Management of perioperative iron deficiency anemia as part of patient blood management in France: A budget impact model-based analysis based on real world data.

OBJECTIVES: Patient Blood Management (PBM) is defined as a patient-centered, systematic, evidence-based approach to improve patient outcomes by managing and preserving a patient's own blood, while promoting patient safety and empowerment. As a corollary, it also reduces the utilization of allogeneic blood components. However, demonstrating cost-effectiveness depends on the health insurance system considered. This analysis aims to estimate the one-year budget impact of PBM in four elective surgical areas, from French National Health Insurance and hospital perspectives. METHODS: A budget impact model was developed to estimate the difference in the cost of care between scenarios with and without PBM. The impact of hematopoiesis optimization (first pillar of PBM) was studied throughout the management of preoperative anemia and iron deficiency in four types of surgeries: orthopedic, cardiac & cardiovascular, vascular & thoracic, and urologic & visceral surgery. Estimation of model's parameters was based on data collected in 10 French hospitals, literature, and on data from the French national medico-administrative database. RESULTS: A total of 980,125 patients were modeled for all four therapeutic areas. Results shows that implementation of a PBM program could generate annual savings up to €1079 M from the French National Health Insurance perspective (€1018 M from the hospital perspective), and the sparing of 181,451 red blood cells units per year. The deterministic sensitivity analysis showed that PBM generates savings for both perspectives in most parameters tested. CONCLUSION: Implementing PBM programs could result in important savings for the health care system in France.

[Assessment of the budgetary impact of an emicizumab therapy introduction for patients with severe haemophilia A without inhibitor]. / Évaluation de l'impact budgétaire de l'introduction d'un traitement par émicizumab chez des patients atteints d'hémophilie A sévère congénitale sans inhibiteur.

Since March 2019, émicizumab is indicated for the treatment of patients with severe haemophilia A without inhibitor. This therapy's price amounts approximately to €33 600 per 4 weeks for a 70kg patient which represents about two times more than a factor VIII concentrates treatment's price. This study aims to assess the budgetary impact for the French Health Insurance of an émicizumab therapy introduction for patients with severe haemophilia A without inhibitor. It was an observational, retrospective, and monocentric study. Every severe haemophilia A without inhibitor patient over 18 years old followed at the Cochin Hospital haemophilia treatment centre who received émicizumab from June 2020 and for at least one year have been included. The budgetary impact was estimated by comparing the total costs of patient care the year before versus the year after émicizumab initiation. Total costs of patient care included prices of i) treatments consumed, ii) consultations with specialist physicians, iii) hospitalizations and iv) imaging procedures. Thirty-eight patients were included. The total cost of patient care increased significantly the year after émicizumab introduction (P < 0.0001). On average, this cost was estimated at €537 887 ± €137 139 per patient whereas it was at €151 442 ± €94 708 the year before. While costs of physician consultations increased, no significant difference has been reported about hospitalizations and imaging costs. Over a one-year period, émicizumab therapy significantly increased the total costs of patient care. It is mostly caused by the drug price itself.

[Security of supply: Getting to know more about the organization of suppliers]. / Sécurité d'approvisionnement : mieux connaître l'organisation des fournisseurs.

OBJECTIVES: The worsening pharmaceutical products shortage required the central purchasing structure of AP-HP to include a new criterion on supply safety in the tenders' procedures. Each provider answering to the tender needs to complete a dedicated form. The aim is to review the collected information and assess its relevance. METHODS: This study is based on a retrospective analysis conducted on the last 2 tenders' procedures forms (one started in September 2019 and the other in February 2020). RESULTS: These 2 tenders' procedures were composed of 155 lots. The form response rate was 81,4%. The average rating on 20 was 10,9±3,8. The rates could be very variable depending on the lots. Regarding the 2020s tenders procedures, 57.8% of specialties were classified as drugs of major therapeutic interest. A shortage management plan exists for 24.0% of them. Providers indicated several sources of raw materials (36,1%) and several factories (35,5%). The average advanced stock was 4.1±3.8 months in France and 2.3±2.6 months in Europe. The information system implemented by suppliers scored an average of 15 out of 20. CONCLUSIONS: This study allowed us to know better the suppliers' organisation. The concerning points are the low stocks and the discrepancies in the suppliers' drugs of major therapeutic interest classification of a same product and the existence of a shortage management plan. This form will be maintained with more specific questions. An assessment will be done to determine the relevance of this form to prevent disruptions.

