ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: L19

Secukinumab in Giant Cell Arteritis: A Randomized, Parallel-group, Double-blind, Placebo-controlled, Multicenter Phase 2 Trial

Nils Venhoff1, Wolfgang Schmidt2, Raoul Bergner3, Jürgen Rech4, Leonore Unger5, Hans-Peter Tony6, Meryl Mendelson7, Christian Sieder8, Meron Maricos8 and Jens Thiel9, 1Department of Rheumatology and Clinical Immunology, Vasculitis Center Freiburg, Medical Center - University of Freiburg, University of Freiburg, Freiburg, Germany, 2Immanuel Krankenhaus Berlin, Medical Center for Rheumatology Berlin-Buch, Lindenberger Weg 19, 13125 Berlin, Germany, Berlin, Germany, 3Medizinische Klinik A, Klinikum der Stadt Ludwigshafen, Ludwigshafen, Germany, 4Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, 91054,, Erlangen, Germany, 5Medical Department 1, Städtisches Klinikum Dresden, Dresden, Germany, 6Department of Medicine 2, Rheumatology and Clinical Immunology Oberduerrbachertstr. 697080, Wuerzburg, Germany, 7Novartis Pharmaceuticals Corporation, East Hanover, NJ, 8Novartis Pharma GmbH, Nuremberg, Germany, 9Department of Rheumatology and Clinical Immunology, Vasculitis Center Freiburg, Medical Center - University of Freiburg, University of Freiburg, Freiburg, Germany; Division of Rheumatology and Immunology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

Meeting: ACR Convergence 2021

Date of first publication: October 22, 2021

Keywords: , , , ,

Session Information

Date: Tuesday, November 9, 2021

Title: Late-Breaking Abstracts (L16 - L21)

Session Type: Late-Breaking Abstract Session

Session Time: 11:15AM-11:30AM

Background/Purpose: 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 favorable long-term safety profile.1,2 TitAIN is the first randomized controlled trial investigating the potential efficacy, safety, and tolerability of SEC in GCA patients.

Methods: This phase 2, randomized, double-blind, placebo-controlled, multicenter, proof-of-concept trial enrolled patients (aged ≥50 years) with new onset (diagnosed within 6 weeks of baseline) or relapsing (diagnosed >6 weeks from baseline) GCA, naïve to biological therapy. Patients were randomized (1:1) to SEC 300 mg or placebo initially administered weekly (5 doses) and every 4 weeks thereafter through Week 48 (last dose), in combination with a 26-week prednisolone taper regimen starting from baseline. The proportion of GCA patients in sustained remission until Week 28 was the primary endpoint assessed by a Bayesian analysis of the posterior distribution with non-responder imputation. Other key endpoints included the proportion of GCA patients in sustained remission until Week 52 (based on study data with non-responder imputation) and time to first GCA flare after baseline.

Results: Out of 52 randomized patients (SEC, n=27; placebo, n=25), 71.2% (n=37) completed study treatment (SEC, 81.5%; placebo, 60.0%). Overall, 42 (80.8%) patients had new onset GCA and 10 (19.2%) patients had relapsing GCA at baseline. The proportion (posterior median with 95% credibility interval) of GCA patients in sustained remission until Week 28 was higher with SEC, 70.1% (51.6%-84.9%), than with placebo, 20.3% (12.4%-30.0%); odds ratio (posterior median with 95% credibility interval), 9.31 (3.54-26.29) (Figure 1a). Until Week 52, the proportion (95% confidence interval) of GCA patients in sustained remission were 59.3% (38.8%-77.6%) in SEC group and 8.0% (1.0%-26.0%) in placebo group (Figure 1b). The median (95% confidence interval) time to first GCA flare after baseline was not reached for GCA patients treated with SEC and was 197.0 (101.0-280.0) days for placebo (Figure 2). Overall, treatment-emergent adverse events (AEs) occurred in 98.1% (SEC vs placebo, 100.0% vs 96.0%) and serious AEs in 32.7% (SEC vs placebo, 22.2% vs 44.0%) patients. Two patients in each SEC and placebo group had AEs that led to study drug discontinuation and 1 patient in each group had AEs that led to death (not treatment-related). There were no new or unexpected safety signals identified with SEC treatment.

