ILARIS - Maladie de Still (canakinumab)

Key points

Favourable opinion for reimbursement in the treatment of adult-onset Still's disease (AOSD) in patients who have responded inadequately to previous therapy with non-steroidal anti-inflammatory drugs (NSAIDs) and systemic corticosteroids.

What therapeutic improvement?

No clinical added value in the therapeutic strategy.

Role in the care pathway?

A French national diagnostic and care protocol (PNDS) was produced by reference centres for adult-onset Still's disease (AOSD) in 2018. According to this protocol, the treatment of AOSD has several objectives: “control of the symptoms of AOSD and achievement of clinical and laboratory remission (absence of signs of the disease), the prevention of erosive joint involvement, the prevention of systemic complications of chronic inflammation and of treatment-associated adverse effects”.

Symptomatic treatments include analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroid infiltrations and non-medicinal treatments (putting ice on the joints, relaxation, sophrology or hypnosis for chronic pain).

As regards DMARDs, only two IL1 inhibitors - anakinra and canakinumab - have an MA in this indication. Despite the absence of an MA, several treatments are proposed off-label according to the PNDS, in particular methotrexate, tocilizumab (IL6 inhibitor) or TNF inhibitors.

According to the care pathway established by the PNDS, in the event of failure or a partial response to NSAIDs and systemic corticosteroids, the second-line treatment should be discussed at a multidisciplinary team (MDT) meeting. The guidelines recommend the use of biologic therapy with an IL1 inhibitor (anakinra or canakinumab) or even an IL6 inhibitor (tocilizumab) due to their superior efficacy to methotrexate. Methotrexate nonetheless retains a role in forms predominantly affecting the joints or with few symptoms. Targeting the inflammasome pathway, and hence the IL1 pathway appears to be more specific to AOSD, in fact, and should therefore be favoured. It should be noted that these biologic therapies can be used as monotherapy or in combination with methotrexate.

In the event of resistance to second-line treatment, a switch to the other IL1 inhibitor is proposed, and in the event of primary failure, tocilizumab should be introduced directly.

Finally, in the event of failure or a partial response to this third-line treatment, the initiation of a TNF inhibitor may be proposed at an MDT meeting, although the efficacy and, especially, the therapeutic maintenance rate of the latter are inferior to those of IL1 and IL6 inhibitors.

The safety of ciclosporin limits its value but it may nonetheless be useful in some complex or refractory situations.

In all cases, in the event of prolonged remission (> 6 months), a reduction in DMARDs may be attempted, either by reducing the doses (methotrexate or IV biologic therapy), or by increasing the interval between injections (subcutaneous biologic therapies).

Role of the medicinal product in the care pathway

In the treatment of adult-onset Still's disease (AOSD), ILARIS (canakinumab) is a second-line treatment, in the same way as KINERET (anakinra), to be used in patients who have responded inadequately to previous therapy with NSAIDs and systemic corticosteroids, considering:

• its efficacy established in paediatric patients with systemic juvenile idiopathic arthritis (SJIA) and the clinical continuum with AOSD, and
• the well-established use of ILARIS (canakinumab) in patients with AOSD, supported by expert recommendations and numerous observational data available in the literature.

Considering the specificities of the disease in terms of its rarity and seriousness, as well as the low level of evidence of the available data, the Committee recommends that the decision to prescribe ILARIS (canakinumab) should be taken at a multidisciplinary team meeting in reference and expert centres belonging to the rare auto-immune and auto-inflammatory diseases network (FAI²R).

The Committee recommends that ILARIS (canakinumab) be used in accordance with the strategy established in the context of the PNDS, particularly in terms of the recommended dose (150 mg / month SC).

Special recommendations

The Committee recommends:

• that the decision to prescribe ILARIS (canakinumab) be taken at a multidisciplinary team (MDT) meeting in reference and expert centres belonging to the FAI²R network given the specificities of the disease and low level of evidence of the available data,
• that ILARIS (canakinumab) be used in accordance with the strategy established in the context of the PNDS, particularly in terms of the recommended dose (150 mg / month SC), and
• that the first subcutaneous injection of this medicinal product be administered in an appropriate healthcare setting given the rare but serious risk of systemic reactions to the injection, including anaphylactic reactions with canakinumab (as well as with other biologic DMARDs).