[Hybrid medicines in France. Hybrid medicines: Genesis and legal framework in Europe and in France]. / Les médicaments hybrides en France. Genèse des médicaments hybrides et cadre règlementaire en Europe et en France.

Hybrid medicines are defined as medicines that do not fill generic medicines' definition, forming a medicines group that stands half-way between reference medicinal products and generic medicines. The term "hybrid" was introduced in France in 2018, but the concept has existed for some fifteen years in Community legislation. The aim of this work is to expose hybrid medicines' legal framework, in Europe and in France. Hybrid medicines' European legal framework specifies in a guide of the European Medicines Agency, marketing authorization procedures that can be used for hybrid medicines, and what is required for marketing authorization applications. In France, a register of hybrid medicines' groups has been created, and registration procedures were specified in a decree at the end of 2019. Legal texts also underlined that substitution within hybrid medicines' group would be possible for some specific medical cases. Decrees specifying hybrid medicines' groups list and specific medical cases allowing substitution, are not appeared yet at the end of February 2021. Moreover, some elements have never been raised, particularly medical and economic assessment modalities.

[Hybrid medicines in France. Hybrid medicines: Overviews in France and in Paris Public Hospitals]. / Les médicaments hybrides en France. État des lieux des médicaments hybrides en France et à l'Assistance Publique­Hôpitaux de Paris.

OBJECTIVES: The aim of this study is to give an overview of hybrid medicines, term introduced in France by the Social Security Financing Act for 2019, with special attention to those available in Paris Public Hospitals (AP-HP), and to analyze their therapeutic values and economic issues. METHODS: Research by keywords on European and French health authorities' websites was done to provide a list of hybrid medicines. Then, an analysis of their profile and of their differences from reference medicinal products was done. A reflection on hybrid medicines likeness to "new medicines" or to "generic medicines" was carried out. Lastly, their therapeutic interests, their risks and their costs were assessed. RESULTS: In France 85 hybrid medicines were identified, including 41 commercialized, and 21 available in AP-HP. Six different types of differences from the reference medicinal product were found out. Over 90% of hybrid medicines show at least one interest compared to the reference medicines, even if it is not a major innovation. However, more than a third of hybrid medicines are associated to a risk in case of drug substitution with the reference medicinal product. Hybrid medicines costs appear to be lower than reference medicines, but with smaller discounts than what is usually observed with generic medicines. CONCLUSION: Hybrid medicines constitute a very heterogeneous population, whether in terms of differences from reference medicines, of interests or risks. Common rules development for all hybrid medicines may be complex and would require taking every couple hybrid/reference medicines specificities into account.

[Comparative analysis of the financing of follow-up and rehabilitation care institutions and public mental health institutions: Application for innovative and expensive drugs]. / Analyse comparative du financement des établissements de soins de suite et réadaptation et des établissements publics de santé mentale : application pour les médicaments innovants et onéreux.

Pharmacotherapeutic care is now expanding in public mental health institutions. Annual grants are funding the public psychiatric field, hindering access to therapeutic innovation and expensive medications due to long length of stay. On the threshold of the French Healthcare & Social Services Ministry "Ma Santé 2022" plan ("My Health 2022"), there is a risk of altering the continuum of care because of the complexity of the financing of certain high added value therapies. Despite a desire to adapt the system to meet constantly changing health needs, no actions have been taken to this date in psychiatry, with no funds being allocated for valuable medication, in contrary to follow-up care and rehabilitation structures, to our knowledge. This reinforces the discrepancy with the evolution of research, and further widens the gap in inequalities between health sectors. Optimising the funding of expensive medicines in psychiatry would make it possible to reduce the stranglehold of current allocations. Following the example of recent reforms in the follow-up care and rehabilitation structures, extra funds for high value-added therapies would make it possible to reduce complex medical decisions: from prevention to reintegration, patient care continuity would be vastly guaranteed.

