RINVOQ (upadacitinib)

Key points

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

What therapeutic improvement?

No clinical added value in the therapeutic strategy.

Role in the care pathway?

According to French and European guidelines, the treatment of rheumatoid arthritis (RA) is based on the early prescription of a disease-modifying anti-rheumatic drug (DMARD) in order to induce clinical and laboratory remission. Pending the efficacy of a DMARD, corticosteroid therapy may be proposed, which will be reduced and stopped as soon as possible. Close monitoring and frequent treatment adjustments are necessary until the objective is attained.

In first-line treatment, methotrexate (MTX) is the reference conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) for rheumatoid arthritis. In the event of a contraindication or intolerance to MTX, leflunomide or sulfasalazine can be used. The Committee considers that the prescription of a biologic therapy (in combination or as monotherapy) is not justified as first-line treatment, unless all csDMARDs are contraindicated.

In second or later-line therapy, in patients who have responded inadequately or who are intolerant to MTX, treatment should be optimised as follows:

• In the absence of factors for a poor prognosis, a combination of synthetic disease-modifying anti-rheumatic drugs (MTX/sulfasalazine/hydroxycholoroquine) or a rotation for another synthetic disease-modifying anti-rheumatic drug (leflunomide, sulfasalazine) may be proposed. In the event of failure (or contraindication), targeted therapy should be considered. Possible targeted therapies in this situation are: targeted biologic therapies (biologics or bDMARDs) represented by TNF inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), interleukin 6 receptor antagonists (tocilizumab and sarilumab), T lymphocyte co-stimulation modulator (abatacept), or rituximab in certain circumstances only, as well as synthetic targeted therapies (tsDMARDs) represented by JAK inhibitors (baricitinib and tofacitinib), although the Committee recommends their use following the failure of a biologic (third or later line),
• In the presence of factors for a poor prognosis, the addition of a targeted therapy to MTX may be proposed.

It should be noted that the use of targeted therapy should be preferentially implemented in combination with MTX. However, if it is necessary to use targeted therapy as monotherapy, an IL6 inhibitor or a JAK inhibitor should be favoured given their demonstrated superiority as monotherapy compared to MTX alone.

It is not possible to establish a preferential hierarchy within the targeted therapies in view of the absence of comparative data and given the absence of predictive factors for treatment response. According to the guidelines, bDMARDs can be preferred as second-line therapy given the greater experience with their use and long-term safety data from registries.

The Committee recommends that new chemical agents targeting janus kinases should preferably be used as third or later-line treatment (i.e., after the failure of at least one biologic therapy).

Role of the medicinal product in the care pathway

In accordance with its MA, RINVOQ (upadacitinib) could be used following the failure of one or more DMARDs, either as second-line treatment (following the failure of a conventional DMARD such as methotrexate) or as third-line treatment (failure of a biologic) or later-line treatment (failure of several conventional DMARDs and/or biologics).

However, considering concerns in terms of safety, particularly long-term, related to the new action mechanism of JAK inhibitors first of all, and, secondly, the greater experience in terms of efficacy and safety of biologics, the Committee recommends that, like OLUMIANT (baricitinib) and XELJANZ (tofacitinib), RINVOQ (upadacitinib) should preferably be used as third or later-line therapy (i.e., following the failure of at least one biologic therapy).

The Committee considers that combination with methotrexate should be favoured and that monotherapy should be reserved for situations of intolerance to MTX or when continued treatment with MTX is inappropriate.