Sustained improvements in patient-reported outcomes after intravenous efgartigimod in adults with primary immune thrombocytopenia in a Phase 3 clinical trial (ADVANCE IV) and the first 52 weeks in its open-label extension study (ADVANCE IV+)

Abstract Introduction Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder resulting in thrombocytopenia, bleeding, constitutional symptoms, and impaired health-related quality of life (HRQoL). Although various ITP treatment options are available, many patients do not have a sustained clinical response and require additional therapy. This unmet need is especially critical in patients with chronic ITP. Objective The efficacy and safety of intravenous (IV) efgartigimod in adults with chronic and persistent ITP were demonstrated in the ADVANCE IV trial, a phase 3 randomized, double-blinded, placebo-controlled study (RCT) (Broome et al., 2023). ADVANCE IV+ is an open-label extension (OLE) study, with up to four 52-week treatment periods (TP), which aims to evaluate the long-term safety of IV efgartigimod in participants who rolled over from the RCT. Secondary objectives of the RCT and ADVANCE IV+ include evaluation of the effects of efgartigimod treatment on HRQoL measures and patient-reported outcomes (PRO). This research reports results from exploratory analyses of HRQoL and PRO data collected during the RCT and the first 52-week treatment period (TP1) of ADVANCE IV+. Methods The 36-Item Short Form Survey (SF-36) was collected from participants at 8-week intervals throughout the RCT and OLE study. Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue and Functional Assessment of Cancer Therapy-Thrombocytopenia 6-item (FACT-Th6) surveys were collected from participants at 4-week intervals during the RCT and the first 24 weeks of the OLE and every 8 weeks thereafter. SF-36 physical component summary (PCS) and mental component summary (MCS) scores, and FACIT-Fatigue and FACT-Th6 total scores were analyzed, using a mixed model for repeated measures, to estimate mean change from RCT baseline. Results Of the 67 efgartigimod-treated participants who completed the 24-week RCT, 63 rolled over to the OLE to continue efgartigimod treatment (EFG-EFG); of these, 34 completed TP1 of the OLE. Of the 39 placebo-treated participants who completed the RCT, 38 rolled over to the OLE to initiate efgartigimod treatment (PBO-EFG); of these,15completed TP1 of the OLE. For the SF-36 PCS score, the difference versus baseline for EFG-EFG and PBO-EFG participants was 1.91 and 0.36 at the end of the RCT, increasing to 3.17 and 1.88, respectively, at the end of TP1. For SF-36 MCS, the difference versus baseline for EFG-EFG and PBO-EFG participants was 3.43 and 1.41 at the end of the RCT, increasing to 6.3 and 5.87, respectively, at the end of TP1. The difference versus baseline in FACIT-Fatigue total score for EFG-EFG and PBO-EFG participants was 1.37 and 0.42 at the end of the RCT, increasing to 4.11 and 3.04, respectively, at the end of TP1. The difference versus baseline in FACT-Th6 total score for EFG-EFG and PBO-EFG participants was 2.10 and 0.00 at the end of the RCT, increasing to 3.36 and 2.75, respectively, at the end of TP1. Conclusion HRQoL issues continue to be of paramount concern for people with ITP. Consistent with efgartigimod-treated participants in the RCT, improvements in HRQoL were observed in PBO-EFG participants who initiated efgartigimod in ADVANCE IV+. Participants who received longer-term treatment with efgartigimod (EFG-EFG) continued to demonstrate improvements in HRQoL during TP1 of ADVANCE IV+ that were initially observed during the RCT. Ongoing evaluation of EFG's benefit on HRQoL and PROs are being evaluated in the ADVANCE NEXT trial (NCT06544499). ClinicalTrials.gov ID: NCT04188379, NCT04225156