[Health technology assessment of innovative medical devices: Timing and decision at national and local level]. / Accès au marché des dispositifs médicaux innovants : articulation entre évaluations nationales et hospitalières.

INTRODUCTION: The Medical Device Committee (CODIMS) evaluates all innovative medical devices (MD) before their introduction in the hospitals of the Assistance publique-hôpitaux de Paris (AP-HP). At the national level, the Medical Device and Health Technology Evaluation Committee (CNEDiMTS) provides recommendation for MD with respects to reimbursement by the National Health Insurance Fund. The aim of this study is to compare the recommendations of both committees and to analyze their timing on a six-year period. MATERIAL AND METHOD: We selected all innovative MD assessed by the CODIMS between 2013 and 2018. We retrieved all the recommendations for these MD from the CNEDiMTS. We performed quantitative and qualitative analysis of data collected. RESULTS: On 30 innovative MD assessed by both the CODIMS and the CNEDiMTS, 11 (37%) evaluations were performed by the CODIMS before the CNEDiMTS evaluation. They occurred approximately a year before the CNEDiMTS recommendation (an average of 378 days). Among the 25 MD with a recommendation of both committees, the two opinions were consistent in 88 per cent of all cases. DISCUSSION/CONCLUSION: This study highlights that there is a good consistency between the recommendations of both committees. This suggests that the MD evaluations conducted at the hospital level are relevant and timely. Finally, a better coordination between the national and local levels should be promoted for the MD assessment.

[Assessment of the use by hospital pharmacists of the opinions issued by the Haute Autorité de santé and the economic analysis tools proposed to them]. / Évaluation de l'utilisation par les pharmaciens hospitaliers des avis émis par la Haute Autorité de santé et des outils économiques qui leur sont proposés.

BACKGROUND: In French hospitals, the supply and management of drugs are missions of pharmacists. The aim of this study is to assess the use of efficacy and economics opinions of the Haute Autorite de santé (HAS) in hospital referencing of drugs in France in 2017. METHODS: A questionnaire for hospital pharmacists was developed to establish their knowledge and their uses of Transparency Commission and Economic and Public Health Evaluation Committee opinions. This survey was distributed by the ADIPH association in July 2017. This questionnaire included 35 questions. RESULTS: Despite the health professional are more and more interesting by economics analysis, only 30 % of hospitals pharmacists of this panel declared to use HAS economic opinions (versus 80% for Transparency Commission opinions). Among these pharmacists, 86% used this report in the hospital referencing of drugs. CONCLUSION: Through this analysis, some prospects for improvement can be seen in the health professional formation, cost-effectiveness report publication and the use of cost-effectiveness analysis. This study is an overview of the use of opinions provided by the HAS. This thesis established a basis to reflection on the use of economics reports and models in the hospital decisions.

[Evaluation of dental medical devices: Focus on the definition of needs]. / Évaluation des dispositifs médicaux dentaires pour un appel d'offres : privilégier la haute définition des besoins.

OBJECTIVES: As a university teaching hospital, the call for tender for dental medical devices (dental implants and consumables) is done with the help of a team of hospital pharmacists and users. In order to optimize the definition of needs and evaluation criteria, an exhaustive review of the products was carried out. METHODS: Dental medical devices suppliers were consulted in 2017 for reviewing their products. Their technical, clinical and economic data were compared. The products have been gathered into categories and its results had been submitted to a commission of dental experts of our university hospital for clinical opinion. RESULTS: More than 30,000 references from 30 different suppliers were analyzed (orthodontics, dental implants, membranes and bone substitutes, various dental consumables). Relating to oral implantology, the opinions converged on clinical studies. On the contrary, diverging opinions have been proffered on the systematic use of single-use drills and customized guides for surgery and on the implant's choice. The definition of needs has been specified for orthodontics and consumables. Other criteria played a great role: single packaging (unit doses), product's sterility, paediatric needs, presence of allergens, traceability of devices and supplier diversity. CONCLUSIONS: This review led to the identification of new needs in more precise terms. The complexity and diversity of dental products and techniques requires this careful review and a better collaboration with practitioners.

