Secukinumab Provides Sustained Improvements in the Signs and Symptoms of Active Psoriatic Arthritis through 3 Years: Efficacy and Safety Results from a Phase 3 Trial

Philip J Mease¹, Arthur Kavanaugh², Andreas Reimold³, Hasan Tahir⁴, Juergen Rech⁵, Stephen Hall⁶, Piet Geusens^7,8, Pellet Pascale⁹, Evie Maria Delicha¹⁰, Luminita Pricop¹¹ and Shephard Mpofu¹⁰, ¹Swedish Medical Center and University of Washington, Seattle, WA, ²UC San Diego School of Medicine, La Jolla, CA, ³Dallas VA Medical Center and University of Texas Southwestern Medical Center, Dallas, TX, ⁴Barts Health NHS Trust, London, United Kingdom, ⁵Department of Internal Medicine 3 – Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany, ⁶Monash University, Melbourne, Australia, ⁷University of Hasselt, Hasselt, Belgium, ⁸Maastricht University Hospital, Maastricht, Netherlands, ⁹Novartis Pharma AG, basel, Switzerland, ¹⁰Novartis Pharma AG, Basel, Switzerland, ¹¹Novartis Pharmaceuticals Corporation, East Hanover, NJ

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: monoclonal antibodies, Psoriatic arthritis, randomized trials and safety

Session Information

Date: Sunday, November 13, 2016

Title: Spondylarthropathies and Psoriatic Arthritis – Clinical Aspects and Treatment I: Psoriatic Arthritis – Treatment

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose: Secukinumab, an anti–interleukin-17A monoclonal antibody, provided rapid and significant improvements in the key clinical domains of psoriatic arthritis (PsA) in the FUTURE 1 study (NCT01392326) with improvements sustained through 2 years.¹Here, we present efficacy and safety results through 3 years in the extension of the FUTURE 1 study.

Methods: A total of 606 adults with active PsA were randomized to receive secukinumab or placebo (PBO). Secukinumab patients (pts) received a 10 mg/kg i.v. loading dose at baseline (BL), Weeks (Wks) 2 and 4, and then either 150 mg s.c. (IV→150 mg) or 75 mg s.c. (IV→75 mg) every 4 wks. PBO was given on the same dosing schedule. At Wk 16 or Wk 24, based on Wk 16 clinical response, PBO-treated pts were re-randomized to receive secukinumab 150 or 75 mg s.c. At Wk 104, pts could enter the extension phase of the study. Efficacy results at Wk 156 are presented for pts that were originally randomized to secukinumab (n = 308). Clinical assessments at Wk 156 included: ACR20/50/70, PASI 75, DAS28-CRP, SF-36 PCS, HAQ-DI, dactylitis, and enthesitis. Multiple imputation was applied to missing binary variables. Summary statistics are based on relative frequencies for binary variables and mean (±SD) for continuous variables. Analyses stratified by anti-TNFα status (anti–TNFα-naïve and anti-TNFα inadequate response [IR]) were pre-specified and reported as observed. Safety analysis is based on exposure adjusted incidence rate (EAIR). All pts (n = 587) who received ≥1 dose of study treatment through 156 wks were included in the safety analysis.

Results: Overall, 457 of the original 606 pts entered the extension study (including 308 originally randomized to secukinumab) of which 435 pts completed 156 wks (151 pts in IV→150 mg group; 142 in IV→75 mg group; 142 in PBO → secukinumab groups). At Wk 156, ACR 20/50/70 response rates were 76.8/54.9/32.9% with IV→150 mg and 65.2/39.0/26.0% with IV→75 mg, respectively. Sustained clinical improvements through Wk 156 were observed across other clinically important domains of PsA. Improvements were sustained in both anti–TNFα-naïve and anti–TNFα-IR pts (Table). Over the entire study period (mean [± SD] exposure to secukinumab of 1025.1 ± 372.7 days) the type, incidence and severity of adverse events (AEs) were consistent with those reported previously.¹EAIRs for serious infections/infestations, candida infections, Crohn’s disease, malignant/unspecified tumors, and major adverse cardiac events with secukinumab were 1.7, 1.2, 0.1, 0.9, and 0.7 per 100 pt-years, respectively.

