The effect of rituximab therapy on immunoglobulin levels in patients with multisystem autoimmune disease

Rituximab is a B cell depleting anti-CD20 monoclonal antibody. CD20 is not expressed on mature plasma cells and accordingly rituximab does not have immediate effects on immunoglobulin levels. However, after rituximab some patients develop hypogammaglobulinaemia. We performed a single centre retrospe...

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Veröffentlicht in:BMC musculoskeletal disorders 2014-05, Vol.15 (1), p.178-178, Article 178
Hauptverfasser: Marco, Helena, Smith, Rona M, Jones, Rachel B, Guerry, Mary-Jane, Catapano, Fausta, Burns, Stella, Chaudhry, Afzal N, Smith, Kenneth G C, Jayne, David R W
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container_end_page 178
container_issue 1
container_start_page 178
container_title BMC musculoskeletal disorders
container_volume 15
creator Marco, Helena
Smith, Rona M
Jones, Rachel B
Guerry, Mary-Jane
Catapano, Fausta
Burns, Stella
Chaudhry, Afzal N
Smith, Kenneth G C
Jayne, David R W
description Rituximab is a B cell depleting anti-CD20 monoclonal antibody. CD20 is not expressed on mature plasma cells and accordingly rituximab does not have immediate effects on immunoglobulin levels. However, after rituximab some patients develop hypogammaglobulinaemia. We performed a single centre retrospective review of 177 patients with multisystem autoimmune disease receiving rituximab between 2002 and 2010. The incidence, severity and complications of hypogammaglobulinaemia were investigated. Median rituximab dose was 6 g (1-20.2) and total follow-up was 8012 patient-months. At first rituximab, the proportion of patients with IgG
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CD20 is not expressed on mature plasma cells and accordingly rituximab does not have immediate effects on immunoglobulin levels. However, after rituximab some patients develop hypogammaglobulinaemia. We performed a single centre retrospective review of 177 patients with multisystem autoimmune disease receiving rituximab between 2002 and 2010. The incidence, severity and complications of hypogammaglobulinaemia were investigated. Median rituximab dose was 6 g (1-20.2) and total follow-up was 8012 patient-months. At first rituximab, the proportion of patients with IgG &lt;6 g/L was 13% and remained stable at 17% at 24 months and 14% at 60 months. Following rituximab, 61/177 patients (34%) had IgG &lt;6 g/L for at least three consecutive months, of whom 7/177 (4%) had IgG &lt;3 g/L. Low immunoglobulin levels were associated with higher glucocorticoid doses during follow up and there was a trend for median IgG levels to fall after ≥ 6 g rituximab. 45/115 (39%) with IgG ≥ 6 g/L versus 26/62 (42%) with IgG &lt;6 g/L experienced severe infections (p=0.750). 6/177 patients (3%) received intravenous immunoglobulin replacement therapy, all with IgG &lt;5 g/L and recurrent infection. In multi-system autoimmune disease, prior cyclophosphamide exposure and glucocorticoid therapy but not cumulative rituximab dose was associated with an increased incidence of hypogammaglobulinaemia. Severe infections were common but were not associated with immunoglobulin levels. Repeat dose rituximab therapy appears safe with judicious monitoring.</description><identifier>ISSN: 1471-2474</identifier><identifier>EISSN: 1471-2474</identifier><identifier>DOI: 10.1186/1471-2474-15-178</identifier><identifier>PMID: 24884562</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Adolescent ; Adult ; Agammaglobulinemia - blood ; Agammaglobulinemia - chemically induced ; Agammaglobulinemia - diagnosis ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal, Murine-Derived - adverse effects ; Antibodies, Monoclonal, Murine-Derived - therapeutic use ; Autoimmune diseases ; Autoimmune Diseases - blood ; Autoimmune Diseases - diagnosis ; Autoimmune Diseases - drug therapy ; Care and treatment ; Complications and side effects ; Drug therapy ; Female ; Follow-Up Studies ; Humans ; Immune system ; Immunoglobulins - blood ; Immunologic Factors - adverse effects ; Immunologic Factors - therapeutic use ; Lupus ; Lymphoma ; Male ; Measurement ; Middle Aged ; Retrospective Studies ; Rituximab ; Treatment Outcome ; Young Adult</subject><ispartof>BMC musculoskeletal disorders, 2014-05, Vol.15 (1), p.178-178, Article 178</ispartof><rights>COPYRIGHT 2014 BioMed Central Ltd.</rights><rights>2014 Marco et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.