Original Title: Guides et normes: usage optimal des immunoglobulines en transplantation d’organes solides

Authors' objectives: Nonspecific human immunoglobulins (Igs) are stable products derived from human plasma. Their cost is high, their supply variable, and their use in Québec has been steadily increasing for many years in a number of areas of medicine, including solid organ transplantation. The framework for the use of nonspecific human immunoglobulins is therefore one of the concerns of Québec’s Comité consultatif national de médecine transfusionnelle, which has called attention to the lack of recommendations concerning their use for most solid organ transplantation indications. At the suggestion of the Comité consultatif national de médecine transfusionnelle, the Ministère de la Santé et des Services sociaux asked the Institut national d'excellence en santé et en services sociaux to develop clinical recommendations concerning the use of nonspecific human immunoglobulins in solid organ transplantation, in the form of an optimal use guide. At the completion of this project, INESSS had developed clinical recommendations for the optimal use of nonspecific human intravenous immunoglobulin (IVIg) in solid organ transplantation to prevent or treat eight different infections and to prevent or treat transplant rejection in pediatric or adult solid organ transplant recipients (kidney, heart, lung, liver, pancreas or small intestine).

Authors' results and conclusions: RESULTS: The systematic literature review indicates, with a level of evidence considered moderate to low, that IVIg is ineffective in preventing transplant rejection in solid organ transplant recipients. However, the clinical practice guidelines recommend the use of IVIg to prevent transplant rejection in transplant recipients in specific situations. The advisory committee’s members also indicated that IVIg could be considered a treatment option for preventing transplant rejection in hyperimmunized individuals or in cases of HLA- or ABO-incompatible transplants. In the case of liver transplantation, the committee members also indicated that IVIg could be considered a treatment option to prevent transplant rejection in HLA- or ABO-incompatible transplant recipients. However, there is insufficient data regarding the prevention of transplant rejection in hyperimmunized individuals who have received a liver transplant. The data from the systematic reviews indicate that IVIg is only marginally effective or ineffective for four indications: the prevention of Epstein-Barr virus infections (low level of evidence), the treatment of norovirus infections (low level of evidence), and the prevention and the treatment of polyomavirus BK infections (moderate to low level of evidence). In addition, the systematic literature reviews did not yield any primary studies and have an insufficient level of evidence to draw any conclusions regarding the treatment of Epstein-Barr virus infections or the prevention of norovirus infections. The clinical practice guideline recommendations and the clinician perspective are consistent in not recommending the use of IVIg to prevent Epstein-Barr virus, norovirus or BK polyomavirus infections, or to treat Epstein-Barr virus or norovirus infections. Nevertheless, the experts consulted indicated that IVIg may be considered a treatment option for treating confirmed polyomavirus BK nephropathy in solid organ transplant recipients, particularly if concurrent transplant rejection is suspected in a kidney transplant recipient. CONCLUSIONS: Evidence on the efficacy data of Igs was available for a minority of the indications of interest, and the level of evidence was considered low or insufficient for 17 of these 18 indications. An assessment of the scientific and contextual data and the clinician perspective led to the following conclusions: • the Institut national d'excellence en santé et en services sociaux recommends that IVIg be considered a treatment option, a second-line treatment or, in specific situations, for the treatment of transplant rejection or the prevention of transplant rejection under specific conditions of use in solid organ transplant recipients, and for the treatment of parvovirus B19 or polyomavirus BK infections in solid organ transplant recipients; • the Institut national d'excellence en santé et en services sociaux does not recommend the use of IVIg to prevent Epstein-Barr virus, norovirus, HHV-6, parvovirus B19, polyomavirus BK, adenovirus, or West Nile virus infections or to treat of Epstein-Barr virus, norovirus or HHV-6 infections in solid organ transplant recipients.

Authors' recommendations: Because of insufficient data, the Institut national d'excellence en santé et en services sociaux could not make recommendations concerning the use of IVIg to prevent transplant rejection in hyperimmunized individuals who have received a liver transplant, to treat chronic humoral rejection in solid organ transplant recipients, to prevent respiratory syncytial virus infections or to treat respiratory syncytial virus, adenovirus or West Nile virus infections in solid organ transplant recipients. The use of IVIg may be associated with transfusion reactions, which are usually not serious. Serious transfusion reactions, which are rare, have, however, been reported. In conclusion, the recommendations in the optimal use guide on nonspecific human immunoglobulins in solid organ transplantation are in addition to those in the previous guides for neurology, hematology, clinical immunology, dermatology, rheumatology, and infectious diseases, which are intended to reduce the inappropriate use of this resource.

Authors' methods: In response to the mandate from the Ministère de la Santé et des Services sociaux, the Institut national d'excellence en santé et en services sociaux used a collaborative approach known as “knowledge mobilization”. This approach consists of analyzing and assessing scientific and contextual data as well as the perspectives of clinicians. (1. Scientific data) - To assess the efficacy and safety of Igs in children and adults for each of the selected solid organ transplantation indications, we conducted a systematic review for each one in several bibliographic databases from the date of their inception to June 2021 to identify all the primary studies and systematic reviews with a meta-analysis published on the subject. The official product monographs for Health Canada-approved Igs, Health Canada and U.S. Food and Drug Administration advisories, and a transfusion accident and incident report published by the Institut national de santé publique du Québec were consulted to complete the search concerning safety. (2. Contextual data and the clinician perspective) -The number of persons treated and the quantity (expressed in grams) of Igs administered in Québec in 2018 and 2019 were documented from a report on their use prepared by the Institut national de santé publique du Québec using information extracted from the TraceLine™ system database. Health Canada’s website was consulted to check the approval status of IVIg. (3. Process of constructing recommendations) - The analysis and synthesis of the scientific and contextual data as well as the clinician perspective enabled structuring of the arguments leading to the formulation of the recommendations. Only those recommendations for which there was a consensus among the experts were retained. The solid organ transplantation indications for preventing or treating eight different infections and for preventing or treating transplant rejection in pediatric or adult solid organ transplant recipients (kidney, heart, lung, liver, pancreas or small intestine) were divided into four use categories: IVIg recommended, IVIg a possible treatment option, IVIg not recommended, and insufficient data.

Project Status: Completed

URL for project: https://www.inesss.qc.ca/en/publications/publications/publication/usage-optimal-des-immunoglobulines-en-transplantation-dorganes-solides.html

Year Published: 2022

URL for published report: https://www.inesss.qc.ca/en/publications/publications/publication/usage-optimal-des-immunoglobulines-en-transplantation-dorganes-solides.html

English language abstract: An English language summary is available

Publication Type: Other

Country: Canada

Province: Quebec

Organisation Name: Institut national d'excellence en sante et en services sociaux

Contact Address: L'Institut national d'excellence en sante et en services sociaux (INESSS) , 2021, avenue Union, bureau 10.083, Montreal, Quebec, Canada, H3A 2S9;Tel: 1+514-873-2563, Fax: 1+514-873-1369

Contact Name: demande@inesss.qc.ca

Contact Email: demande@inesss.qc.ca

Copyright: Gouvernement du Québec