OP0130 COMPOSITE OF RELEVANT ENDPOINTS IN SJÖGREN’S SYNDROME (CRESS): A COMPREHENSIVE TOOL FOR CLINICAL TRIALS

Background: Several large randomised controlled trials (RCTs) in primary Sjögren’s syndrome (pSS) failed to demonstrate drug efficacy. 1-4 Many of these used ESSDAI as endpoint, showing but similar response rates active treatment and placebo groups. 1,3,4 Given the heterogeneous nature pSS, there is need for a composite endpoint including multiple clinically relevant parameters. Objectives: To develop validate Composite Relevant Endpoints Syndrome (CRESS). Methods: A multidisciplinary team pSS experts selected items measurements include CRESS. Definition CRESS was based on clinical relevance, previously defined minimal important improvement (MCII) data single-centre ASAP-III (abatacept) trial. 1 validated three independent RCTs: TRACTISS (rituximab) trial 2 , multi-centre abatacept 3 ETAP (tocilizumab) 4 . were assessed at visit all four trials. Results: Five complementary form CRESS: systemic disease activity, patient-reported symptoms, tear gland, salivary gland serological item. per item presented Table 1. Total ≥3 5 items. Since not have ocular staining score or ultrasonography (SGUS) available, concise (cCRESS) developed simultaneously, leaving Schirmer’s test unstimulated whole saliva flow items, respectively. In trial, 24/40 (60%) vs. 7/39 (18%) week 24 (p<0.001). definition Items Measurements Systemic activity ClinESSDAI Score<5 (low activity) Patient-reported symptoms ESSPRI Decrease ≥1 point ≥15% Tear gland* Schirmer/OSS** -If abnormal Schirmer (≤5 mm) baseline: increase ≥5 mm -Or if OSS (≥3 points) decrease ≥2 points both Schirmer/OSS normal scores no change Salivary UWS/SGUS Increase ≥25% UWS (or 0 baseline, any increase) Or total Hocevar Serological RF/IgG RFOr ≥10% IgG responder Responder Ocular Staining Score (OSS), Unstimulated (UWS), (SGUS), Rheumatoid factor (RF), Immunoglobuline G (IgG) *Concise (cCRESS): without SGUS, respectively **Mean eyes external validation trials, cCRESS were: 33/67 (49%) rituximab 20/66 (30%) 48 (p=0.026). (without SGUS) 41/92 (45%) 30/95 (32%) (p=0.067). rheumatoid factor) 10/55 tocilizumab 13/55 (24%) (p=0.482) (Figure 1A-D). Compared MCII decrease, able approximately halve RCTs with high baseline (>5) (Figures 1E-H). Conclusion: shows lower compared MCII, which crucial demonstrating With CRESS, higher treated patients found showed negative results. confirmed that differences almost outcome measures between placebo, low rates. The well-balanced, feasible, use patients. References: [1]Van Nimwegen 2020;9913(19):1–11 [2]Bowman 2017;69(7):1440–50 [3]Baer (doi:218599) [4]Felten (doi:21846) Acknowledgements: authors would like acknowledge contributors included Disclosure Interests: Suzanne Arends: None declared, Liseth de Wolff: Jolien F. van Speakers bureau: Bristol Myers Squibb, Consultant of: Gwenny M. Verstappen: Jelle Vehof: Michele Bombardieri MedImmune, GlaxoSmithKline, Grant/research support from: Simon J. Bowman AstraZenecea/MedImmune, Celgene, Eli Lilly, Glenmark, MTPharma, Novartis, Ono, Pfizer, Takeda, UCB, XTLBio, Elena Pontarini: Alan Baer Sanofi, VielaBio, Marleen Nys Shareholder Employee Jacques-Eric Gottenberg Renaud FELTEN: Neelanjana Ray Arjan Vissink: Frans G.M. Kroese Roche Janssen-Cilag, Unrestricted grants from Hendrika Bootsma Squibb Roche, Medimmune, Union Chimique Belge,