LECIGIMON (lévodopa/ carbidopa/ entacapone) - maladie de Parkinson à un stade avancé

Key points

Unfavourable opinion for reimbursement in the treatment of advanced Parkinson's disease with severe motor fluctuations and hyperkinesia or dyskinesia when available oral combinations of Parkinson medicinal products have not given satisfactory results.

Role in the care pathway?

The initial treatment strategy for the disease depends on the presence or otherwise of Parkinson's symptoms with functional impairment, with treatment only initiated in the presence of impairment. In cases of very mild impairment, treatments will be considered based on the predominant symptom and age, from monoamine oxidase B inhibitors (MAO-B inhibitors), dopamine agonists by the oral or transdermal route and anticholinergic agents.

In the event of functional effects, dopamine agonists will be preferred for patients under 65 years of age whereas L-Dopa will be preferred for elderly subjects.

After a stabilisation period of varying duration, the clinical status deteriorates due to the onset of motor complications associated with the dopaminergic treatment (motor fluctuations, on/off effects, dyskinesia) and the onset or deterioration of non-dopa-dependent symptoms specific to the disease. A review of the medical prescription and of the associated medicines liable to impair motor and non-motor complications should be conducted, optimising the dopa therapy thereafter if necessary to target continuous dopamine stimulation (division of the daily dose, adaptation of dosing times, change of pharmaceutical form, dietary changes).

The addition of L-dopa treatment can be envisaged subsequently, with:

As first-line treatment:

* dopamine agonists administered per os or transdermally: 

• non-rye ergot-derived agents as first-line treatments: ropinirole, piribedil, pramipexole, rotigotine (transdermal device).
• rye ergot-derived agonists, which require annual cardiac monitoring by ECG (risk of the development of valve disease): bromocriptine, lisuride;

* COMT inhibitors, with:

• entacapone, which has the benefit of significantly increasing the duration of ON episodes and can often make it possible to reduce L-dopa doses;
• tolcapone, if entacapone is not sufficiently effective or is poorly tolerated (treatment with tolcapone must not exceed 3 weeks in the event of inefficacy due to its toxicity, particularly hepatic, and regular assay of AST-ALT is necessary)

* MAO-B inhibitors.

A combination of these different substances may also be envisaged.

As second-line treatment:

• anticholinergic antitremor agents, only in patients with no cognitive impairment,
• amantadine remains a useful treatment option in the management of levodopa-induced dyskinesia or fluctuations. In other clinical situations in Parkinson’s disease, particularly at the start of the disease, immediate-release amantadine has no role in the care pathway in view of the medicinal alternatives.
• discontinuous subcutaneous apomorphine injections indicated as an adjuvant treatment for severe dopa therapy activity fluctuations in the course of Parkinson's disease (on-off effects).

As a last resort, and in accordance with national, European (EFNS/MDS-ES) and international guidelines, invasive treatments such as deep brain stimulation, continuous subcutaneous apomorphine infusion or enteral levodopa-carbidopa administration may be envisaged for some patients.

Role of LECIGIMON (levodopa/carbidopa/entacapone) in the care pathway:

Considering:

• limited data from a pharmacokinetic study versus DUODOPA (levodopa/carbidopa) conducted in the short term (two days) on a small number of patients (n=11), not having demonstrated the clinical value of adding entacapone to levodopa/carbidopa dual therapy administered via an implantable pump;
• the fact that the implantable pump administering LECIGIMON (levodopa/carbidopa/entacapone) is different from that administering DUODOPA (levodopa/carbidopa), making it necessary to change the pump following any change of treatment,

the Committee considers that LECIGIMON (levodopa/carbidopa/entacapone) has no role in the treatment strategy for adult patients with advanced Parkinson’s disease.