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

BackgroundThe combined use of B-mode ultrasound (US) and Power Doppler (PD; combination termed as 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 Global OMERACT EULAR Synovitis Score (GLOESS), a US score at patient level, was sensitive to detect the early and continuous decrease in synovitis in a multicenter setting using different US devices and examiners.1 However, the US assessment for GLOESS was time-consuming owing to the number of joints assessed.ObjectivesTo investigate the value of various reduced joint sets to predict the validated GLOESS score.MethodsULTIMATE was a 52-week study with a 12-week double-blind, placebo-controlled period followed by 12-week open-label (OL) treatment and 6-month OL extension period.1 In the ULTIMATE trial, GLOESS for the 24 paired joints was calculated, with a potential score ranging between 0 to 144.1 A Spearman’s rank correlation matrix and a Cluster Image Map were constructed to identify highly correlated joint clusters based on the composite PDUS scores. Based on the different approaches (best correlation, model optimization, etc.), representative joints were then selected from each group, which yielded several corresponding combinations of joints. Linear models were developed with these reduced joint sets as predictors of GLOESS, using data from 60% of patients randomly selected from the ULTIMATE study. The remaining 40% data were used for model validation and diagnostics.ResultsFive models were established with reduced pairs of joint sets (9–13 pairs). The joints included in each linear model are summarized in Table 1. All five models of reduced joint sets showed high correlation with GLOESS score of R2 ~ 0.95. Figure 1 depicts all the 5 models of reduced joint sets for PDUS-detected synovitis versus the actual GLOESS in secukinumab and placebo-secukinumab groups, with modified GLOESS scores using reduced PDUS joint sets demonstrating changes very close to that of validated GLOESS.Table 1.Joints included across five linear models, indicated by green shadingJoint pairsModel 1 (N=9)Model 2 (N=9)Model 3 (N=9)Model 4 (N=13)Model 5 (N=12)ElbowKneeMTP2WristMCP1DIP4MTP4MCP2MCP4MCP5PIP3PIP4PIP1, PIP5DIP2DIP3, DIP5MTP1MTP5ShoulderTibiotalarN, number of joint pairs used in model. DIP, distal interphalangeal; MCP, metacarpophalangeal; MTP, metatarsophalangeal;PIP, proximal interphalangealFigure 1.Reduced set of joints synovitis score vs GLOESS scoreConclusionAll 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.References[1]D’Agostino MA, et al. Rheumatology (Oxford) 2021;keab628.Disclosure of InterestsMaria-Antonietta D’Agostino Speakers bureau: AbbVie, BMS, Celgene, Eli Lilly, Janssen, Novartis, Roche, Sanofi, and UCB, Consultant of: AbbVie, BMS, Celgene, Eli Lilly, Janssen, Novartis, Roche, Sanofi, and UCB, Maarten Boers Consultant of: BMS, GSK, Novartis, Pfizer, Consultant of: BMS, GSK, Novartis and Pfizer, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Lilly, Novartis, Roche and UCB, 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, Esperanza Naredo Speakers bureau: AbbVie, BMS, Celgene GmbH, Janssen, Lilly, Novartis, Pfizer, Roche, UCB, Grant/research support from: Honoraria for clinical trials from Abbvie, BMS and Novartis; Research Grants from Lilly, Peter Mandl Speakers bureau: AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Roche and UCB., Grant/research support from: AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Roche and UCB., Philippe Carron Speakers bureau: AbbVie, Bristol Myers Squibb, Celgene Corporation, Eli Lilly, Gilead, Merck Sharp Dohme, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Bristol Myers Squibb, Celgene Corporation, Eli Lilly, Gilead, Merck Sharp Dohme, Novartis, Pfizer, and UCB, Grant/research support from: Merck Sharp Dohme, Pfizer and UCB, Marina Backhaus Speakers bureau: BMS, Gilead, Jonsson, MSD, Novartis, Pfizer, Roche and UCB, Consultant of: BMS, Gilead, Jonsson, MSD, Novartis, Pfizer, Roche, UCB, Grant/research support from: BMS, Gilead, Jonsson, MSD, Novartis, Pfizer, Roche, UCB, Alejandra López-Rodríguez Speakers bureau: Eli Lilly, GSK, Janssen, Novartis, Roche and UCB, Consultant of: Eli Lilly, GSK, Janssen, Novartis, Roche and UCB, Petra Hanova: None declared, Punit Goyanka Employee of: Novartis, Braja Gopal Sahoo Employee of: Novartis, Corine Gaillez Shareholder of: Shareholder of Novartis and BMS, Employee of: Novartis, Weibin Bao Employee of: Novartis