RT Journal Article
SR Electronic
T1 Late Breaking Abstract - Safety and efficacy of B-cell depletion with rituximab for the treatment of systemic sclerosis-associated pulmonary arterial hypertension
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP RCT1884
DO 10.1183/13993003.congress-2019.RCT1884
VO 54
IS suppl 63
A1 Zamanian, Roham
A1 Badesch, David
A1 Chung, Lorinda
A1 Domsic, Robyn
A1 Medsger, Thomas
A1 Pinckney, Ashley
A1 Keyes-Elstein, Lynette
A1 D’Aveta, Carla
A1 Spychala, Meagan
A1 White, James
A1 Hassoun, Paul
A1 Torres, Fernando
A1 Molitor, Jerry
A1 Khanna, Dinesh
A1 Maeker, Holden
A1 Welch, Beverly
A1 Goldmuntz, Ellen
A1 Nicolls, Mark
A1 On Behalf Of Asco1 Investigators, -
YR 2019
UL http://erj.ersjournals.com/content/54/suppl_63/RCT1884.abstract
AB Background: Pulmonary arterial hypertension (PAH) is a morbid complication of systemic sclerosis (SSc). Management of SSc-PAH remains challenging and mortality is high. The postulated role of B-cells in SSc suggests a role for B-cell depletion in SSc-PAH.Methods: We conducted an NIH-sponsored proof-of-concept multicenter, double-blind, randomized controlled trial of rituximab (Rx) in SSc-PAH on stable PAH therapy. Dosing was two 1000 mg infusions 14 days apart. The primary endpoint was change in 6-minute walk distance (6MWD) at 24 weeks. Secondary endpoints included change in 6MWD at other time points, pulmonary vascular resistance (PVR), time to clinical worsening (TTCW), diffusion capacity, and SSc-specific factors.Results: Between 2010–2018, 57 subjects with similar baseline clinical characteristics were randomized 1:1 to Rx or placebo (Pc). Rx was well tolerated without unexpected toxicities. In a longitudinal analysis using data through week 24, 6MWD trended towards improvement after Rx relative to Pc, but did not differ significantly between arms (23.6±11.1m Rx, 0.5±9.7m Pc, p=0.12). A pre-specified secondary analysis using data through week 48 demonstrated improvement at week 24 (25.5±8.8m Rx, 0.4±7.4m Pc, p=0.03) with a loss of effect by week 48 (9.5±12.4m Rx, -7.0±8.6m Pc, p=0.28). Higher proportion of Pc subjects required additional PAH therapies, but changes in PVR and TTCW were not significantly different.Conclusion: Adjunctive B-cell depletion therapy is a safe and potentially effective treatment for SSc-PAH. This is the first controlled trial examining the role of immunotherapy in a serious form of PAH and warrants further study.FootnotesCite this article as: European Respiratory Journal 2019; 54: Suppl. 63, RCT1884.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).