Mepolizumab Demonstrates Benefit for End Organ Dysfunction in EGPA and HES

Mepolizumab demonstrated clinically meaningful improvements across a range of end-organ systems in new real-world data in patients with eosinophilic granulomatosis with polyangiitis (EGPA) and hypereosinophilic syndrome (HES).1

These findings, from one of the largest real-world analyses to date, were presented at the American College of Rheumatology (ACR) Convergence 2025, held October 24–29 in Chicago, Illinois, by David J. Silverman, MD, Regional Section Chief of Rheumatology for Colorado Permanente Medical Group and Rheumatology Course Director of the Internal Medicine Residency at Saint Joseph Hospital.

“Real-world studies of mepolizumab have shown sustained improvements in clinical outcomes such as remission, and in comorbidities such as asthma in patients with EGPA, as well as reduced numbers of patients experiencing end-organ manifestations of both EGPA and HES,” Silverman and colleagues wrote.1 “However, real-world evidence on the changes in clinical manifestations, treatment patterns, and clinical outcomes such as EOD after mepolizumab initiation among patients with HES and EGPA in the US remains limited.”

Silverman and colleagues conducted a retrospective cohort study using administrative claims and EHR data from Optum’s Market Clarity database. The primary outcome was end-organ dysfunction (EOD) proportion & rate and secondary outcome was EOD status change.

The analysis included 1102 patients with EGPA and 784 patients with HES. Among those with EGPA, 375 were mepolizumab users and 727 were chronic standard-of-care (SoC) users. Among those with HES, 198 were mepolizumab users and 586 were chronic SoC users.1

The investigators found that mepolizumab was associated with improvements across cardiac, renal, and vascular systems in EGPA and HES. Specifically, mepolizumab significantly improved EOD status compared with chronic SoC in acute kidney failure (P = .026) and chronic kidney disease stage 3 (P = .009) in patients with EGPA, and mitral regurgitation (P <.001) and venous thrombosis (P = .009) in patients with HES.1

Silverman and colleagues noted limitations including small sample sizes and low event rates, as well as a lack of data on prior DMARD or biologic use, which may have influenced observed EOD outcomes. They emphasized that results should be interpreted cautiously, as EOD definitions were based on claims markers of treatment change and healthcare use rather than diagnostic testing.

“These findings suggest treatment with mepolizumab may offer protection against end-organ manifestations, influencing outcomes such as remission, with implications for clinical practice and future research. This goes beyond outcomes demonstrated in RCTs, establishing that mepolizumab has tangible real-world benefits,” Silverman and colleagues wrote.1

In other real-world data on organ function presented at ACR Convergence, obinutuzumab continued to show efficacy and kidney-protective potential in people with lupus nephritis (LN). Patients in this cohort had more refractory disease, having progressed past prior therapies such as rituximab, belimumab, mycophenolate mofetil, or voclosporin, and began obinutuzumab with lower baseline kidney function (mean eGFR ~70 mL/min/1.73 m²).2

In this difficult-to-treat group, 40% (n = 10) of patients achieved complete remission (CR) 32% (n = 8) achieved partial remission (PR), and 28% (n = 7) did not have a response (NR) by 24 months, for around a 70% response rate consistent with pivotal trial outcomes. Proteinuria (UPCR) declined significantly over time (P <.001), while eGFR remained largely stable. Among patients achieving CR or PR, 62% maintained stable or improved kidney function over 2 years.2

Importantly, some patients who received only 1 obinutuzumab treatment cycle achieved remission, with the earliest responses at 3 months and others emerging up to 18 months later, underscoring that delayed responders may still benefit from ongoing follow-up. Baseline kidney function strongly predicted response: those with higher initial eGFR were significantly more likely to reach CR (P = .014).2

References

1. Silverman D, Barnes T, Odo N, et al. Mepolizumab Reduces End-Organ Manifestations Compared with Standard of Care in Patients with EGPA and HES: A US Real-world Analysis. Presented at: ACR Convergence 2025; October 24-29; Chicago, Illinois. Abstract #LB16

2. Toz B, Vashistha H, Furie R, et al. Long-Term Effects of Obinutuzumab on Kidney Function in Lupus Nephritis. Presented at: ACR Convergence 2025; October 24-29; Chicago, Illinois. Poster #1520