Pos0298 the Mars Study: A Single-Arm, Multi-Centre Study to Assess the Long-Term (≥96 Weeks) Safety and Effectiveness of Mepolizumab in Patients With Eosinophilic Granulomatosis With Polyangiitis in Japan

Background: Considered a rare disease, eosinophilic granulomatosis with polyangiitis (EGPA) is associated with high symptom burden, that impacts quality of life, and high-dose oral corticosteroid (OCS) use. Mepolizumab is efficacious and well tolerated. However, long-term, real-world safety and effectiveness data are lacking globally. Objectives: Assess the long-term (≥96 weeks) safety and effectiveness of mepolizumab in a real-world setting in patients with EGPA in Japan. Methods: This was a single-arm, multi-centre, prospective, non-interventional, observational study of patients in a real-world setting receiving long-term treatment with 300mg subcutaneous mepolizumab every 4 weeks. Eligibility criteria included: patients aged ≥20 years, physician-diagnosed EGPA, continuous use of mepolizumab for treatment of EGPA for ≥96 weeks before study baseline (through prior registration and completion of the mepolizumab post marketing surveillance study NCT03557060). Patients were excluded if they had previously discontinued mepolizumab treatment for EGPA for >12 weeks. Patients were scheduled to continue receiving mepolizumab and data were collected during routine healthcare visits at ~12-week intervals for a 96-week observation period. Patients who discontinued mepolizumab at any time from baseline were included in the follow-up period. Primary endpoints were the frequency of adverse events (AEs) and serious AEs (SAEs). Secondary endpoints were the proportion of patients with clinical symptoms overall and as assessed across the 9 organ system; proportion of patients with EGPA relapse; annualised rate of hospitalisation and annualised rate of emergency room/unscheduled visit for EGPA treatment; average daily dose of OCS; proportion of patients in the dosing categories relative to average daily OCS. Results: A total of 118 patients were enrolled, 91% completed the study and 9% discontinued treatment. Of these, 55% were female, the mean (standard deviation SD) age was 62 (13.2) years and the mean (SD) time since diagnosis was 5.6 (4.4) years. Over 99% of patients had comorbidities at baseline (28% osteoporosis; 22% hypertension; 15% hyperlipidemia). Most patients (97%) used 300mg mepolizumab with a mean (SD) duration of 4.2 (0.68) years during the treatment period; 2 patients who continued from the MIRRA trial (NCT04551989) used mepolizumab for ≤7.4 years. AEs were reported in 69 patients (58%) and SAEs were reported in 26 patients (22%) over the observation period, infections were the most commonly reported (AEs: 36 patients 31%; SAEs: 8 patients 7%). There were no drug-related AEs. In the retrospective period, patients received a median daily OCS dose of 6.85mg (Figure 1A); 8% of patients were OCS-free. At study baseline, median daily dose was 3mg; 31% of patients were OCS-free. At the end of the observation period, median daily OCS dose was 2mg and 36% of patients were OCS-free. Overall, 68% of patients achieved a reduction in daily OCS dose to ≤4mg (50% to ≤2mg), at 96 weeks. No clinical symptoms were reported in 6% of patients in the retrospective period (Figure 1B); 27% of patients at study baseline following ≥96 weeks of mepolizumab treatment; 32% of patients at the end of the observation period (total ≥96 + ≥96 weeks mepolizumab treatment). At the end of the observation period, 12 patients (10%) had reported EGPA relapse; single (8 patients) or ≥2 (4 patients) relapses. Annualised rate (event/person–year) of EGPA-related hospitalisations decreased from 0.54 (95% confidence interval CI: 0.40–0.73) in the retrospective period to 0.02 (95% CI: 0.00–0.16) in the observation period (Table 1). Annualised rate of EGPA-related emergency room/unscheduled visit also decreased from 0.80 (95% CI: 0.53–1.19) to 0.07 (95% CI: 0.01–0.53) over the same period (Table 1). Conclusion: Mepolizumab was well tolerated after ≥96 weeks (mean SD 4.2 0.68 years) of extended use and was associated with a progressive reduction in clinical symptoms and OCS use. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: Tomonori Ishii is an employee of Tohoku University Hospital, who received funding for this study, and has also previously received funding as a speaker, consultant and for grant/research support from pharmaceutical companies, Hideaki Kunishige is an employee of, and shareholder in, GSK, Tamami Kobayashi is an employee of, and shareholder in, GSK, Etsuko Hayashi is an employee of, and shareholder in, GSK, Masaki Komatsubara is an employee of, and shareholder in, GSK, Rafael Alfonso-Cristancho is an employee of, and shareholder in, GSK, Jun Tamaoki is an employee of Tokyo Women's Medical University, who received funding from GSK for this study, Peter Howarth is an employee of, and shareholder in, GSK.