[Market access agreements: Definition and features. Could MAA be defined as a solution for immunotherapy funding by French health system?] / Les contrats d'accès au marché : définition et caractéristiques. Une solution pour garantir la prise en charge de l'immunothérapie par le système de santé français ?

Over the last few years, many therapeutic innovations have been approved and marketed in France, within a strained financial setting. Legal dispositions allowed manufacturers (LEEM - les enterprises du medicament) and the economic committee for health products (CEPS) to contract various confidential market access agreements to contain health product expenses. The purposes of this article are to define and describe these different existing market access agreements and to open discussion on their applicability to the problematic of immune-oncology drugs financing. Financial agreements, which led to major savings (discounts refunded to the public payer), have not responded completely to the therapeutic innovations financing problems. Performance agreements (funding based on real-life data and effectiveness of the drug) constitute a hope for health products financing, but major methodological challenges for their use in routine restrict them to rare cases only today. Even though several financial agreements could partly respond to this problematic, use of performance agreements could really constitute an interesting track to tackle this issue.

[Economic impact of etanercept and adalimumab biosimilars on hospitals scale covered by PharmAlp'Ain, a hospitals grouping of orders for health products]. / Évaluation de l'impact économique des biosimilaires d'étanercept et d'adalimumab à l'échelle des établissements adhérents au groupement de commandes PharmAlp'Ain.

OBJECTIVES: To evaluate the economic impact of future prescriptions of etanercept and adalimumab biosimilars at the territorial scale covered by PharmAlp'Ain, a hospitals grouping of orders for health products. METHODS: Determination of the number and status of patients (naive or in continuation of treatment) from the National Database "Datamart de Consommation Inter-Régimes" of health insurance, concerned by a dispensation in a pharmacy of etanercept or adalimumab in 2015. Calculation of potential savings in case of biosimilar requirements according to 3 hypotheses: 63% (rate observed in a previous study) of initiations are treated with biosimiliaries and the others by princeps (H1); all initiations under biosimilars and continuation therapy with the princeps (H2) or all patients are treated with biosimilars (H3). RESULTS: The annual savings are estimated at 237,000 € with the H1 hypothesis. In the case of H2, the expected savings would be 376,200 € per year. In the case of H3, savings for the community could reach almost 1,282,800 € per year. CONCLUSION: The arrival of biosimilars allows significant savings for medicines market. According to the French recommendations in 2016, the expected savings are between the H1 and H2 hypothesis. The rate of penetration of biosimilars depends on many factors such as the involvement of health professionals, patient adherence, or health authority recommendations.

[Cost of clotting factors in hospitalization]. / Coût des facteurs antihémophiliques en hospitalisation.

OBJECTIVES: Hemophilia is a rare genetic disease, characterized by uncontrolled bleeding. Injections of clotting factor are the principal are the principal treatment. This drug is very expensive. The objectives of this study are to determine the cost of clotting factor for in patients and the factor impacting this cost. METHODS: A retrospective study was carried on hemophiliac in patients between 1 January 2014 and 31 December 2015 in Cochin hospital and having received at least an injection of clotting factor during their hospitalization. A collection of clinical data and treatments received during the hospitalization was realized for every patient. RESULTS: Fifty-one patients were included in the study with a total of 68 hospitalizations. The median cost of clotting factors by hospitalization was 16,908€. The median part of clotting factors on the total cost of the hospitalization was 68.2%. The cost of factors by stay was higher for the severe haemophiliacs (P=0.015) and for the major surgeries (P<0.0001). The daily median cost of clotting factors was 3124€. This cost was higher at the haemophiliacs B (P=0.0112), the severe haemophiliacs (P<0.0001) and the haemophiliacs with inhibitor (P=0.0053). CONCLUSIONS: Clotting factors represent the most part of the cost of hospitalization of a haemophiliac. Their cost in hospitalization varies according to many factors. It may evolve with the arrival of long-acting clotting factors.

[Perspective of the transition from reusable instruments to single use ancillary in orthopedic surgery]. / Ancillaires orthopédiques : évolution du matériel restérilisable vers l'usage unique, quels impacts ?

