E087 Reduced joint synovitis assessment versus the global EULAR OMERACT synovitis score (GLOESS) to predict the response to secukinumab in patients with active psoriatic arthritis and inadequate response to conventional disease-modifying anti-rheumatic drugs: exploratory results from the ULTIMATE trial
Authors: Conaghan Philip G , D'agostino Maria-Antonietta , Boers Maarten , Naredo Esperanza , Mandl Peter , Carron Philippe , Backhaus Marina , López-Rodríguez Alejandra , Hanova Petra , Goyanka Punit , Sahoo Braja G , Gaillez Corine , Bao Weibin 
Published: April 2023

Abstract

Background/Aims
The combined use of Power Doppler and B-mode ultrasound (PDUS) allows visualisation of morphological and pathophysiological changes of the synovium. ULTIMATE (NCT02662985) was the first large, randomised, double-blind, placebo-controlled PDUS phase IIIb study in psoriatic arthritis (PsA) to demonstrate that the validated Global OMERACT EULAR Synovitis Score (GLOESS), an ultrasound score at patient level, could detect the early and continuous decrease in synovitis in a multicentre setting using different ultrasound devices and examiners. Since the ultrasound assessment for GLOESS is time-consuming owing to the number of joints assessed, we investigated the ability of various reduced joint sets to predict GLOESS.

Methods
ULTIMATE was a 52-week study of secukinumab with a 12-week, double-blind, placebo-controlled period followed by a 12-week, open-label treatment period and 6-month open-label extension period. GLOESS for 24 paired joints was calculated, with a resultant potential score ranging from 0 to 144. Based on their composite PDUS scores, highly correlated joint clusters were identified with a Spearman’s rank correlation matrix and a Clustered Image Map. Representative joints were then selected from each group by various approaches (best correlation, model optimisation, etc.) yielding several joint combinations. For these reduced joint sets, GLOESS was predicted with linear models based on data from 60% of randomly selected patients from ULTIMATE. The remaining 40% of patient data were used for model validation and diagnostics.

Results
Five models were established with reduced pairs of joint sets (9-13 pairs) for PDUS-detected synovitis. The joints included in each linear model are summarised in the Table. All five reduced joint set models demonstrated scores very close to full 48 joint GLOESS (R2 ∼0.95); models 1-3 (based on 9 joint pairs) were less accurate at predicting GLOESS than models 4 and 5 (based on 13 and 12 joint pairs, respectively) for the secukinumab cohort in the open-label part (data to be shown in poster).

Conclusion
All models of reduced joint sets for PDUS-detected synovitis predicted GLOESS well. The next steps will be to document responsiveness and ability to discriminate between active and placebo treatment.
Disclosure
P.G. Conaghan: Consultancies; P.G.C. has received consultancy fees from AbbVie, AstraZeneca, BMS, Eli Lilly, Galapagos, Janssen, Merck, Novartis and Pfizer, Stryker and UCB. Member of speakers’ bureau; P.G.C. has received speakers bureau fees from AbbVie, Novartis and Pfizer. M. D'agostino: Consultancies; M.A.D'A. has received consultancy fees from AbbVie, BMS, Celgene, Eli Lilly, Janssen, Novartis, Roche, Sanofi, and UCB. Member of speakers’ bureau; M.A.D'A. has received speakers bureau fees from AbbVie, BMS, Celgene, Eli Lilly, Janssen, Novartis, Roche, Sanofi and UCB. M. Boers: Consultancies; M.B. has received consultancy fees from Novartis. E. Naredo: Honoraria; E.N. has received honoraria for clinical trials from AbbVie, BMS and Novartis. Member of speakers’ bureau; E.N. has received speakers bureau fees from AbbVie, BMS, Celgene GmbH, Janssen, Lilly, Novartis, Pfizer, Roche and UCB. Grants/research support; E.N. has received research grants from Eli Lilly. P. Mandl: Member of speakers’ bureau; P.M. has received speakers bureau fees from AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Roche and UCB. Grants/research support; P.M. has received grant/research support from AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Roche and UCB. P. Carron: Consultancies; P.C. has received consultancy fees from AbbVie, Bristol Myers Squibb, Celgene Corporation, Eli Lilly, Gilead, Merck Sharp Dohme, Novartis, Pfizer and UCB. Member of speakers’ bureau; P.C. has received speakers bureau fees from AbbVie, Bristol Myers Squibb, Celgene Corporation, Eli Lilly, Gilead, Merck Sharp Dohme, Novartis, Pfizer and UCB. Grants/research support; P.C. has received grant/research support from Merck Sharp Dohme, Pfizer and UCB. M. Backhaus: Consultancies; M.B. has received consultancy fees from BMS, Galapagos, Jonsson, MSD, Novartis, Pfizer, Roche and UCB. Member of speakers’ bureau; M.B. has received speakers bureau fees from BMS, Galapagos, Jonsson, MSD, Novartis, Pfizer, Roche and UCB. Grants/research support; M.B. has received grant/research support from BMS, Galapagos, Jonsson, MSD, Novartis, Pfizer, Roche and UCB. A. López-Rodríguez: Consultancies; A.L.R. has received consultancy fees from Eli Lilly, GSK, Janssen, Novartis, Roche and UCB. Member of speakers’ bureau; A.L.R. has received speakers bureau fees from Eli Lilly, GSK, Janssen, Novartis, Roche and UCB. P. Hanova: Consultancies; P.H. has received consultancy fees from Novartis. P. Goyanka: Other; P.G. is an employee of Novartis. B.G. Sahoo: Other; B.G.S. is an employee of Novartis. C. Gaillez: Shareholder/stock ownership; C.G. is a shareholder of Novartis and BMS. Other; C.G. is an employee of Novartis. W. Bao: Shareholder/stock ownership; W.B. is a shareholder of Novartis. Other; W.B. is an employee of Novartis.