Summary

On April 8, 2025, the European Medicines Agency (EMA) approved upadacitinip for the treatment of RCA (LINK: AbbVie Announces European Commission Approval of RINVOQ® (upadacitinib) for the Treatment of Adults with Giant Cell Arteritis - Apr 8, 2025), this extension of indication is based on the data from the SELECT-GCA study now also presented in the full publication. In this phase III study, patients with new (70%) or recurrent (30%) RCA were examined. Dosing was as follows: either UPA 15mg or 7.5 mg plus a 26-week glucocorticoid taper or placebo plus a 52-week glucocorticoid taper. The primary endpoint (sustained remission i.e. no symptoms of RZA from week 12 to week 52 and adherence to the glucocorticoid taper specified in the protocol) was achieved by 46.4% with UPA 15 mg versus 29.0% with placebo (p = 0.002). UPA 15 mg was also superior in terms of cumulative steroid doses or time to relapse; UPA 7.5 mg was not more effective than placebo in any endpoint. Safety outcomes were similar in the UPA and placebo groups. Although cardiovascular risk is a potential concern with a JAK inhibitor, no serious adverse cardiovascular events occurred in the UPA groups during the 52-week observation period.

Impact on Patient Treatment and Future Perspectives

As already presented at the EULAR and ACR 2024 congresses, UPA at a dose of 15 mg - but not at 7.5 mg - with a 26-week glucocorticoid taper shows better efficacy than placebo with a 52-week glucocorticoid taper. Approval has been granted by the EMA and Swiss Medic is expected to follow. In addition to the Il6 inhibitor tocilizumab, which has already been approved for some time, we will therefore soon have a second mode of action to save steroids in RZA. It remains to be seen where this will be placed in the treatment algorithm. As with the other indications, the note “treatment only in the absence of alternatives” is likely to remain in place for RZA until further safety data on the Jak inhibitors is available. It also remains unclear, for example, how effective they are in aortitis. The advantage over the IL6 inhibitor tocilizumab is certainly that CRP is still available as a parameter for activity. There could also be a preference for UPA in patients with diverticulitis. A direct comparison of the two targets would be highly desirable. If one indirectly compares (cave no head-to-head comparison!) the remission rates against placebo in the two approval studies, tocilizumab is numerically “ahead” in the GIACTA study. All Swiss rheumatologists are invited and encouraged to document their RZA patients in the SCQM registry in order to be able to answer relevant questions (www.scqm.ch ).

References:

Blockmans D, Penn SK, Setty AR, Schmidt WA, Rubbert-Roth A, Hauge EM, Keen HI, Ishii T, Khalidi N, Dejaco C, Cid MC, Hellmich B, Liu M, Zhao W, Lagunes I, Romero AB, Wung PK, Merkel PA; SELECT-GCA Study Group

N Engl J Med. 2025 Apr 2. doi: 10.1056/NEJMoa2413449. Epub ahead of print. PMID: 40174237

Composed by

PD Dr. Christof Iking-Konert, Chefarzt Rheumatologie, Stadtspital Zürich