OBJECTIVES: Since 2009, single-use (SU) ancillaries for total knee arthroplasty (TKA) and total hip arthroplasty (THA) have been marketed to replace reusable ancillaries. The concept is not innovative but their use in orthopedics is still uncommon. An assessment has been done for the use of SU ancillary in Assistance publique-hôpitaux de Paris with the consequences for the patient, the surgeon and the hospital. METHODS: A technical and a clinical review has been done with those devices in 2015. The economic and organizational impacts were identified and submitted for opinion to committee experts in orthopedics. RESULTS: Three SU ancillaries are commercialized. No clinical studies are currently available. There is no reimbursement for SU ancillaries whereas reusable ancillaries are included in prosthesis reimbursement price. Although SU ancillaries (TKA and THA) saving costs for sterilization, the annual additional budget estimated for their purchase would approximately be 2.5 times higher. Nevertheless, indirect savings could be also considered in the long-term period (global costs for sterilization, volume effect…). For the same quality, according to the experts, organizational impacts are low for the patient and the surgeon but potentially important for the hospital, the nursing and pharmaceutical staff, and logistical activities. CONCLUSIONS: On logistic, clinical and financial aspects, SU ancillaries need more evaluation. The switch to SU ancillaries allows saving sterilization costs and time, and provided an immediate mobilization of the equipment but their interest must be demonstrated by clinical and economic data.

[Review of patient-specific instrumentation for total knee prosthesis]. / Revue des guides personnalisés à usage unique dans les prothèses totales de genou.

OBJECTIVES: Single use patient-specific instruments (PSI) for total knee prosthesis are introduced as a new alternative to conventional ancillaries and computer assisted surgery by improving implants positioning. An exhaustive review was carried out to identify their specific characteristics, with their advantages and disadvantages. METHODS: Medical devices suppliers were consulted in 2015 for reviewing their PSI. Their technical, clinical and economic data were compared. The results had been submitted to an orthopaedics expert commission of our university hospital for clinical and financial opinion. RESULTS: Ten companies have provided the documentation for the analysis. PSI are manufactured by suppliers using a three dimensional printing method based on CT scans or MRI images. PSI are produced according to the surgeon's preferences after a preliminary data check, which can be performed by the suppliers' engineers, the surgeon and automatic calculation. Five suppliers can produce sterile PSI with optional delivery of 3D bone models. According to the experts, the studies failed to demonstrate the superiority of a PSI or hospital economic gain. The prices listed remain high and operating room time is not always significantly reduced. CONCLUSIONS: With the development of personalized medicine, the role of PSI grows in importance. They facilitate the surgeon's work by fully respecting the anatomy. These systems offer an interesting perspective in their technical and pedagogical aspects. But it seems premature to take them into routine use given the low number of high-level studies that were currently done.

[Impact of the expiry of the patent on quality and price of medicines at hospital: Study of five anticancer drugs from 2008 to 2015 at the Assistance publique-Hôpitaux de Paris]. / Impact de la chute des brevets sur le critère « qualité ¼ et sur le prix des médicaments à l'hôpital : étude sur cinq anticancéreux entre 2008 et 2015 à l'Assistance publique­Hôpitaux de Paris.

OBJECTIVES: Anticancer drugs were in 2005 the first expenditure item of the hospital drugs. Ten years later, it is noted that the placing on the market of generic drugs has led to a strong decrease of their price. To determine whether this decrease comes at the expense of product quality, a price-quality ratio trend study of five anticancer drugs was performed at AP-HP. METHOD: This work concerns docetaxel, oxaliplatin, gemcitabine, irinotecan and paclitaxel, and focus on the transition period between monopoly conditions and competitive situation (2008 to 2015). The price is set by calculating the cost per milligram of each specialty. Quality is evaluated by the average of quality marks obtained during the analysis of the tenders received in the purchasing procedures on four assessment criteria: ready for use form, stability of the solution after dilution, safety use and labeling. RESULTS: Between 2008 and 2015, the price per milligram of these anticancer drugs decreases, following the placing on the market of generic drugs. The quality of the tenders is maintained and even improved in many cases. On average, generic rating quality, lower than that of the originators in 2008, are now the highest. CONCLUSION: This study allows an objective basis of the effects of the drop in patent originator medicines. The placing on the market of generic drugs has a double positive result for the buyer: strong price cuts, parallel to the quality improvement, through the example of five anticancer drugs studied.

