OP0182 SECUKINUMAB IN GIANT CELL ARTERITIS: THE RANDOMISED, PARALLEL-GROUP, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTRE PHASE 2 TitAIN TRIAL

Abstract

Background Little is known about glucocorticoid-sparing agents in giant cell arteritis (GCA) except for IL-6 inhibition. Secukinumab (SEC) has shown significant improvements in the signs and symptoms of IL-17A driven medical conditions such as plaque psoriasis, psoriatic arthritis, and axial spondyloarthritis.1,2 It has a favourable long-term safety profile.1,2 Objectives TitAIN is the first randomised controlled trial investigating the potential efficacy, safety, and tolerability of SEC in GCA patients (pts). Methods This phase 2, randomised, double-blind, placebo (PBO) controlled, multicentre, proof-of-concept trial enrolled pts (aged ≥50 years) with new onset (diagnosed within 6 weeks (wks) of baseline) or relapsing (diagnosed >6 wks from baseline) GCA, naïve to biological therapy. Pts were randomised (1:1) to SEC 300 mg or PBO initially administered wkly (5 doses) and every 4 wks thereafter through Wk 48 (last dose), in combination with a 26-wk prednisolone taper regimen starting from baseline. Proportion of GCA pts in sustained remission until Wk 28 was the primary endpoint assessed by a Bayesian analysis of the posterior distribution with non-responder imputation. Other key endpoints included proportion of GCA pts in sustained remission until Wk 52 (based on study data with non-responder imputation) and time to first GCA flare after baseline. Results Out of 52 randomised pts (SEC, n=27; PBO, n=25), 71.2% (n=37) completed study treatment (SEC, 81.5%; PBO, 60.0%). Overall, 42 (80.8%) pts had new onset GCA and 10 (19.2%) pts had relapsing GCA at baseline. Proportion (posterior median with 95% credibility interval) of GCA pts in sustained remission until Wk 28 was higher with SEC, 70.1% (51.6%-84.9%), than with PBO, 20.3% (12.4%-30.0%); odds ratio (posterior median with 95% credibility interval), 9.31 (3.54-26.29) ([Table 1][1]). Until Wk 52, proportion (95% confidence interval) of GCA pts in sustained remission were 59.3% (38.8%-77.6%) in SEC group and 8.0% (1.0%-26.0%) in PBO group ([Table 1][1]). Median (95% confidence interval) time to first GCA flare after baseline was not reached for GCA pts treated with SEC and was 197.0 (101.0-280.0) days for PBO ([Figure 1][2]). Overall, treatment-emergent adverse events (AEs) occurred in 98.1% (SEC vs PBO, 100.0% vs 96.0%) and serious AEs in 32.7% (SEC vs PBO, 22.2% vs 44.0%) pts. Two pts in each SEC and PBO groups had AEs that led to study drug discontinuation and 1 pt in each group had AEs that led to death (not treatment-related). There were no new or unexpected safety signals identified with SEC treatment. View this table: Table 1. Proportion of GCA patients with sustained remission (Full analysis set) until Week 28 and 52 ![Figure 1.][3] Figure 1. Kaplan-Meier plot of time to first GCA flare from baseline up to Week 52 (Full analysis set ) Conclusion SEC demonstrated a higher sustained remission rate and longer time to first GCA flare vs PBO through 52 wks in pts with GCA. This proof-of-concept phase 2 study supports further development of SEC as a potential treatment in combination with 26 wk glucocorticoid taper for pts with GCA. References [1]Mease PJ, et al. ACR Open Rheumatol. 2020;2(1):18-25 [2]Baraliakos X, et al. RMD Open. 2019;5:e001005 Disclosure of Interests Nils Venhoff Speakers bureau: AbbVie, Novartis, Bristol-Myers-Squibb, Chugai, Roche, Vifor, Consultant of: AbbVie, Chugai, Novartis, Vifor, Grant/research support from: Bristol-Myers-Squibb, Novartis, Wolfgang A. Schmidt Speakers bureau: Abbvie, Chugai, Medac, Novartis, Roche, Sanofi, Consultant of: Advisory board member: Abbvie, Chugai, GlaxoSmithKline, Novartis, Roche, Sanofi, Grant/research support from: principle investigator in GCA trials: Abbvie, GlaxoSmithKline, Novartis, Sanofi, Raoul Bergner Speakers bureau: Abbvie, Bristol Myers Squibb, Chugai, Novartis, Roche, Consultant of: Advisory board member: Gilead, GlaxoSmithKline, Vifor, Jürgen Rech Speakers bureau: Abbvie, Biogen, BMS, Chugai, GSK, Janssen, Lilly, MSD; Novartis, Roche, Sanofi, Sobi, UCB, Consultant of: Abbvie, Biogen, BMS, Chugai, GSK, Janssen, Lilly, MSD, Novartis, Roche, Sanofi, Sobi, UCB, Leonore Unger Paid instructor for: Novartis, Hans-Peter Tony Consultant of: Abbvie, BMS, Chugai, Gilead, Lilly, Novartis, Roche, Sanofi, Meryl Mendelson Shareholder of: Novartis Pharmaceuticals Corporation, Employee of: Novartis Pharmaceuticals Corporation, Christian Sieder Employee of: Novartis Pharma GmbH, Meron Maricos Employee of: Novartis Pharma GmbH, Jens Thiel Speakers bureau: Novartis, GSK, Bristol-Myers-Squibb, Roche, AstraZeneca, Vifor, Consultant of: Novartis, Janssen, GSK; research grants: Bristol-Myers-Squibb, Novartis [1]: #T1 [2]: #F1 [3]: pending:yes