ROC-SpA: IL-17i Not Superior to Cycling TNFi Post-Failure in AxSpA

Switching to an IL-17 inhibitor (IL-17i) after failure of a first TNF inhibitor (TNFi) was not superior to cycling to a second TNFi in people with axial spondyloarthritis (axSpA) in a new study.1

These findings, from the prospective, randomized, multicenter, superiority open-label phase 4 ROC-SpA (Rotation Or Change of biotherapy after first TNFi treatment failure in AxSpA patients) study were presented at the American College of Rheumatology (ACR) Convergence 2025, held October 24–29 in Chicago, Illinois, by Hubert Marotte, MD, PhD, University of Saint-Etienne, France.

“AxSpA is initially treated with non-steroidal anti-inflammatory drugs. In case of inadequate response, ACR/EULAR recommend biological disease modifying antirheumatic drugs (bDMARDs). Until 2015, TNFi were the only available option. Since then, IL-17i have also demonstrated efficacy on axSpA. The 2022 ASAS-EULAR guidance proposes switching an alternative bDMARD after TNF inhibitors failure without mandating a change of mechanism,” Marotte and colleagues wrote.1

The study enrolled 300 patients with AxSpA who had an inadequate response after 3 months of first-line TNFi therapy and were maintained on stable doses of csDMARDs, corticosteroids, or NSAIDs for at least 1 month, across 31 centers in France. Participants were randomized to receive either an IL-17i (n = 158) or a second TNFi (n = 142). The primary endpoint was the proportion of patients achieving an ASAS40 response at week 24, with secondary outcomes including ASAS40 responses at weeks 12 and 52, as well as ASAS20, partial remission rates, and ASDAS major improvement at weeks 12, 24, and 52.1

Marotte and colleagues found that the primary endpoint of IL-17i superiority was not met, with a similar ASAS40 clinical response between IL-17i (15.2%) and TNFi (14.5%) at week 24 Furthermore, there were no statistically significant differences observed between groups for other secondary endpoints.

The investigators did find trends that were in favor of IL-17i, according to the cause of failure of the first TNFi, and other subgroups. Patients who had first TNFi failure due to primary nonresponse had a trend in favor of IL-17i (odds ratio [OR] of nonresponse, 0.69 (95% CI, 0.27-1.76) while on the other hand, failures due to adverse events favored another TNFi (OR of IL-17i nonresponse, 1.49; 95% CI, 0.42-5.32). Trends favoring IL-17i were also seen in case of skin psoriasis, HLA B27 negative status, or low CRP (< 5mg/L). At week 24, the mean ASDAS decreased to 2.5 (standard deviation, 1.0) in both groups, with no difference between groups.

“In this randomized trial of AxSpA patients with inadequate response to a first TNFi, switching to an IL-17i was not superior to cycling to a second TNFi for the primary endpoint. These findings directly inform treatment sequencing after TNFi failure and provide valuable evidence to guide individualized, shared decision-making in AxSpA management,” Marotte and colleagues concluded.1

Another comparative study post TNFi, the AgAIN study (NCT04632927), whose findings were presented at the ACR Convergence looked at comparing secukinumab (Cosentyx; Novartis) with ustekinumab (Stelara; Janssen) in patients with psoriatic arthritis (PsA). At week 28, 57.1% of patients treated with secukinumab achieved a HAQ-DI response (≥0.35-point improvement) compared with 27.0% in the ustekinumab group (OR 3.647; 95% CI, 1.601–8.311; P = .002), nearly doubling response rates with IL-17 inhibition over IL12/IL23 inhibition, with secondary end points further supporting the switch to IL-17i.2

HCPLive spoke with Frank Behrens, MD, Professor and Head of Translational Rheumatology, Immunology, and Inflammation Medicine and Head of the Inflammation Clinic at Goethe-University Frankfurt, who presented the findings during the meeting.

“The question was whether I should go first to ustekinumab prior to go for a p19 IL-23 inhibitor like guselkumab and risankizumab or an IL-17. And this question was not answered yet. And we helped people and doctors to understand the value of secukinumab compared to ustekinumab in these individual patients,” Behrens said.

References

1. Dalix E, Goupille P, Wendling D, et al. Rotation or Change of Biologic After TNF blocker treatment failure for axial Spondyloarthritis. Presented at: ACR Convergence 2025; October 24-29; Chicago, Illinois. Poster #LB09.

2. Behrens F, Sternad P, Krueger K, et al. AgAIN Study: First Head-to-Head Trial of Secukinumab vs. Ustekinumab in TNFα Inhibitor-Experienced Psoriatic Arthritis Patients Reveals Better Efficacy Across Multiple Domains. Presented at: ACR Convergence 2025; October 24-29; Chicago, Illinois. Poster #LB06.