[Use of a Delphi survey to assess the hospital economic impact of innovative products: The example of idarucizumab a dabigatran-specific reversal agent]. / Utilisation du questionnaire Delphi pour anticiper l'impact économique des innovations thérapeutiques à l'hôpital : application à l'idarucizumab, le nouvel agent de réversion spécifique au dabigatran.

OBJECTIVES: The economic impact of therapeutic innovations on the hospital patient management cannot be easily estimated. The objective of this study is to illustrate the use of a Delphi survey as a support tool to identify the changes following the use of idarucizumab in dabigatran-treated patients with uncontrolled/life-threatening bleeding or who required emergency surgery/urgent procedures. METHODS: The Delphi questionnaires have been administrated to 8 emergency physicians or anesthetists from 6 different hospital centers. Following the answers, an economic valorization has been carried out on every parameter on which a consensus was reached (at least 4 answers showing an identical trend). A mean management cost for each etiology with and without the use of idarucizumab has thus been identified. RESULTS: For gastro-intestinal and other life-threatening bleedings (excepted intracranial bleedings), the total management cost of the hospital stay was respectively 6058 € (-35%) and 6219 € (-34%) following the use of the reversal agent. The hospital management cost for intracranial bleeding is slightly increasing to 9790 € (+3%). The cost of a stay for emergency surgery decreases to 6962€ (-2%). CONCLUSIONS: This study shows a positive economic impact following the use of the dabigatran-specific reversal agent for patients with uncontrolled/life-threatening bleeding excepted in the case of intracranial bleeding. Moreover, it points out that a Delphi survey is an easy way to predict the hospital economic impact of a therapeutic innovation when no other evaluation is possible.

Prices of Orphan Drugs in Four Western European Countries Before and After Market Exclusivity Expiry: A Cross-Country Comparison of List Prices and Purchase Prices.

BACKGROUND: Increasing pharmaceutical expenditure challenges the sustainability and accessibility of healthcare systems across Europe. Confidentiality restraints hinder assessment of actual prices of Orphan Medicinal Products (OMPs). Hence, we assessed the real prices of brand-name OMPs around market exclusivity expiry (MEE). OBJECTIVE: We aimed to explore developments in published list prices (LPs) and confidential hospital purchase prices (PPs) of brand-name OMPs relative to their market exclusivity status in Western European countries with similar GDPs. METHODS: We analyzed LPs and PPs of 13 selected OMPs purchased by university hospitals in Western European countries between 2000 and 2020. For confidentially reasons, proportions were used, with the Dutch LPs of the selected OMPs at the year of MEE serving as reference values. PPs included pre-purchase discounts. Rebates were not considered. RESULTS: Data were analyzed from hospitals in Denmark (DK) (n = 1), France (FR) (n = 1), Germany (DE) (n = 2), and the Netherlands (NL) (n = 1). Average LPs and PPs of included OMPs dropped gradually but limited over time, with no explicit price drop after MEE. LP levels differed more per country than PP levels: LP range before MEE was 164% (DE)-101% (FR) and after MEE was 135% (DE)-82% (FR); PP range before MEE was 150% (DE)-102% (FR) and after MEE was 107% (DE)-80% (FR). Overall differences between LPs and PPs were < 3% in all countries, except for Denmark. CONCLUSION: No evident price drops of included brand-name OMPs were observed around MEE and differences in purchase prices are modest in the selected Western European countries. Results were not subject to significance testing. More robust data are needed to strengthen negotiations with suppliers.

Melatonin in children with autistic spectrum disorders: recent and practical data.

Over the last 20 years, melatonin, a pineal hormone synthesized from serotonin, has been implicated in various studies on the autism spectrum disorder (ASD) and altered melatonin levels were detected in subgroups of subjects with ASD. Its effect on sleep disturbances got the attention of clinicians and several investigations were carried out to determine the usefulness and safety of melatonin administration in this disorder. Hypotheses were also raised regarding the possibility that the dysfunctional synthesis and secretion of melatonin detected in subgroups of subjects with ASD may increase the risk as well the severity of ASD. The purpose of this paper is to review our pharmacokinetic knowledge on melatonin and present results from recent studies on sleep disorders in autism, their treatment with melatonin and the impact of melatonin prescription in children with ASD evaluated in a Diagnostic Center for Autism Spectrum Disorder in Paris, France.

