TY - JOUR
T1 - Safety and efficacy of B-cell depletion with rituximab for the treatment of systemic sclerosis–associated pulmonary arterial hypertension
T2 - A multicenter, double-blind, randomized, placebo-controlled trial
AU - NIH ASC01 Study Group
AU - Zamanian, Roham T.
AU - Badesch, David
AU - Chung, Lorinda
AU - Domsic, Robyn T.
AU - Medsger, Thomas
AU - Pinckney, Ashley
AU - Keyes-Elstein, Lynette
AU - D’Aveta, Carla
AU - Spychala, Meagan
AU - White, R. James
AU - Hassoun, Paul M.
AU - Torres, Fernando
AU - Sweatt, Andrew J.
AU - Molitor, Jerry A.
AU - Khanna, Dinesh
AU - Maecker, Holden
AU - Welch, Beverly
AU - Goldmuntz, Ellen
AU - Nicolls, Mark R.
AU - Fischer, Aryeh
AU - Domsic, Robyn
AU - Molitor, Jerry
AU - Frech, Tracy
AU - Argula, Rahu
AU - Berman-Rosenzweig, Erika
AU - Bernstein, Elana
AU - Farber, Harrison
AU - Mayes, Maureen
AU - Ford, Hubert
AU - Spiera, Robert
AU - Ajam, Ali
AU - Sood, Namita
N1 - Publisher Copyright:
Copyright © 2021 by the American Thoracic Society
PY - 2021/7/15
Y1 - 2021/7/15
N2 - Week 24, the adjusted mean change in 6MWD at 24 weeks favored the treatment arm but did not reach statistical significance (23.6 6 11.1 m vs. 0.5 6 9.7 m; P = 0.12). Although a negative study, when data through Week 48 were also considered, the estimated change in 6MWD at Week 24 was 25.5 6 8.8 m for rituximab and 0.4 6 7.4 m for placebo (P = 0.03). Rituximab treatment appeared to be safe and well tolerated. Low levels of RF (rheumatoid factor), IL-12, and IL-17 were sensitive and specific as favorable predictors of a rituximab response as measured by an improved 6MWD (receiver operating characteristic area under the curve, 0.88–0.95). Conclusions: B-cell depletion therapy is a potentially effective and safe adjuvant treatment for SSc-PAH. Future studies in these patients can confirm whether the identified biomarkers predict rituximab responsiveness. Rationale: Systemic sclerosis (SSc)–pulmonary arterial hypertension (PAH) is one of the most prevalent and deadly forms of PAH. B cells may contribute to SSc pathogenesis. Objectives: We investigated the safety and efficacy of B-cell depletion for SSc-PAH. Methods: In an NIH-sponsored, multicenter, double-blinded, randomized, placebo-controlled, proof-of-concept trial, 57 patients with SSc-PAH on stable-dose standard medical therapy received two infusions of 1,000 mg rituximab or placebo administered 2 weeks apart. The primary outcome measure was the change in 6-minute-walk distance (6MWD) at 24 weeks. Secondary endpoints included safety and invasive hemodynamics. We applied a machine learning approach to predict drug responsiveness. Measurements and Main Results: We randomized 57 subjects from 2010 to 2018. In the primary analysis, using data through.
AB - Week 24, the adjusted mean change in 6MWD at 24 weeks favored the treatment arm but did not reach statistical significance (23.6 6 11.1 m vs. 0.5 6 9.7 m; P = 0.12). Although a negative study, when data through Week 48 were also considered, the estimated change in 6MWD at Week 24 was 25.5 6 8.8 m for rituximab and 0.4 6 7.4 m for placebo (P = 0.03). Rituximab treatment appeared to be safe and well tolerated. Low levels of RF (rheumatoid factor), IL-12, and IL-17 were sensitive and specific as favorable predictors of a rituximab response as measured by an improved 6MWD (receiver operating characteristic area under the curve, 0.88–0.95). Conclusions: B-cell depletion therapy is a potentially effective and safe adjuvant treatment for SSc-PAH. Future studies in these patients can confirm whether the identified biomarkers predict rituximab responsiveness. Rationale: Systemic sclerosis (SSc)–pulmonary arterial hypertension (PAH) is one of the most prevalent and deadly forms of PAH. B cells may contribute to SSc pathogenesis. Objectives: We investigated the safety and efficacy of B-cell depletion for SSc-PAH. Methods: In an NIH-sponsored, multicenter, double-blinded, randomized, placebo-controlled, proof-of-concept trial, 57 patients with SSc-PAH on stable-dose standard medical therapy received two infusions of 1,000 mg rituximab or placebo administered 2 weeks apart. The primary outcome measure was the change in 6-minute-walk distance (6MWD) at 24 weeks. Secondary endpoints included safety and invasive hemodynamics. We applied a machine learning approach to predict drug responsiveness. Measurements and Main Results: We randomized 57 subjects from 2010 to 2018. In the primary analysis, using data through.
KW - Pulmonary hypertension
KW - Systemic sclerosis
KW - Treatment
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UR - http://www.scopus.com/inward/citedby.url?scp=85105886145&partnerID=8YFLogxK
U2 - 10.1164/rccm.202009-3481OC
DO - 10.1164/rccm.202009-3481OC
M3 - Article
C2 - 33651671
AN - SCOPUS:85105886145
SN - 1073-449X
VL - 204
SP - 209
EP - 221
JO - American journal of respiratory and critical care medicine
JF - American journal of respiratory and critical care medicine
IS - 2
ER -