</rights><rights>Copyright © 2014 Marco et al.; licensee BioMed Central Ltd. 2014 Marco et al.; licensee BioMed Central Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b584t-2212daa574afd50400801d8748db66946c953e75385cf069c8e1768b18cbca753</citedby><cites>FETCH-LOGICAL-b584t-2212daa574afd50400801d8748db66946c953e75385cf069c8e1768b18cbca753</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038057/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038057/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,729,782,786,866,887,27931,27932,53798,53800</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24884562$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Marco, Helena</creatorcontrib><creatorcontrib>Smith, Rona M</creatorcontrib><creatorcontrib>Jones, Rachel B</creatorcontrib><creatorcontrib>Guerry, Mary-Jane</creatorcontrib><creatorcontrib>Catapano, Fausta</creatorcontrib><creatorcontrib>Burns, Stella</creatorcontrib><creatorcontrib>Chaudhry, Afzal N</creatorcontrib><creatorcontrib>Smith, Kenneth G C</creatorcontrib><creatorcontrib>Jayne, David R W</creatorcontrib><title>The effect of rituximab therapy on immunoglobulin levels in patients with multisystem autoimmune disease</title><title>BMC musculoskeletal disorders</title><addtitle>BMC Musculoskelet Disord</addtitle><description>Rituximab is a B cell depleting anti-CD20 monoclonal antibody. CD20 is not expressed on mature plasma cells and accordingly rituximab does not have immediate effects on immunoglobulin levels. However, after rituximab some patients develop hypogammaglobulinaemia. We performed a single centre retrospective review of 177 patients with multisystem autoimmune disease receiving rituximab between 2002 and 2010. The incidence, severity and complications of hypogammaglobulinaemia were investigated. Median rituximab dose was 6 g (1-20.2) and total follow-up was 8012 patient-months. At first rituximab, the proportion of patients with IgG &lt;6 g/L was 13% and remained stable at 17% at 24 months and 14% at 60 months. Following rituximab, 61/177 patients (34%) had IgG &lt;6 g/L for at least three consecutive months, of whom 7/177 (4%) had IgG &lt;3 g/L. Low immunoglobulin levels were associated with higher glucocorticoid doses during follow up and there was a trend for median IgG levels to fall after ≥ 6 g rituximab. 45/115 (39%) with IgG ≥ 6 g/L versus 26/62 (42%) with IgG &lt;6 g/L experienced severe infections (p=0.750). 6/177 patients (3%) received intravenous immunoglobulin replacement therapy, all with IgG &lt;5 g/L and recurrent infection. In multi-system autoimmune disease, prior cyclophosphamide exposure and glucocorticoid therapy but not cumulative rituximab dose was associated with an increased incidence of hypogammaglobulinaemia. Severe infections were common but were not associated with immunoglobulin levels. 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CD20 is not expressed on mature plasma cells and accordingly rituximab does not have immediate effects on immunoglobulin levels. However, after rituximab some patients develop hypogammaglobulinaemia. We performed a single centre retrospective review of 177 patients with multisystem autoimmune disease receiving rituximab between 2002 and 2010. The incidence, severity and complications of hypogammaglobulinaemia were investigated. Median rituximab dose was 6 g (1-20.2) and total follow-up was 8012 patient-months. At first rituximab, the proportion of patients with IgG &lt;6 g/L was 13% and remained stable at 17% at 24 months and 14% at 60 months. Following rituximab, 61/177 patients (34%) had IgG &lt;6 g/L for at least three consecutive months, of whom 7/177 (4%) had IgG &lt;3 g/L. Low immunoglobulin levels were associated with higher glucocorticoid doses during follow up and there was a trend for median IgG levels to fall after ≥ 6 g rituximab. 45/115 (39%) with IgG ≥ 6 g/L versus 26/62 (42%) with IgG &lt;6 g/L experienced severe infections (p=0.750). 6/177 patients (3%) received intravenous immunoglobulin replacement therapy, all with IgG &lt;5 g/L and recurrent infection. In multi-system autoimmune disease, prior cyclophosphamide exposure and glucocorticoid therapy but not cumulative rituximab dose was associated with an increased incidence of hypogammaglobulinaemia. Severe infections were common but were not associated with immunoglobulin levels. Repeat dose rituximab therapy appears safe with judicious monitoring.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>24884562</pmid><doi>10.1186/1471-2474-15-178</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record>
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subjects Adolescent
Adult
Agammaglobulinemia - blood
Agammaglobulinemia - chemically induced
Agammaglobulinemia - diagnosis
Aged
Aged, 80 and over
Antibodies, Monoclonal, Murine-Derived - adverse effects
Antibodies, Monoclonal, Murine-Derived - therapeutic use
Autoimmune diseases
Autoimmune Diseases - blood
Autoimmune Diseases - diagnosis
Autoimmune Diseases - drug therapy
Care and treatment
Complications and side effects
Drug therapy
Female
Follow-Up Studies
Humans
Immune system
Immunoglobulins - blood
Immunologic Factors - adverse effects
Immunologic Factors - therapeutic use
Lupus
Lymphoma
Male
Measurement
Middle Aged
Retrospective Studies
Rituximab
Treatment Outcome
Young Adult
title The effect of rituximab therapy on immunoglobulin levels in patients with multisystem autoimmune disease
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