PMID- 35005243
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220430
IS  - 2397-1991 (Electronic)
IS  - 2397-1983 (Print)
IS  - 2397-1983 (Linking)
VI  - 6
IP  - 3
DP  - 2021 Oct 1
TI  - A Pilot Study of Dimethyl Fumarate in Pulmonary Arterial Hypertension Associated 
      with Systemic Sclerosis.
PG  - 242-246
LID - 10.1177/23971983211016196 [doi]
AB  - INTRODUCTION: Given the poor treatment options for pulmonary arterial 
      hypertension associated systemic sclerosis (SSc-PAH) patients, we sought to 
      determine clinical safety and efficacy of Dimethylfumarate (DMF), an Nrf2 
      agonist, and the effects on biomarkers of oxidative stress on SSc-PAH in an 
      exploratory interventional clinical trial. OBJECTIVES: The primary objectives 
      were to assess the safety and efficacy of treatment with DMF in patients with 
      SSc-PAH. METHODS: This was an investigator-initiated, double-blind, randomized, 
      placebo-controlled trial conducted at two sites in the United States. The primary 
      safety endpoint was the incidence of serious adverse events (SAEs) and all 
      adverse events (AEs) in DMF compared to placebo-treated patients. The primary 
      efficacy endpoint was the change in 6MWD from baseline to the end of treatment at 
      Week 24 in DMF compared to placebo-treated patients. RESULTS: Six participants 
      were randomized to either placebo (n = 2) or DMF (n = 4). Baseline demographics 
      were similar in both groups. A total of 25 adverse events (AEs) occurred in 6 
      subjects, with 14 AEs (56.0%) having occurred in DMF-treated subjects. 3 
      occurrences were identified as nausea AEs, and two participants withdrew due to 
      nausea. One participant in the placebo group was withdrawn after a 
      hospitalization SAE due to worsening of heart failure and shortness of breath 
      secondary to anemia. One participant in each group completed protocol. Subjects 
      in the DMF-treated group showed a non-significant reduced decline in 6MWD 
      (relative mean change of -7.07%) from baseline to Week 24 as compared to 
      placebo-treated subjects (relative mean change of -14.97%). CONCLUSION: Patients 
      treated for SSc-PAH with 2 and 3-drug regimens, as is now typical for these 
      patients, tolerate DMF poorly. Our small samples size did not provide power to 
      suggest efficacy. We suggest that Nrf2 is still a valid therapeutic target for 
      future trials, using better tolerated Nrf2 agonists.
FAU - Kong, Kristi
AU  - Kong K
AD  - Division of Rheumatology and Clinical Immunology, University of Pittsburgh, 
      Pittsburgh, PA.
FAU - Koontz, Diane
AU  - Koontz D
AD  - Division of Rheumatology and Clinical Immunology, University of Pittsburgh, 
      Pittsburgh, PA.
FAU - Morse, Christina
AU  - Morse C
AD  - Division of Rheumatology and Clinical Immunology, University of Pittsburgh, 
      Pittsburgh, PA.
FAU - Roth, Eileen
AU  - Roth E
AD  - Division of Rheumatology and Clinical Immunology, University of Pittsburgh, 
      Pittsburgh, PA.
FAU - Domsic, Robyn T
AU  - Domsic RT
AD  - Division of Rheumatology and Clinical Immunology, University of Pittsburgh, 
      Pittsburgh, PA.
FAU - Simon, Marc A
AU  - Simon MA
AD  - Division of Cardiology, University of Pittsburgh, Pittsburgh, PA.
FAU - Stratton, Eric
AU  - Stratton E
AD  - Division of Rheumatology, Arthritis Center, Boston University, Boston, MA.
FAU - Buchholz, Connor
AU  - Buchholz C
AD  - Division of Rheumatology, Arthritis Center, Boston University, Boston, MA.
FAU - Tobin-Finch, Kimberly
AU  - Tobin-Finch K
AD  - Division of Rheumatology, Arthritis Center, Boston University, Boston, MA.
FAU - Simms, Robert
AU  - Simms R
AD  - Division of Rheumatology, Arthritis Center, Boston University, Boston, MA.
FAU - George, M Patricia
AU  - George MP
AD  - Division of Pulmonary, Critical Care and Sleep Medicine, National Jewish Health, 
      Denver, CO.
FAU - Hassoun, Paul M
AU  - Hassoun PM
AD  - Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, 
      Baltimore, MD.
FAU - Farber, Harrison
AU  - Farber H
AD  - Division of Pulmonary, Critical Care and Sleep Medicine, Tufts Medical Center, 
      Boston, MA.
FAU - Lafyatis, Robert
AU  - Lafyatis R
AD  - Division of Rheumatology and Clinical Immunology, University of Pittsburgh, 
      Pittsburgh, PA.
LA  - eng
GR  - R21 AR069285/AR/NIAMS NIH HHS/United States
PT  - Journal Article
DEP - 20210528
PL  - England
TA  - J Scleroderma Relat Disord
JT  - Journal of scleroderma and related disorders
JID - 101685427
PMC - PMC8741170
MID - NIHMS1703215
COIS- Declaration of conflicting interests: The author(s) declared no potential 
      conflicts of interest with respect to the research, authorship, and/or 
      publication of this article.
EDAT- 2022/01/11 06:00
MHDA- 2022/01/11 06:01
PMCR- 2022/10/01
CRDT- 2022/01/10 09:30
PHST- 2022/01/10 09:30 [entrez]
PHST- 2022/01/11 06:00 [pubmed]
PHST- 2022/01/11 06:01 [medline]
PHST- 2022/10/01 00:00 [pmc-release]
AID - 10.1177_23971983211016196 [pii]
AID - 10.1177/23971983211016196 [doi]
PST - ppublish
SO  - J Scleroderma Relat Disord. 2021 Oct 1;6(3):242-246. doi: 
      10.1177/23971983211016196. Epub 2021 May 28.