
title Audit of immunoglobulin monitoring and hypogammaglobulinaemia after B cell targeted therapy in a paediatric cohort in a high immune disease prevalence Region
title_full Audit of immunoglobulin monitoring and hypogammaglobulinaemia after B cell targeted therapy in a paediatric cohort in a high immune disease prevalence Region
title_fullStr Audit of immunoglobulin monitoring and hypogammaglobulinaemia after B cell targeted therapy in a paediatric cohort in a high immune disease prevalence Region
title_full_unstemmed Audit of immunoglobulin monitoring and hypogammaglobulinaemia after B cell targeted therapy in a paediatric cohort in a high immune disease prevalence Region
title_short Audit of immunoglobulin monitoring and hypogammaglobulinaemia after B cell targeted therapy in a paediatric cohort in a high immune disease prevalence Region
title_sort audit of immunoglobulin monitoring and hypogammaglobulinaemia after b cell targeted therapy in a paediatric cohort in a high immune disease prevalence region
url http://www.sciencedirect.com/science/article/pii/S1470211825000855
work_keys_str_mv AT khadijakarim auditofimmunoglobulinmonitoringandhypogammaglobulinaemiaafterbcelltargetedtherapyinapaediatriccohortinahighimmunediseaseprevalenceregion
AT omarmostafa auditofimmunoglobulinmonitoringandhypogammaglobulinaemiaafterbcelltargetedtherapyinapaediatriccohortinahighimmunediseaseprevalenceregion
AT alaasamarh auditofimmunoglobulinmonitoringandhypogammaglobulinaemiaafterbcelltargetedtherapyinapaediatriccohortinahighimmunediseaseprevalenceregion
AT sharonbouttabaku auditofimmunoglobulinmonitoringandhypogammaglobulinaemiaafterbcelltargetedtherapyinapaediatriccohortinahighimmunediseaseprevalenceregion
AT buthainaaladba auditofimmunoglobulinmonitoringandhypogammaglobulinaemiaafterbcelltargetedtherapyinapaediatriccohortinahighimmunediseaseprevalenceregion
AT ahmadkaddourah auditofimmunoglobulinmonitoringandhypogammaglobulinaemiaafterbcelltargetedtherapyinapaediatriccohortinahighimmunediseaseprevalenceregion
AT abubakrimam auditofimmunoglobulinmonitoringandhypogammaglobulinaemiaafterbcelltargetedtherapyinapaediatriccohortinahighimmunediseaseprevalenceregion
AT ibrahimshatat auditofimmunoglobulinmonitoringandhypogammaglobulinaemiaafterbcelltargetedtherapyinapaediatriccohortinahighimmunediseaseprevalenceregion
AT bajeshamad auditofimmunoglobulinmonitoringandhypogammaglobulinaemiaafterbcelltargetedtherapyinapaediatriccohortinahighimmunediseaseprevalenceregion
AT mahmoudfawzi auditofimmunoglobulinmonitoringandhypogammaglobulinaemiaafterbcelltargetedtherapyinapaediatriccohortinahighimmunediseaseprevalenceregion
AT rubabenini auditofimmunoglobulinmonitoringandhypogammaglobulinaemiaafterbcelltargetedtherapyinapaediatriccohortinahighimmunediseaseprevalenceregion
AT aymansaleh auditofimmunoglobulinmonitoringandhypogammaglobulinaemiaafterbcelltargetedtherapyinapaediatriccohortinahighimmunediseaseprevalenceregion
AT tayseeryousif auditofimmunoglobulinmonitoringandhypogammaglobulinaemiaafterbcelltargetedtherapyinapaediatriccohortinahighimmunediseaseprevalenceregion
AT areegahmed auditofimmunoglobulinmonitoringandhypogammaglobulinaemiaafterbcelltargetedtherapyinapaediatriccohortinahighimmunediseaseprevalenceregion
AT yasminelbsat auditofimmunoglobulinmonitoringandhypogammaglobulinaemiaafterbcelltargetedtherapyinapaediatriccohortinahighimmunediseaseprevalenceregion
AT bernicelo auditofimmunoglobulinmonitoringandhypogammaglobulinaemiaafterbcelltargetedtherapyinapaediatriccohortinahighimmunediseaseprevalenceregion
AT mohammedyousufkarim auditofimmunoglobulinmonitoringandhypogammaglobulinaemiaafterbcelltargetedtherapyinapaediatriccohortinahighimmunediseaseprevalenceregion