RINVOQ (upadacitinib) - Giant cell arteritis

The clinical benefit of RINVOQ 15 mg (upadacitinib) prolonged-release tablets is moderate only in “the treatment of giant cell arteritis, in combination with a tapering course of corticosteroids, in adult patients requiring a cortisone-sparing strategy, in the absence of appropriate alternative treatments, including tocilizumab, in the following situations:

• in the event of corticosteroid dependence at a dose of ≥ 7.5 mg/day of prednisone resulting in repeated relapses,
• when rapid, early tapering of corticosteroid therapy is necessary due to cortico-steroid intolerance or severe comorbidities (poorly controlled complicated diabetes, severe mood and psychotic disorders, severe osteoporosis associated with fractures, poorly controlled severe hypertension, etc.)”.

In giant cell arteritis, in combination with a tapering course of corticosteroids, in adult patients requiring a cortisone-sparing strategy, considering:

• evidence of the superiority of RINVOQ (upadacitinib) 15 mg in combination with a tapering course of corticosteroids over 26 weeks, in terms of sustained remission rate at 52 weeks (primary endpoint), but also sustained complete remission and complete remission at 52 weeks (ranked secondary endpoints), compared to tapering corticosteroid therapy over 52 weeks, in accordance with a dose-tapering design in line with current guidelines (PNDS [French national diagnostic and care protocol] 2024), and associated with evidence of cortisone sparing,
• evidence for quality of life and fatigue score, ranked secondary endpoints,

but taking into account:

• the absence of a direct comparison with tocilizumab, a clinically relevant comparator recommended by the PNDS 2024, in patients requiring a cortisone-sparing strategy; data from an indirect comparison, not enabling robust positioning of upadacitinib (RINVOQ) compared to tocilizumab (ROACTEMRA and biosimilars) in terms of efficacy and safety,
• uncertainties with respect to the effect size and the transposability of the findings to patients requiring a cortisone-sparing strategy (relapsed patients or those without prior therapy but at high risk from cortisone exposure), given the heterogeneity of the population included and the low number of these patients in the study, resulting in uncertainty with respect to the clinical benefit in these specific situations,
• uncertainty with respect to its impact on morbidity and mortality and on maintenance of remission beyond 52 weeks and the absence of evidence for quality of life on the SF-36 score (difference demonstrated but below the clinical relevant threshold),
• and the known safety profile of upadacitinib characterised by infectious, haematological, neoplastic and cardiovascular effects, restricting its use to situations with no suitable therapeutic alternative in accordance with the SmPC and concerning a high proportion of patients with GCA (in particular, 65 years of age and older, with cardiovascular risk factors),

the Committee deems that RINVOQ 15 mg (upadacitinib) prolonged-release tablets provide no clinical added value (CAV V) in the care pathway in the treatment of giant cell arteritis, in combination with a tapering course of corticosteroids, in patients requiring a cortisone-
sparing strategy.