RINVOQ (upadacitinib) - Rhumatisme psoriasique

Key points

Favourable opinion for reimbursement in the treatment of active psoriatic arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs (DMARDs). RINVOQ (upadacitinib) may be used as monotherapy or in combination with methotrexate.

What therapeutic improvement?

No clinical added value in the therapeutic strategy.

Role in the care pathway?

The objectives of treatment are to control symptoms (inflammation, pain and spinal stiffness) and prevent structural damage in order to preserve or improve the functional capacities, autonomy, social participation and quality of life of patients and obtain clinical remission or, failing this, a low level of disease activity.

Nonsteroidal anti-inflammatories (NSAIDs) (up to the maximum authorised dose) are the reference first-line treatment. Analgesics can be used for residual pain, in conjunction with the other therapies. Local corticosteroid injections may be considered for arthritis and enthesitis.

As first-line therapy, conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) (methotrexate, leflunomide, sulfasalazine) should be considered in the event of peripheral arthritis refractory to symptomatic treatment. They have not demonstrated efficacy on isolated axial or enthesitic manifestations.

As second-line therapy, in the event of inadequate response, contraindication or intolerance to conventional disease-modifying anti-rheumatic drugs, biologic disease-modifying anti-rheumatic drugs (bDMARDs) or targeted synthetic therapies (tsDMARDs) may be considered.

The biologic therapies currently available include TNF inhibitors (adalimumab, etanercept, infliximab and certolizumab pegol) and interleukin inhibitors (an IL12/23 inhibitor, ustekinumab, two IL17 inhibitors, secukinumab and ixekizumab, and, recently, an IL23 inhibitor, guselkumab). TNF inhibitors and interleukin inhibitors have identical MAs from the second line of treatment, but the Committee recommends that interleukin inhibitors be used preferentially in the event of failure of TNF inhibitors (i.e., as third and later-line treatment).

In addition, another JAK inhibitor (tsDMARD), tofacitinib (XELJANZ), also has an MA in the event of failure of at least one conventional DMARD (i.e., from the second line). Given the absence of clinical studies having directly compared tofacitinib with TNFα antagonists, the latter should be favoured as second-line disease-modifying therapy. In the absence of data versus interleukin inhibitors, the role of JAK inhibitors cannot be specified compared to these medicinal products.

In patients with non-severe, not very active forms, having responded inadequately to at least one csDMARD and in whom neither bDMARDs nor JAK inhibitors are appropriate, apremilast (OTEZLA), a PDE4 inhibitor, may be considered.

Role of RINVOQ (upadacitinib) in the care pathway:

Given the absence of demonstrated superiority of upadacitinib 15 mg compared to adalimumab (TNF inhibitor) and the greater experience in terms of efficacy and safety with this family of drugs, the Committee considers that in the event of failure of a conventional disease-modifying drug (i.e., in second-line therapy), TNF inhibitors should be favoured first. RINVOQ (upadacitinib) primarily has a role following the failure of at least one TNF inhibitor (i.e., as third and later-line therapy).

In the absence of direct comparison between upadacitinib and the other treatment options available following the failure of at least one TNF inhibitor, (interleukin inhibitors and JAK inhibitors), its role compared to these medicinal products cannot be specified.

Special recommendations

The Committee highlights that it is important to manage cardiovascular risk factors given the increased cardiovascular risk in chronic inflammatory arthritis.