RINVOQ (upadacitinib hémihydraté) - Spondyloarthrite axiale non radiographique

Key points

Approval of reimbursement for the treatment of active non-radiographic axial spondylarthritis with objective signs of inflammation among adults responding poorly to non-steroidal anti-inflammatory drugs (NSAIDs).

No therapeutic improvement for the treatment of active non-radiographic axial spondylarthritis with objective signs of inflammation among adults responding poorly to non-steroidal anti-inflammatory drugs (NSAIDs).

Role in therapeutic strategy?

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

The first-line drug treatment of axSpA is based on the use of NSAIDs (prescription on demand, tailored to the patient and symptom progression, up to the maximum dose) as a symptomatic treatment. In the event of failure to respond or poor response to an NSAID used at the maximum tolerated dose, the NSAID may be replaced with multiple trials if needed. Adjunctive treatments such as analgesics may be associated with NSAIDs for residual pain, but systemic or local corticosteroid therapy is not justified for axial forms. Synthetic conventional basic treatments (csDMARD) (e.g. methotrexate, leflunomide, sulfasalazine) only appear to be effective for forms with symptomatic treatment-refractory peripheral joint involvement. There is no evidence of their efficacy in solely axial forms, and they are not indicated for these forms. 

As a second-line approach, targeted treatments including (bDMARD) and ts(DMARD) biological treatments must be envisaged for patients whose disease is active despite the use of NSAIDs. However, in the absence of inflammation found in pathology samples and MRI investigation, these biomedicines are not indicated for nr-axSpA. There are 7 bDMARDs: 5 TNF inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), 2 IL-17A inhibitors (ixekizumab, secukinumab). At the present time, upadacitinib is the only tsDMARD to have been granted a marketing authorisation as a second-line approach for active nr-axSpA.

According to the recommendations published by the French Society of Rheumatology, TNF inhibitors are preferred as a first-line approach given the greater follow-up with this class; however, it is not possible to establish a ranking in view of the lack of a direct comparison between these agents. In the event of loss of response, primary inefficacy or intolerance to a first TNF inhibitor, replacing with a second TNF inhibitor or switching to an IL-17A inhibitor or a JAK inhibitor are deemed to be beneficial alternatives.

Role of the medicinal product

RINVOQ (upadacitinib) in the treatment of active non-radiographic axial spondylarthritis with objective signs of inflammation among adults responding poorly to NSAIDs is ranked as a third-line and subsequent approach, after failure to respond to TNF inhibitors and/or IL17A inhibitors, considering:

• the lack of comparison to TNF inhibitors even though it was feasible, meaning that the medicinal product cannot be ranked with respect to TNF inhibitors after failure to respond to NSAIDs,
• the identified therapeutic need among patients considering effects in respect of therapeutic failure, poor response, contraindications and intolerance to TNF and IL17A inhibitors,
• the exploratory nature of the analyses conducted in the subgroup of patients previously treated with a bDMARD (small sample size, 95%CI including 0),
• uncertainties in terms of long-term safety of JAK inhibitors.

Thus, the Committee recommends that:

• as a second-line treatment (patients failing to respond to NSAIDs who are bDMARD treatment-naive), preference must be given to TNF inhibitors considering the greater follow-up in terms of safety and efficacy.
• as a third-line and subsequent approach (patients failing to respond to a bDMARD), in the event of failure to respond to a TNF inhibitor or if a change of therapeutic target is envisaged, preference must be given to IL17 inhibitors.

Moreover, as per the PRAC (EMA) recommendations following the reassessment of JAK inhibitors, it is recommended to prescribe them for their marketing authorisation indications only if no suitable therapeutic alternative is available for patients over 65 years of age, current and former smokers, and in the event of increased risk of major cardiovascular disorders and cancer. They must also be used with caution in the event of pre-existing risk factors of other forms of venous thromboembolism. Upadacitinib is contraindicated during pregnancy.