[Treatment of a serious autistic disorder in a child with Naltrexone in an oral suspension form]. / Traitement d'un enfant autiste par la naltrexone.

UNLABELLED: CLINICAL BACKGROUND: Autism is a developmental disorder that is usually diagnosed in early childhood. According to ICD-10 criteria, autism can be characterized by delays in language skills, by impaired social interaction, verbal or non-verbal communication and by repetitive, stereotyped or severely restricted activities and interests. The causes of autism are not yet elucidated, but both genetics and environment seem to play a role in 10 to 25% of autism cases. Several biochemical abnormalities, such as impairment of serotoninergic, catecholinergic, dopaminergic, and opioid systems have been reported. Autism therapies are designed to treat symptoms, and medication can be associated with psychoeducational and environmental interventions. Generally, the medications that are currently used are not intended for autism, and must be used with caution and selected according to the type and intensity of symptoms. The most common medication consists of psychotropic therapies by administration of dopaminergic and/or serotoninergic receptor antagonists (haloperidol, risperidone, clomipramine). Several drugs, such as anxiolytics (buspirone), mood stabilisers (lithium, sodium valproate), vitamins (vitamins B6, B12) or opioid antagonists (naltrexone) can be prescribed, in second intention, in cases of severe behavioural disorders. The prescription of opioid antagonists is based on the possible implication of an opioid system disorder observed in some cases. Nevertheless, several clinical studies reveal its variable effectiveness. Naltrexone is a competitive antagonist of opioid receptors OPRM1, OPRD1 and OPRK1. In France, this drug is prescribed for treating opioid and alcohol dependence. Moreover, several studies describe naltrexone as a possible treatment of autistic children in cases of developmental disorder and hyperactivity. CLINICAL CASE: In the Child and Adolescent Psychopathology Department of Sainte-Anne's Hospital, autistic children benefit from a multidisciplinary treatment program that sometimes includes the administration of psychotropic medication. One of these children presented with a severe autistic disorder according to the Childhood Autism Rating Scale (CARS). Considering ICD-10 criteria, he benefited from a multidisciplinary program, associating cognitive psychotherapy, psychomotor rehabilitation, speech therapy and educational intervention. However, persistent sleep disorder and motor instability led to successive prescriptions of several different psychotropic drugs. Initial treatment by thioridazine (10mg per day) followed by propericiazine (2.5mg per day) improved sleep, but was not efficient in reducing self-mutilating behaviour. A new treatment by risperidone (from 0.5mg to 1.5mg per day) was therefore chosen; however it lost its efficacy after five months. Finally, an anxiolytic (cyamemazine) and a thymoregulator (sodium valproate) were successively tried without yielding any clinical improvement. Owing to the persistence of communication difficulties, major instability, self-mutilating behaviour and heteroaggressiveness, treatment with naltrexone was subsequently chosen with parental consent. In France, naltrexone hydrochloride is only available in tablet form (Nalorex 50mg and Revia 50mg), which is not adapted to children at the efficient dose. Consequently, an oral suspension form marketed in Spain (Antaxone 50mg) was imported, having obtained the Afssaps' (the French drug administration) authorisation for its temporary use. The Connors and Nisonger scales were used as outcome measures of behavioural symptom change. The Conners scale is used to assess attention deficit and hyperactivity, whereas the Nisonger scale analyses social skills and behaviour disorders in children and adolescents with mental retardation. The onset of treatment, at a dose of 1mg/kg/day, led to a transitory increase in negative behaviour. However, a dose of 0.75mg/kg per day subsequently led to significant improvements, as shown by outcome measurements. Self-mutilating behaviour disappeared completely. Certain side effects were observed, namely transitory sedation at the beginning of treatment and moderate constipation. CONCLUSION: This clinical case confirms that treatment of a serious autistic disorder in children using Naltrexone in oral suspension form is a potentially interesting therapeutic alternative for treating behavioural symptoms resistant to classical drug therapy.