Conclusion: SEC demonstrated a higher sustained remission rate along with longer time to first GCA flare versus placebo through 52 weeks in patients with GCA. This proof-of-concept phase 2 study supports the further development of SEC as a potential treatment in combination with a 26-week glucocorticoid taper for patients 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

Figure 1.
Proportion of GCA patients in sustained remission until Week 28 in the full analysis set was assessed by a Bayesian analysis of the posterior distribution with non-responder imputation; Proportion of GCA patients in sustained remission until Week 52 in the full analysis set was based on study data with non-responder imputation. The full analysis set comprises all patients to whom study treatment has been assigned by randomization and who received at least one dose of randomized study treatment (secukinumab or placebo).
GCA, giant cell arteritis; m, number of evaluable patients; n, number of patients with a response; N, number of patients in each treatment group in the full analysis set

Figure 2: Kaplan-Meier plot of time to first GCA flare from baseline up to Week 52 (Full analysis set).
The triangles and rectangular shapes are showing the censoring/event times. The drop in the line of SEC or placebo patients is associated with an event (i.e., first post-baseline GCA flare). Patients who prematurely discontinued study treatment prior to Week 52 without having an event were censored at the time of premature discontinuation and patients who completed study treatment without having an event were censored at their last visit in the treatment phase. The full analysis set comprises all patients to whom study treatment has been assigned by randomization and who received at least one dose of randomized study treatment (SEC or placebo). Time to first GCA flare after remission refers to time from first day of study treatment until first post-baseline GCA flare.
GCA, giant cell arteritis; n, total number of patients with a response; N, number of patients in each treatment group; NE, not evaluable; SEC, secukinumab

N. Venhoff, AbbVie, 1, 6, Novartis, 1, 5, 6, Bristol-Myers-Squibb, 5, 6, Chugai, 1, 6, Roche, 6, Vifor, 1, 6; W. Schmidt, Abbvie, 1, 6, 12, Principle investigator in GCA trials, Chugai, 1, 6, Medac, 6, Novartis, 1, 6, 12, Principle investigator in GCA trials, Roche, 1, 6, Sanofi, 1, 6, 12, Principle investigator in GCA trials, GlaxoSmithKline, 1, 12, Principle investigator in GCA trials; R. Bergner, Abbvie, 6, Bristol-Myers-Squibb, 6, Chugai, 6, Novartis, 6, Roche, 6, Gilead, 1, GlaxoSmithKline, 1, Vifor, 1; J. Rech, Abbvie, 2, 6, Biogen, 2, 6, BMS, 2, 6, Chugai, 2, 6, GlaxoSmithKline, 2, 6, Janssen, 2, 6, Lilly, 2, 6, MSD, 2, 6, Novartis, 2, 6, Roche, 2, 6, Sanofi, 2, 6, Sobi, 2, 6, UCB, 2, 6; L. Unger, Novartis, 6; H. Tony, Abbvie, 1, BMS, 1, Chugai, 1, Gilead, 1, Lilly, 1, Novartis, 1, Roche, 1, Sanofi, 1; M. Mendelson, Novartis, 3, 11; C. Sieder, Novartis, 3; M. Maricos, Novartis, 3; J. Thiel, Bristol-Myers-Squibb, 5, 6, Novartis, 1, 5, 6, Janssen, 1, GSK, 1, 6, Roche, 6, AstraZeneca, 6, Vifor, 6.

To cite this abstract in AMA style:

Venhoff N, Schmidt W, Bergner R, Rech J, Unger L, Tony H, Mendelson M, Sieder C, Maricos M, Thiel J. Secukinumab in Giant Cell Arteritis: A Randomized, Parallel-group, Double-blind, Placebo-controlled, Multicenter Phase 2 Trial [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/secukinumab-in-giant-cell-arteritis-a-randomized-parallel-group-double-blind-placebo-controlled-multicenter-phase-2-trial/. Accessed .

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