KINERET - Fievre mediterraneenne familiale (FMF)

Key points

Favourable opinion for reimbursement in the treatment of Familial Mediterranean Fever (FMF) only when colchicine is ineffective, poorly tolerated or contraindicated.

What therapeutic improvement?

No clinical added value in the therapeutic strategy.

Role in the care pathway?

According to the treatment guidelines, in the absence of curative treatment, management is based on symptomatic treatment of disease flares and their prevention, the aim being to prevent complications, particularly related to amyloidosis, and preserve patients’ quality of life.

The treatment of Familial Mediterranean Fever (FMF) is based exclusively on symptomatic treatment. Inflammatory flares require rest and justify time off work or school throughout the duration of symptoms. Treatment of inflammatory flares involves analgesics, antipyretics, nonsteroidal anti-inflammatory drugs (NSAIDs), and corticosteroid therapy for as short a time as possible.

Concerning maintenance therapies, apart from anakinra (anti-IL1) another two proprietary medicinal products currently have an MA in FMF: colchicine and canakinumab (ILARIS, anti-IL1).

According to the French national diagnostic and care protocol (PNDS) produced in 2013 as well as the 2016 European Alliance of Associations for Rheumatology (EULAR) guidelines, colchicine is effective in the prevention of flares and amyloidosis. It is recommended as first-line treatment and should be taken daily for life. However, its use is contraindicated in the event of severe renal or hepatic impairment.

In the rare patients (3 to 5%) not responding or resistant to colchicine, biologic therapies, and in particular anti-IL1 inhibitors (canakinumab and anakinra) should be envisaged. These should be given in combination with colchicine wherever possible in order to reduce the risk of amyloidosis (except in the event of intolerance or contraindication to this drug). In the absence of comparative data, anakinra and canakinumab are options that can be used at the same stage in the strategy.

According to the PNDS, the effects of the other treatments proposed in the literature are controversial and they cannot be recommended (corticosteroids, interferon alpha, thalidomide, TNF alpha inhibitors, etc.).

Role of the medicinal product in the care pathway

KINERET (anakinra) is a second-line treatment, in the same way as ILARIS (canakinumab), to be reserved for patients with Familial Mediterranean Fever (FMF) only when colchicine is ineffective, poorly tolerated or contraindicated, considering:

• well-established use in clinical practice in these patients and recognition of this use by the national and European guidelines and by experts,
• and its documented efficacy in the literature despite the low level of evidence of the available data, the clinical study conducted by Ben-Zvi et al. in 2017 and numerous observational studies.

In accordance with the Ben-Zvi et al. 2017 study and the SPC, the Committee recommends that anakinra (KINERET) be used in combination with colchicine wherever possible, since this is the only treatment to have demonstrated efficacy against the development of amyloidosis.

The attention of physicians is drawn to the fact that, in patients demonstrating no clinical improvement, the benefit of continued treatment with KINERET (anakinra) should be reassessed.

Special recommendations

The Committee recommends:

• that the decision to initiate treatment with KINERET (anakinra) be taken after a documented proposal resulting from a treatment review meeting with a reference centre with expertise in the treatment of FMF, and
• that the first subcutaneous injection of this medicinal product be administered in an appropriate healthcare setting given the rare but serious identified risk of systemic reactions to the injection, including anaphylactic reactions with anakinra (as well as with other biologic DMARDs).