"The drugs available in early 2018 for Alzheimer's disease have only minimal and transient efficacy. They are also difficult to use because of their disproportionate adverse effects and many interactions with other drugs. None of the available drugs has been shown to slow progression toward dependence, yet all carry a risk of life-threatening adverse effects and severe drug interactions. It is better to focus on reorganising the patient's daily life, keeping him or her active, and providing support and help for caregivers and family members." This statement has featured since 2014 in Prescrire's annual review of drugs to avoid, hundreds of thousands of copies of which have been downloaded from our website english.prescrire.org (1).

In May 2018, France's Minister for Health took this negative harm-benefit balance into account. She decided that, from 1 August 2018, these drugs – donepezil, galantamine, rivastigmine and memantine – would be delisted, i.e. no longer reimbursed by the national health insurance system (2,3). This measure was not unexpected. In late 2016, the French Pharmacoeconomic (Transparency) Committee had concluded that these drugs provide insufficient clinical benefit, and consequently asked for them to be delisted (4,5).

Increasingly disturbing data over time. The first drugs authorised for Alzheimer's disease in the mid-1990s brought genuine hope. But, in 1998, after analysing evaluation data, Prescrire concluded that their efficacy was only modest and purely symptomatic; nevertheless, from the data available at the time, their adverse effect profile appeared acceptable (4).

Over time, more data emerged on their serious and sometimes fatal adverse effects, while data concerning their efficacy against symptoms, dependence and disease progression proved more disappointing than expected. On top of which, they interact with many other drugs (4). In 2012, based on the evidence amassed by this point, Prescrire concluded that these drugs are more dangerous than helpful and advised health professionals against their use in order to protect their patients (6).

Wrongly pushed for years in France's national practice guidelines. In 2008, France's National Authority for Health (HAS) published its first clinical practice guideline on the management of Alzheimer's disease. It placed undue emphasis on drugs. Prescrire advised health professionals to ignore this HAS guideline (7). And Formindep, a non-profit organisation that promotes independence from industry influence in the field of healthcare, complained to the Conseil d'État (France's highest administrative jurisdiction) about this guideline, requesting its withdrawal on the grounds that the conflicts of interest of its contributors had not been taken into account. Without waiting for the ruling, the HAS withdrew its guideline in 2011 (8). But its next version still made no mention of the meagre efficacy of these drugs or their very many and very frequent adverse effects (9).

It was only in 2016, after a review of their harm-benefit balance by France's Pharmacoeconomic Committee, that the HAS finally acknowledged that these drugs have no place in the management of Alzheimer's disease and requested they be delisted (4,5). And in May 2018, the HAS published a new guideline affirming that these drugs have nothing to offer (10).

In practice. Alzheimer's disease is an ordeal for patients as they lose their faculties, and also for the family and carers on whom the patient becomes increasingly dependent. None of the drugs available in 2018 offer any lasting improvement. These delisted drugs even hasten death in some cases. It is only right that they should be delisted. The next logical step would be to withdraw them from the market in France and across Europe.

The delisting of these drugs is a clear signal that the days are over when support for patients and their struggling caregivers was based on drugs raising false hopes. These patients and their caregivers primarily need hands-on, practical care and support, not these drugs: practical help with daily tasks, stimulating activities for patients, psychological support for caregivers, temporary or lasting respite for family members. The least society can do now is to use the money previously wasted on reimbursing these drugs to fund initiatives of this type.

©Prescrire 15 June 2018

References:
1- Prescrire Editorial Staff "Towards better patient care: drugs to avoid in 2014" Prescrire Int 2014; 23 (150): 161-165 + "Towards better patient care: drugs to avoid in 2018" Prescrire Int 2018; 27 (192): 107-109.
2- APM "Les médicaments anti-Alzheimer bientôt déremboursés" 28 May 2018: 1 page.
3- "Arrêté du 29 mai 2018 portant radiation de spécialités pharmaceutiques de la liste mentionnée au premier alinéa de l'article L. 162-17 du code de la sécurité sociale" + "Arrêté du 29 mai 2018 portant radiation de spécialités pharmaceutiques de la liste des médicaments agréés à l'usage des collectivités publiques prévue à l'article L. 5123-2 du code de la santé publique" Journal Officiel, 1 June 2018: 16 pages.
4- Prescrire Rédaction "Médicaments de la maladie d'Alzheimer" Rev Prescrire 2016; 36 (398): 904.
5- HAS - Commission de la Transparence "Avis-Aricept + Ebixa + Exelon" 19 October 2016 + "Avis-Reminyl" 6 July 2016: 17 pages.
6- Prescrire Editorial Staff "Drugs for Alzheimer's disease: best avoided. No therapeutic advantage" Prescrire Int 2012; 21 (128): 150.
7- Prescrire Editorial Staff "Alzheimer's disease and other dementias: French guidelines are biased" Prescrire Int 2009; 18 (102): 185.
8- Prescrire Rédaction "Guides de pratique clinique de la Haute autorité de santé: trop de conflits d'intérêts cachés" Rev Prescrire 2009; 29 (309): 546.
9- Prescrire Rédaction "Guide "Maladie d'Alzheimer": gare aux malfaçons (suite)" Rev Prescrire 2012; 32 (343): 387.
10- HAS "Guide parcours de soins des patients présentant un trouble neurocognitif associé à la maladie d'Alzheimer ou à une maladie apparentée" May 2018: 37 pages.

Source: "Médicaments de la maladie d'Alzheimer: enfin non remboursables en France!" Rev Prescrire 2018: 38 (416).

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