PT3:01 Feasibility of extrarenal systemic lupus erythematosus disease modification in GLADEL 2.0, a Latin American cohort

day (LDA7.5)at both visits, and stable immunosuppressant and hydroxychloroquine doses for the preceding 12-weeks.Results In BEAT-Lupus, patients with baseline IgA2 anti-dsD-NA >=12.5AUshowed a better response to combination therapy, increasing the overall percentage point difference (delta) from 13%-58%.This association was independently validated in the CALIBRATE trial, which showed a similar improvement in response.Bayesian posterior-probability analysis, combining data from both trials, yielded a striking 99.1% probability of clinical benefit from adding belimumab in IgA2-high patientsexceeding the 95% threshold for strong evidence (figure 1A).Conversely, in IgA2-low patients, rituximab monotherapy had ~95% probability of superior response.The proportion of patients achieving BILAG LDA5 was significantly greater in the high IgA2 anti-dsDNA group at week -36 (delta-47%, 95%CI 12%-83%,p=0.0084)and onwards, reaching 56% (95%CI 19%-93%,p=0.0031)at 52-weeks (figure 1B).Whereas differences among the low IgA2 group were minimal except at 52-weeks, when more patients achieved LDA5 in the rituximab arm (delta-49%, 95%CI 13%-85%, p=0.0074; figure 1C).Similar results were also seen in LDA7.5 response.In time-to-event analysis, the time to severe-to-moderate flares was significantly delayed only in the high IgA2 anti-dsD-NA group treated with belimumab (log-rank p=0.0481; figure 1D).No such difference was observed in the low IgA2group.Conclusions These results underpin IgA2 anti-dsDNA as a theragnostic biomarker for predicting significant clinical responses to belimumab following rituximab therapy in SLE.These findings provide a feasible enrichment strategy that has directly informed the design of the first biomarker-enriched, double-blind, placebo-controlled RCT in SLE, which is set to commence recruitment in 2026 (STRATIFY-lupus trial).