Summary

GCAptAIN was a multicenter, randomized, double-blind, placebo-controlled trial evaluating whether the addition of secukinumab (150 mg [SEC-150] or 300 mg [SEC-300] subcutaneously), a fully human monoclonal antibody selectively targeting interleukin-17A, to a 26-week glucocorticoid (GC) taper could improve sustained remission at week 52 compared with a 52-week GC taper in patients with giant cell arteritis (GCA). The primary endpoint was the proportion of patients achieving sustained remission at week 52 in the SEC-300 versus placebo groups.

A total of 353 patients were analyzed for efficacy and safety. The study population comprised more patients with new-onset GCA (66%) than relapsing GCA (34%). The proportion of female patients was higher in the SEC-300 group than in the placebo group (72% vs. 56%).

The primary endpoint did not differ significantly between the SEC-300 and placebo groups. Sustained remission at week 52 was achieved by 25.6% of patients receiving SEC-300 compared with 16.9% receiving placebo (95% CI, −1.3 to 18.8; P=0.09). Sustained clinical remission (excluding CRP) was achieved by 36% of patients in the SEC-300 group and 33% in the placebo group. Among female patients, the difference in sustained remission rates between the SEC-300 and placebo groups was 17.5%; however, this subgroup finding should be interpreted with caution.

The mean cumulative GC dose was 3158 mg in the SEC-300 group compared with 3941 mg in the placebo group (3988 mg in the SEC- 150 group and 3952 mg in the placebo group). No safety findings of concern were identified.

Overall, these results do not support the use of SEC-300 in combination with a 26-week GC taper as a treatment strategy to improve sustained remission at week 52 in GCA.

Impact on Patient Treatment and Future Perspectives

Current treatment strategies for GCA are not universally effective, highlighting the need for novel therapeutic approaches. Interleukin-17 is considered to play a role in the pathophysiology of GCA, making IL-17 blockade a biologically plausible therapeutic approach.   The results of the GCAptAIN trial do not provide evidence to support the use of SEC-300 for the treatment of GCA.

These findings contrast with those of the phase 2 TitAIN trial, in which SEC-300 combined with a 26-week GC taper resulted in sustained remission at week 52 in 59% of patients, compared with 8% in the placebo group (median cumulative GC dose was 2506 mg in the SEC-300 group and 3466 mg in the placebo group in TitAIN). The possible difference in treatment effect among female patients in GCAptAIN is of interest, particularly given the higher prevalence of GCA among women.  Further research may help clarify whether biological sex influences the response to IL-17 blockade in GCA.

References:

[1] Stone JH, Venhoff N, Buttgereit F, Dejaco C, Schmidt WA, Spiera R, Blanco R, Rubbert-Roth A, Von Frenckell C, Blockmans D, Terrier B, Tracey G, Hauge EM, Keyport MP, Ng J, Hiremath R, Fu R, Cho G, Bacher G, Thiel J, Mendelson MH. Secukinumab for Giant Cell Arteritis. NEJM Evid. 2026 Jul;5(7):EVIDoa2600112. doi: 10.1056/EVIDoa2600112. Epub 2026 Jun 3. PMID: 42234457.

[2] Venhoff N, Schmidt WA, Bergner R, Rech J, Unger L, Tony HP, Finzel S, Andreica I, Kofler DM, Weiner SM, Lamprecht P, Schulze-Koops H, App C, Pournara E, Mendelson MH, Sieder C, Maricos M, Thiel J. Safety and efficacy of secukinumab in patients with giant cell arteritis (TitAIN): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Rheumatol. 2023 Jun;5(6):e341-e350. doi: 10.1016/S2665-9913(23)00101-7. PMID: 38251601.

Composed by

PD Dr. med. Lisa Christ, Oberärztin, Inselspital