Conclusion: Secukinumab provided sustained improvements in signs and symptoms and multiple clinical domains of active PsA in pts who completed 3 years of therapy. Secukinumab was well tolerated with a safety profile consistent with that previously reported. References: 1. Mease PJ, et al. Arthritis Rheumatol. 2015; 67 (suppl 10).

Table. Summary of Efficacy Results at Week 156

Variables

Secukinumab

IV→150 mg

(n = 161)

Secukinumab

IV→75 mg

(n = 147)

ACR 20/50/70^a (% responders)

76.8/54.9/32.9

65.2/39.0/26.0

PASI 75^a,b (% responders)

75.6

58.6

DAS28-CRP^c, mean change (SD)

–1.94 (1.3)

–1.85 (1.5)

SF-36 PCS^c, mean change (SD)

6.0 (8.5)

5.5 (7.3)

HAQ-DI^c, mean change (SD)

–0.43 (0.6)

–0.42 (0.6)

Resolution of dactylitis^a,d (%)

88.1

86.8

Resolution of enthesitis^a,d (%)

76.7

74.8

Analysis by anti-TNFα status^c

Anti–TNFα-naïve

Anti-TNFα-IR

Secukinumab

IV→150 mg

(n = 120)

Secukinumab

IV→75 mg

(n = 110)

Secukinumab

IV→150 mg

(n = 41)

Secukinumab

IV→75 mg

(n = 37)

ACR20/50/70 (% responders)

81.0/62.9/38.8

67.3/43.0/28.0

61.5/35.9/17.9

55.6/27.8/19.4

PASI 75 (% responders)

76.2

60.0

75.0

56.3

^aMultiple imputation (missing binary variables); ^bAnalysis performed in psoriasis subset pts, i.e. pts with psoriasis ≥3% body surface area at time of randomization (n = 89 in secukinumab IV→150 mg and n = 82 in secukinumab IV→75 mg); ^cObserved data; ^dData from the pts with these symptoms at BL (dactylitis, n = 83 in secukinumab IV→150 mg and n = 77 in secukinumab IV→75 mg and enthesitis, n = 99 in secukinumab IV→150 mg and n = 91 in secukinumab IV→75 mg). ACR, American College of Rheumatology response criteria; BL, baseline; DAS28-CRP, Disease Activity Score 28 using C-reactive protein; HAQ-DI, Health Assessment Questionnaire Disability Index; IV, intravenous; n, number of pts in the extension study; PASI, Psoriasis Area-and-Severity Index; SF-36 PCS, short form-36 physical component summary

Disclosure: P. J. Mease, Abbvie, Amgen, BMS, Celgene, Crescendo Bioscience, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, UCB, 2,Abbvie, Amgen, BMS, Celgene, Crescendo Bioscience, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, UCB, 5,Abbvie, Amgen, BMS, Celgene, Crescendo Bioscience, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, UCB, 8; A. Kavanaugh, Novartis Pharmaceutical Corporation, 5; A. Reimold, AbbVie, 2; H. Tahir, Novartis, Eli Lilly, and Abbvie, 8; J. Rech, Abbvie, BMS, Celgene, Fresenius, medicap, MSD, Novartis, Pfizer, and Roche, 8; S. Hall, None; P. Geusens, Pfizer, Abbott, Lilly, Amgen, MSD, Will, Bio Minerals and Roche, 2,Pfizer, Abbott, Lilly, Amgen, MSD, Will, Bio Minerals and Roche, 8; P. Pascale, Novartis Pharmaceutical Corporation, 3,Novartis Pharmaceutical Corporation, 1; E. M. Delicha, Novartis Pharmaceutical Corporation, 1,Novartis Pharmaceutical Corporation, 3; L. Pricop, Novartis, 1,Novartis, 3; S. Mpofu, Novartis, 1,Novartis, 3.

To cite this abstract in AMA style:

Mease PJ, Kavanaugh A, Reimold A, Tahir H, Rech J, Hall S, Geusens P, Pascale P, Delicha EM, Pricop L, Mpofu S. Secukinumab Provides Sustained Improvements in the Signs and Symptoms of Active Psoriatic Arthritis through 3 Years: Efficacy and Safety Results from a Phase 3 Trial [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/secukinumab-provides-sustained-improvements-in-the-signs-and-symptoms-of-active-psoriatic-arthritis-through-3-years-efficacy-and-safety-results-from-a-phase-3-trial/. Accessed .

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