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

BackgroundLittle 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.1,2ObjectivesTitAIN is the first randomised controlled trial investigating the potential efficacy, safety, and tolerability of SEC in GCA patients (pts).MethodsThis 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.ResultsOut 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). 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). 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). 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.Table 1.Proportion of GCA patients with sustained remission (Full analysis set) until Week 28 and 52Proportion of ptsSecukinumab (N=27)Placebo (N=25)Median percentage (95% credibility interval), Wk 2870.1% (51.6%, 84.9%)20.3% (12.4%, 30.0%)Percentage (95% confidence interval), Wk 5259.3% (38.8%, 77.6%)8.0% (1.0%, 26.0%)The full analysis set comprises all pts to whom study treatment has been assigned by randomisation and who received at least one dose of randomised study treatment (secukinumab or placebo).GCA, giant cell arteritis; N, number of pts in each treatment group in the full analysis set, pts, patients; Wk, WeekFigure 1.Kaplan-Meier plot of time to first GCA flare from baseline up to Week 52 (Full analysis set)ConclusionSEC 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:e001005Disclosure of InterestsNils 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