RINVOQ (upadacitinib) - Spondylarthrite ankylosante

Key points

Favourable opinion for reimbursement in the treatment of active ankylosing spondylitis in adult patients who have responded inadequately to conventional therapy.

What therapeutic improvement?

No clinical added value in the therapeutic strategy.

Role in the care pathway?

The French Rheumatology Society (SFR) published guidelines on the management of patients with axial spondyloarthritis - axSpA (radiographic and non-radiographic - nr-axSpA) in 2018.

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.

The first-line medicinal treatment of axSpA is based on the use of NSAIDs (prescription on demand, adapted to the patient and the evolution of symptoms, up to the maximum dose) as a symptomatic treatment. In the event of failure or an inadequate effect of an NSAID used at the maximum tolerated dose, a switch of NSAID can be performed.

Adjuvant therapies such as analgesics can be combined with the NSAIDs for residual pain but systemic or local corticosteroid therapy is not justified in axial forms. Conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) (e.g., methotrexate, leflunomide, sulfasalazine) only appear to be effective in forms with peripheral joint involvement refractory to symptomatic treatment. Their efficacy in purely axial forms has not been demonstrated.

As second-line treatment, biologic therapies (bDMARDs) should be considered in patients with active disease despite NSAIDs. However, in the absence of inflammation demonstrated by laboratory tests or MRI, these biologic therapies are not indicated in nr-axSpA. A total of five TNF inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab) and two IL-17A inhibitors (ixekizumab, secukinumab) have an MA in active nr-axSpA in the event of failure, inadequate response, intolerance or contraindication to NSAIDs.

According to the guidelines published by the French Radiology Society (SFR), TNF inhibitors are preferred as first-line treatment given current experience; however the lack of direct comparative data between them means that it is not possible to determine a hierarchy. In the event of loss of response, primary inefficacy or intolerance to a first TNF inhibitor, a rotation to a second TNF inhibitor or a switch to an IL-17A inhibitor are alternatives deemed to be beneficial. Given its new mechanism of action, as a selective and reversible Janus kinase (JAK 1 and JAK 1/3) inhibitor, upadacitinib is a new treatment option.

It should be noted that the updated American College of Rheumatology (ACR) guidelines published in 2019 preferentially recommend rotation to a second TNF inhibitor in the event of loss of response and favour the use of secukinumab or ixekizumab in the event of primary inefficacy, intolerance or contraindication to a first TNF inhibitor, despite the low level of evidence of the guidelines.

Role in the therapeutic strategy:

RINVOQ (upadacitinib), the first JAK inhibitor and the first oral treatment available in this indication, is a new therapeutic option in the treatment of ankylosing spondylitis in patients who have responded inadequately to conventional therapy although its role is difficult to determine compared to the available alternatives (TNF inhibitor and IL17 inhibitor).

The Committee highlights that the decision to prescribe RINVOQ (upadacitinib) should take into consideration:

• uncertainties in terms of efficacy related to the absence of comparative data versus TNF inhibitors in second and later-line therapy (patients without prior bDMARD treatment) and the absence of third and later-line data (patients in whom a bDMARD has failed),
• the more limited experience in terms of safety compared to the available alternatives,
• the administration methods and patient preferences (oral versus subcutaneous or intravenous route)

Hence, the Committee recommends that:

• in second-line treatment (patients in whom NSAIDs have failed and with no prior bDMARD treatment), TNF inhibitors should be favoured given the absence of direct comparison and the greater experience in terms of tolerance and efficacy.
• in third and later-line treatment (patients in whom a bDMARD has failed), in the event of failure of a TNF inhibitor and if a change of therapeutic target is envisaged, IL17 inhibitors should be favoured in the absence of data at present relative to the efficacy of RINVOQ (upadacitinib) in this population, in contrast with IL17 inhibitors.

Special recommendations

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