A concept of the new ‘Composite of Relevant Endpoints for Sjogren’s Syndrome’ (CRESS) has been developed, which enables discriminating between abatacept and placebo response in patients with this condition [1]. Additional validation analyses in independent, global, multicentre, placebo-controlled trials of biological disease-modifying antirheumatic drugs (DMARDs) will be performed.
Dr. Suzanne Arends (University Medical Center Groningen, the Netherlands) et al. aimed to develop a composite endpoint for primary Sjogren’s syndrome based on expert opinion and analysis of trial data. A total of 5 items were found to be most relevant to assess the effect of treatment in primary Sjogren’s syndrome patients: ESSDAI, ESSPRI, OSS, SWS, and RF/IgG.
These 5 items were tested using data at week 24 of the randomized, double blind, placebo-controlled ASAP-III trial [2]. ROC analysis was used to assess the discrimination of effect between abatacept (n=40) and placebo (n=39) treatment groups. The optimal cut-off point per item was defined by the highest sum of sensitivity and specificity. For ESSDAI, ROC analysis showed that both absolute and relative change in ESSDAI were not able to discriminate between treatment groups and no optimal cut-off point could be identified.
According to an in systemic lupus erythematosus developed endpoint [3] and based on expert opinion, it was decided to aim for the validated definition of low disease activity (ESSDAI<5) [3]. For ESSPRI, ROC analysis showed an optimal cut-off point of -13.8% which resulted in the validated definition of ESSPRI response (≥-15% or 1 point) to be used. For OSS and SWS, ROC analysis could not identify an optimal cut-off point, so the definitions based on expert opinion were kept. For serological items, ROC analysis showed optimal cut-off points of -23% and -2.2%, respectively. These numbers were to decrease ≥25% in RF or decrease ≥5% in IgG.
Taken together, responding to ≥3 of the 5 listed items discriminated best between the abatacept and placebo groups. The final response rate to the composite endpoint (CRESS responders) was 55% versus 13% in the abatacept and placebo groups, respectively.
References:
1. Arends S, et al. Composite of relevant endpoints for Sjögren’s syndrome (CRESS). SAT0170. EULAR 2020.
2. van Nimwegen JF, et al. Abatacept treatment for patients with early active primary Sjögren's syndrome: a single-centre, randomised, double-blind, placebo-controlled, phase 3 trial (ASAP-III study). Lancet Rheumatol 2020. Published online January 31, 2020.
3. Seror R, et al. Defining Disease Activity States and Clinically Meaningful Improvement in Primary Sjögren's Syndrome With EULAR Primary Sjögren's Syndrome Disease Activity (ESSDAI) and Patient-Reported Indexes (ESSPRI). Ann Rheum Dis. 2016;75(2):382-9.