To get out of the controversy surrounding the use of Baclofen, and to decide on a possible marketing authorization, the drug agency (ANSM) has set up a special and transparent procedure. Comments from Professor Jean-François Bergmann, Head of the Department of Internal Medicine at the Lariboisière Hospital, in Paris and Professor of Therapeutics at the University of Paris Diderot is also former vice-president of the Marketing Authorization Commission (Marketing Authorization) for Medicines.
Baclofen is a muscle relaxant of central action which has been approved for nearly 40 years for the treatment of muscle spasticity. For about ten years, the virtues of helping alcohol withdrawal and maintaining abstinence have been attached to it and widespread use outside of Marketing Authorization has been observed in France in an atmosphere that is at least passionate.
Stone Age
It all started in 2008 with a book by Doctor Olivier AMEISEN: “The Last Glass” in which he told the end of his alcoholic addiction and the maintenance of his withdrawal thanks to high doses of Baclofen. Very quickly, this treatment was used off-label to obtain or maintain abstinence in alcoholics.
Tens of thousands of patients have been treated on a notion of efficacy transmitted by word of mouth. Given the extent of this use, the National Medicines Safety Agency (ANSM) has set up a temporary recommendation for use (RTU) which has enabled more than 120,000 patients to benefit from this treatment. Very quickly the controversy swelled in front of the very wide use of a drug not devoid of undesirable effects.
The pro-Baclofen (“Probaclo”) have underlined the seriousness of alcoholism in France with a mortality amounting to tens of thousands of patients each year, the urgency of the provision of a drug appearing effective and the impression of obvious benefit built on numerous testimonials and individual experiences. A militant front has formed demanding the right to access this drug pending more formal proof of effectiveness.
Opposite the anti-Baclofen (“Antibaclo”) considered that this drug, like all the others, should only be used after a marketing authorization proving a favorable benefit / risk ratio. They considered that obtaining clinical evidence should precede large-scale use and their reservation was based on a number of data indicating a lower efficacy than that advanced by Probaclo associated with risks of adverse effects. sometimes serious or even fatal associated with the use of this centrally acting medication.
The age of Reason
In recent years, we have finally obtained scientifically valid elements to better understand the effectiveness and risks associated with this treatment. About fifteen controlled, randomized, double-blind trials, of variable methodological quality, are gradually becoming available, as are three meta-analyzes.
The Société Française d’Alcoologie recently carried out an exhaustive analysis of this literature by separating trials evaluating withdrawal doses from trials evaluating aid to abstinence. For them, most of the controlled trials are negative and they conclude that the current scientific data are insufficient to have a real appreciation of the benefit / risk ratio of Baclofen. They argue for new controlled studies conducted more rigorously than previous ones.
At the same time, a certain amount of epidemiological data, mainly French, was obtained from the 120,000 patients treated. Despite the methodological fragility of these retrospective cohorts, they attempted to assess the efficacy and above all the risk of Baclofen, which appears to be dose-dependent, which led the ANSM to recommend dosages below 80 mg / day.
But above all, a French pharmaceutical laboratory, owner of the two main randomized studies recently carried out (Alpadir and Bacloville) has submitted a request for a national MA to the ANSM. This national MA procedure is in disuse since most of the developments are made at world level and MA applications are almost exclusively European. However in the present case, with a molecule previously having a French Marketing Authorization in muscle spasticity, with an almost exclusively hexagonal use and with mainly French clinical trials, it was logical to start with a request for a national Marketing Authorization.
The Medicines Agency therefore has an important and delicate decision to make. To do so, to protect itself from possible criticism of both Probaclo and Antibaclo, it has surrounded itself with numerous collaborations and has called on a relatively new procedure: on the one hand, a temporary specialized scientific committee has been created in charge of ” analyze all the scientific data on Baclofen, on the other hand the MA decision will be taken jointly by three committees existing at the ANSM, the committee for the initial assessment of the benefit and the risk (since is a new Marketing Authorization), the commission for monitoring the ratio between the benefit and the risk of drugs (since Baclofen has already been on the market for almost 40 years) and the commission for psychotropic drugs and narcotics (since this drug has a central action). These three committees will decide before the summer. The debates will be public and broadcast on the Internet.
We can congratulate ourselves on the transparency efforts implemented in this unprecedented scientific situation. But the final decision will be heavy with meaning and it is therefore necessary that it be taken as rigorously as possible and in complete independence.
Towards the golden age?
It is unfortunately illusory to think that a single molecule alone can solve the difficult multifactorial problem of alcoholism. But conversely, given the few therapeutic options that currently exist, any new effective strategy is welcome.
Either the ANSM ad hoc committees consider that the benefit / risk ratio of this drug is favorable, they will then have to give the Marketing Authorization, specify the target population and the dosage. It is certain that marketing will have to be surrounded by surveillance measures, a risk management plan, epidemiological data, monitoring of patients treated. If the benefit / risk ratio of the drug is unfavorable, this must be clearly stated, not to give Marketing Authorization and to stop RTU so that the use of a drug that is more harmful than beneficial will gradually cease. Finally, it is possible that the exhaustive analysis of data from science, clinical trials and pharmacovigilance data will not allow a formal decision to be taken in the absence of strong and convincing scientific evidence. It will then be necessary to conduct new, rigorously conducted clinical trials.
Despite the urgency and gravity of the pathology, it is preferable to give yourself a few more years to have solid scientific data rather than to make a drug that is not well known and which is difficult to obtain in a free and uncontrolled manner. ‘assess calmly.
It is as dangerous to deprive patients of an effective drug as it is to allow a potentially dangerous drug to be used. The rigor and the seriousness of the evaluation put in place by the ANSM to decide on the MA for Baclofen must be emphasized. Let us hope that his final decision will be respected by all.
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