Original Title: Avis: transplantation des îlots de Langerhans chez les personnes atteintes d’un diabète de type 1 instable

Authors' objectives: This procedure is available in the United States, Australia, Europe and Asia on an experimental and nonexperimental basis. In Canada, it is performed in Edmonton and Vancouver in clinical programs and in Montréal (McGill University Health Centre [MUHC]) on an experimental basis. Given that the MUHC has acquired IT facilities and expertise, it is seeking designation as a supraregional centre specializing in this area. In this report, the Institut national d’excellence en santé et en services sociaux (INESSS) assesses the relevance of including IT in the range of treatments available to T1D patients.

Authors' results and conclusions: RESULTS: (EFFICACY) IT improves glycemic control in terms of the HbA1c concentration and the resolution of severe hypoglycemic episodes in both uremic and nonuremic patients (low to moderate level of evidence). The proportion of completely or partially functional grafts is very mixed. The best 5-year outcomes vary from 70 to 80% (per-protocol analysis). IT results in a lower rate and duration of insulin independence than PT. Both uremic and nonuremic patients who require insulin therapy after IT nonetheless maintain optimal glycemic control, that is, an HbA1c concentration ≤ 7%, and are protected against severe hypoglycemic episodes. Few studies have evaluated the efficacy of IT in preventing, in the medium or long term, the complications associated with T1D (cardiovascular disease, nephropathy, retinopathy and neuropathy), and the available data are inconclusive (very low level of evidence). (SAFETY) The data from indirect comparison studies indicate that IT is associated with a lower risk of complications than PT (low level of evidence). Certain complications are resolved surgically or medically (laparotomies, transfusions). Other adverse events resolve spontaneously (transient elevation of liver enzyme levels, minor bleeding). The frequency of adverse events related to immunosuppression varies. The serious adverse events (nephrotoxicity, cancer) can lead to discontinuation of the immunosuppression and, ultimately, to the loss of the graft. (PATIENT PERSPECTIVE) The need for information to make an informed decision varies according to the patient. Patients hope to become insulin-independent with IT, even if it is only for a brief period of time, and they want to improve their well-being and energy level. Patients report an improvement in their quality of life after IT (low level of evidence). Indeed, they tend to have greater well-being, a greater functional capacity and fewer short-term depressive symptoms. Their social life tends to improve for a certain amount of time, and they are generally satisfied with the procedure.  The patients consulted indicated that their level of satisfaction with their treatment varies, whether it was multiple-injection insulin therapy, insulin pump therapy or IT. Some patients entertain unrealistic hopes about IT. Specifically, they believe that it can cure their diabetes. The main factors that influence their decision are the stage of the disease, the risk/clinical benefit ratio, and the support from their family and friends. Most patients say that they prefer IT to PT because they find it less risky. (ECONOMIC DATA) The economic analyses indicate that IT is not a cost-effective option compared to intensive insulin therapy because of the high cost of islet isolation. When compared to PT, IT would, however, be acceptable. The cost-effectiveness of ITcompared to that of the usual treatments is uncertain, given the low level of evidence. A cost analysis conducted over a 3-year time horizon from the perspective of the Ministère de la Santé et des Services sociaux (MSSS) indicates that the average cost of IT per patient varies from $99,000 to $132,000 when 10 patients undergo an average of 2 ILTs. The average cost of IT increases by approximately 25% if only 5 patients are treated per year. (ETHICAL CONSIDERATIONS)  To be eligible for IT, patients with T1D should first have to exhaust all the other available treatment options, including the insulin pump and continuous blood glucose monitoring. In Québec, these treatment modalities are not accessible to all patients, which poses a problem, both from an ethical and clinical standpoint.

Authors' recommendations: Recommendation 1 INESSS recommends granting public coverage of IT to patients with T1D who, despite optimal management, have reached a therapeutic dead end. These are patients with severe glycemic lability that is not due to a behavioural cause, but that is associated with severe, recurrent hypoglycemic episodes - that require a third person’s intervention or hospitalization - that are not perceived and that cannot be prevented despite appropriate intensive insulin therapy. Recommendation 2 INESSS recommends that the relevance of covering a continuous blood glucose monitoring system and the insulin pump be assessed for patients who meet the eligibility criteria for IT or PT. Recommendation 3 INESSS recommends that a provincial multidisciplinary committee be formed that would be charged mainly with ensuring patient selection according to established criteria and ensuring that the program’s performance is monitored. Recommendation 4 INESSS recommends that the IT eligibility criteria be reviewed periodically in light of the new available evidence. The relevance of using IT should be reassessed in light of the new available treatments. Recommendation 5 INESSS recommends that the offer of IT be evaluated in a real-world healthcare setting. An evaluation report should be submitted each year to the institution’s Council of Physicians, Dentists and Pharmacists and to the MSSS. The following clinical indicators should be documented in that report: graft survival rate; number of IT per patient; pre- and post-IT HbA1c concentration; pre- and post-IT severe hypoglycemic episode rate; insulin independence rate; safety of immunosuppression (infection rate, glomerular filtration rate); cost per patient. Recommendation 6 INESSS recommends that a shared-decision support tool be developed for IT-eligible patients so that they can make an informed decision. The tool should indicate: the different options that might be proposed to the patient, including that of not doing anything; the benefits, uncertainties and risks associated with each option. Recommendation 7 INESSS recommends that steps be taken toward a pan-Canadian consultation regarding the offer of IT and that the roles and complementarities of the different IT referral centres in Canada be defined.

Authors' methods: A systematic literature review was conducted to document the efficacy, safety and cost-effectiveness of IT. In addition, an examination of the patients’ perspective, whether or not they had undergone IT, was performed based on an exhaustive literature review and interviews with patients. The ethical considerations were examined by means of a narrative review. The costs associated with IT are presented, as are contextual data from the grey literature and consultations with healthcare professionals.

Project Status: Completed

URL for project: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/transplantation-des-ilots-de-langerhans-chez-les-personnes-atteintes-dun-diabete-de-type-1-instable.html

Year Published: 2018

URL for published report: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/transplantation-des-ilots-de-langerhans-chez-les-personnes-atteintes-dun-diabete-de-type-1-instable.html

English language abstract: An English language summary is available

Publication Type: Full HTA

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