RINVOQ (upadacitinib hémihydraté) - dermatite atopique

Key points

In adults

Favourable opinion for reimbursement in the treatment of moderate to severe atopic dermatitis in adults who are candidates for systemic therapy in the event of failure, intolerance or contraindication to ciclosporin.

Unfavourable opinion for reimbursement in the treatment of moderate to severe atopic dermatitis in adults in whom topical therapies have failed and who are ciclosporin-naïve, in the absence of comparative data.

In adolescents 12 years and older

Favourable opinion for reimbursement in the treatment of moderate to severe atopic dermatitis in adolescents 12 years and older who are candidates for systemic therapy.

What therapeutic improvement?

In adults

Therapeutic improvement compared to DUPIXENT (dupilumab) in the treatment of moderate to severe atopic dermatitis in adults who are candidates for systemic therapy, in the event of failure, intolerance or contraindication to ciclosporin.

In adolescents 12 years and older

No clinical added value in the treatment of moderate to severe atopic dermatitis in adolescents 12 years and older who are candidates for systemic therapy, which includes DUPIXENT (dupilumab).

Role in the care pathway?

The overall objective of atopic dermatitis (AD) treatment is to improve patients’ quality of life by treating their skin lesions and preventing the risk of secondary infections in the event of flare-ups, early relapses and xeroderma. Outside inflammatory flare-ups, all patients should be treated using adjuvant measures (hygiene, emollients) and relapses should be treated at an early stage.

Management in adults

The treatment of acute flare-ups is initially based on the use of topical treatments: topical corticosteroids or, in the event of failure/contraindication, a calcineurin inhibitor (tacrolimus). The wet wrapping technique may be used in the event of an inadequate response.

Phototherapy is mainly recommended in the management of the chronic phase but can be used as second-line treatment in acute flare-ups in the event of failure of topical treatments, although its use is limited by its accessibility.

Systemic treatments are reserved for severe chronic atopic dermatitis resistant to topical corticosteroids or phototherapy. The choice of systemic treatment depends on various factors, in particular comorbidities, age, clinical experience or potential pregnancy plans.

Non-biologic systemic treatments are currently available, including ciclosporin used as first-line treatment and immunosuppressive therapies used off-label (methotrexate, mycophenolate mofetil and azathioprine). Their use should be time-limited due to the unfavourable long-term safety profile.

Other treatment options have also become available recently: biologic interleukin inhibitors, an anti-IL4 and anti-IL13, dupilumab (2017) and an anti-IL-13, tralokinumab (June 2021) administered subcutaneously, and a janus kinase inhibitor (anti-JAK 1 and 2) administered orally, baricitinib (2020). These treatments are recommended by the Transparency Committee in the event of failure, intolerance or contraindication to ciclosporin.

Alitretinoin, a systemic retinoid, has an MA exclusively for the treatment of severe chronic eczema of the hands, following the failure of potent topical corticosteroids.

Management in adolescents aged 12 years and older

According to French and international guidelines, the treatment of acute flare-ups of atopic dermatitis (AD) in children and adolescents is initially based on the use of topical corticosteroids, as in adults, potentially with use of the wet wrapping technique if necessary. Topical tacrolimus has an MA in the treatment of severe atopic dermatitis in children and adolescents in the event of failure or contraindication to topical corticosteroids. However, the Transparency Committee considered that its clinical benefit in this age group was insufficient and it is only reimbursed in adults in France.

The use of phototherapy in the paediatric population is very marginal given the little data available in these patients, the administration conditions requiring several visits per week to a dermatologist with the required equipment, and the serious cumulative toxicity (mutagenic/carcinogenic risk, in particular).

In the event of an inadequate response to these treatments, ciclosporin is proposed in adolescents; however, its MA indicates that its use is not recommended in patients under the age of 16 years. In refractory atopic dermatitis in adolescents, other systemic immunosuppressants, such as methotrexate, azathioprine and mycophenolate mofetil, are proposed off-label. Their use should be time-limited due to an unfavourable long-term safety profile.

Since 2019, dupilumab has been an option in adolescents with moderate to severe atopic dermatitis who are candidates for systemic therapy (MA of 01/08/2019) and is reimbursable in this indication (Transparency Committee opinion of 11/03/2020).

Role of the medicinal product in the care pathway

In adults

As knowledge currently stands, in the absence of a direct comparison of upadacitinib (JAK1 and JAK1/3 inhibitor) with oral ciclosporin following the failure of topical treatments, its role compared to ciclosporin cannot be determined in first-line systemic therapy (following the failure of topical corticosteroids).

Consequently, RINVOQ 15 mg and 30 mg (upadacitinib) is a second-line systemic treatment to be reserved for adults with moderate to severe atopic dermatitis, who are candidates for systemic therapy, in the event of failure, intolerance or contraindication to ciclosporin.

The Transparency Committee specifies that the choice of second-line systemic therapy should be made on a case-by-case basis depending on the severity of the disease, patients’ characteristics, their treatment history, the risks of intolerance and contraindications to the various treatments available.

As regards upadacitinib, it is necessary to take into account its less favourable safety profile than that of dupilumab (see the respective SPCs of these medicinal products), the need to monitor various laboratory parameters (haematological, lipid and hepatic), its contraindication in the event of pregnancy, as with other JAK inhibitors, as well as uncertainties, in particular relative to the cardiovascular, venous thromboembolic and carcinogenic risks indicated in the RMP for upadacitinib and shared by other JAK inhibitors.

The superiority of upadacitinib compared to dupilumab was only demonstrated at the 30 mg dose, which the SPC indicates is reserved for patients with high disease burden or with an inadequate response to the 15 mg dose. 

In adolescents 12 years and older

Given the toxicity of ciclosporin, contraindicated in patients under the age of 16 years, the Committee considers that RINVOQ 15 mg (upadacitinib) is a first-line systemic treatment to be reserved for moderate to severe forms of atopic dermatitis in adolescents in whom topical treatment has failed.

As in adults, the choice of first-line systemic therapy should take into account the severity of the disease, patients’ characteristics, their treatment history, the risks of intolerance and contraindications to the various treatments available.

As regards upadacitinib, it is necessary to take into account its less favourable safety profile than that of dupilumab (see the respective SPCs of these medicinal products), the need to monitor various laboratory parameters (haematological, lipid and hepatic), its contraindication in the event of pregnancy, as with other JAK inhibitors, as well as uncertainties, in particular relative to the cardiovascular, venous thromboembolic and carcinogenic risks indicated in the RMP for upadacitinib and shared by other JAK inhibitors.

Special recommendation

The Committee wishes to highlight the fact that upadacitinib is contraindicated during pregnancy, due to the teratogenic effects demonstrated in animals, and that for women of childbearing potential effective contraception should be used during treatment and for 4 weeks following the final dose of upadacitinib (see the SPC for more details).