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POS0197 (2021)
RESPONSIVENESS OF ULTRASOUND SYNOVITIS AND CLINICAL OUTCOMES IN PSORIATIC ARTHRITIS TREATED WITH SECUKINUMAB: DATA FROM THE ULTIMATE TRIAL
M. Boers1, P. G. Conaghan2, G. Schett3, P. Mandl4, E. Naredo5, F. Van den Bosch6, R. Burgos-Vargas7, A. M. Duggan8, P. Goyanka9, C. Gaillez10, M. A. D’agostino11
1Amsterdam UMC, Vrije Universiteit, Department of Epidemiology and Data Science, and Amsterdam Rheumatology and Immunology Center, Amsterdam, Netherlands
2University of Leeds, Rheumatology, Leeds, United Kingdom
3Friedrich Alexander University of Erlangen-Nuremberg and Universitätsklinikum Erlangen, Department of Internal Medicine 3, Erlangen, Germany
4Medical University of Vienna, Division of Rheumatology, Vienna, Austria
5Hospital Fundación Jiménez Díaz and Autónoma University, Department of Rheumatology and Joint and Bone Research Unit, Madrid, Spain
6Ghent University and Ghent University Hospital, Rheumatology, Ghent, Belgium
7Hospital General de Mexico, Department of Rheumatology, Mexico City, Mexico
8Novartis Ireland Limited, Immunology, Hepatology and Dermatology, Dublin, Ireland
9Novartis Healthcare Private Limited, Immunology, Hepatology and Dermatology, Hyderabad, India
10Novartis Pharma AG, Immunology, Hepatology and Dermatology, Basel, Switzerland
11Catholic University of Sacred Heart, Rheumatology, Roma, Italy

Background: Power Doppler ultrasonography is a sensitive imaging tool to assess synovitis in psoriatic arthritis (PsA). 1,2 ULTIMATE (NCT02662985) is the first large, randomised, double-blind placebo-controlled phase IIIb study in PsA, using ultrasound to evaluate early response to secukinumab on synovitis. The use of the standardised and reliable global EULAR-OMERACT composite ultrasound synovitis score at patient level (GLOESS) as the primary endpoint showed the early and significant benefit of secukinumab vs. placebo on synovitis at week 12. 3


Objectives: To investigate the responsiveness and discriminative validity of GLOESS compared to clinical outcomes on joints at week 12 and report ultrasound and clinical efficacy data up to week 24.


Methods: This is a 52-week study with a 12-week double-blind, placebo-controlled period followed by 12-week open-label (OL) and 6-month OL extension. All placebo patients were switched to secukinumab (300 or 150 mg) at week 12. 3 Discriminative validity of GLOESS was analysed post-hoc: within-group responsiveness was assessed by comparing its standardised response mean (SRM) to that of core set of ACR response in the initial secukinumab group over 12 and 24 weeks. Mean change from baseline up to week 12 of GLOESS was determined with mixed-effect model repeated measures analysis (MMRM) and from week 12-24 as observed. 24 week efficacy outcomes included ACR responses, HAQ-DI, PASI response and resolution of dactylitis. These outcomes were exploratory and reported either according to non-responder imputation (ACR response), or as observed (HAQ-DI, PASI response and resolution of dactylitis).


Results: Of 166 patients enrolled, a total of 155 patients (93%) completed 24 weeks of treatment (secukinumab, 79 patients 95%; placebo, 76 patients 92%). Mean change from baseline to week 24 in GLOESS was similar in the initial secukinumab and placebo-secukinumab groups. A continued improvement in GLOESS was observed in the secukinumab group, with catch-up improvement in the placebo group after switch to active therapy ( Figure 1 ). Both SRM of GLOESS and ACR core components over 12 and 24 weeks were high ( Table 1 ). Similar clinical response rates were reported for clinical joint count, skin, dactylitis and function at week 24 in secukinumab and placebo switchers groups ( Table 1 ).


Conclusion: These analyses highlight the responsiveness and high discriminative validity of GLOESS in PsA, resembling that of key clinical PsA manifestations and physical function.


REFERENCES:

[1]D’Agostino MA and Coates LC. J Rheumatol. 2019;46:337–9.

[2]Uson J, et al. Rheumatol Clin. 2018;14:27–35.

[3]D’Agostino MA, et al. Arthritis Rheumatol. 2020;72 (suppl 10).

Mean change from baseline in GLOESS by treatment through Week 24

Responsiveness of GLOESS - analysed by standardised response mean and efficacy outcomes at week 24

Standardised response mean (Initial secukinumab ) Efficacy of secukinumab
Week 0–12 (N = 83 ) Week 0–24 (N = 83 ) Responders (% ) Secukinumab week 0–24 (N = 83 ) Placebo switchers week 12–24 (N = 83 )
GLOESS 1.05 1.06 ACR20 87 74
Tender joint count 1.03 1.35 ACR50 64 49
Swollen joint count 0.91 1.18 ACR70 34 23
Patient global assessment of disease activity 1.37 1.55 HAQ-DI * 80 63
Physician global assessment of disease activity 1.59 2.39 PASI 75 † 72 59
Pain 1.32 1.53 PASI 90 † 62 45
HAQ-DI score 1.32 1.32 Resolution of dactylitis (LDI=0) 67 59

* HAQ-DI response is defined as an improvement of at least 0.35 score points compared to baseline (change ≤ −0.35)

† N value for PASI response in secukinumab and placebo groups are 36 and 33; respectively. PASI response was calculated for patients with BSA ≥ 3 %.

BSA, Body Surface Area; LDI, Leeds Dactylitis Index


Disclosure of Interests: Maarten Boers Consultant of: BMS, Novartis, Pfizer, GSK, Philip G Conaghan Speakers bureau: AbbVie, AstraZeneca, BMS, Eli Lilly, Galapagos, Gilead, Novartis and Pfizer, Consultant of: AbbVie, AstraZeneca, BMS, Eli Lilly, Galapagos, Gilead, Novartis and Pfizer, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB, Peter Mandl Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, MSD, Novartis, Roche and UCB, Grant/research support from: AbbVie, BMS, Celgene, Janssen, Eli Lilly, MSD, Novartis, Roche and UCB, Esperanza Naredo Speakers bureau: AbbVie, Roche, BMS, Pfizer, UCB, Eli Lilly, Novartis, Janssen, and Celgene, Consultant of: AbbVie, Novartis and BMS, Grant/research support from: Eli Lilly, Filip van den Bosch Speakers bureau: AbbVie, Celgene, Janssen, Eli Lilly, Galapagos, Merck, Novartis, Pfizer, and UCB Pharma, Consultant of: AbbVie, Celgene, Janssen, Eli Lilly, Galapagos, Merck, Novartis, Pfizer, and UCB Pharma, Ruben Burgos-Vargas: None declared, Anne-Marie Duggan Employee of: Novartis, Punit Goyanka Employee of: Novartis, Corine Gaillez Shareholder of: Novartis and BMS, Employee of: Novartis, Maria-Antonietta D’Agostino Speakers bureau: Sanofi, Novartis, BMS, Janssen, Celgene, Roche, AbbVie, UCB, and Eli Lilly, Consultant of: Sanofi, Novartis, BMS, Janssen, Celgene, Roche, AbbVie, UCB, and Eli Lilly

Citation: Ann Rheum Dis, volume 80, supplement 1, year 2021, page 314
Session: PsA treatment: what is new? (Poster Tours)