PMID- 29193819
OWN - NLM
STAT- MEDLINE
DCOM- 20171211
LR  - 20220410
IS  - 2326-5205 (Electronic)
IS  - 2326-5191 (Print)
IS  - 2326-5191 (Linking)
VI  - 69
IP  - 12
DP  - 2017 Dec
TI  - Efficacy and Safety of Selexipag in Adults With Raynaud's Phenomenon Secondary to 
      Systemic Sclerosis: A Randomized, Placebo-Controlled, Phase II Study.
PG  - 2370-2379
LID - 10.1002/art.40242 [doi]
AB  - OBJECTIVE: To determine the effect of selexipag, an oral, selective IP 
      prostacyclin receptor agonist, on the frequency of attacks of Raynaud's 
      phenomenon (RP) in patients with systemic sclerosis (SSc). METHODS: Patients with 
      SSc-related RP were randomized 1:1 to placebo (n = 38) or selexipag (n = 36) in 
      individualized doses (maximum of 1,600 mug twice daily) during a 3-week titration 
      period. The primary end point was the weekly average number of RP attacks during 
      the study maintenance period, analyzed using a Bayesian approach with a negative 
      binomial model adjusted for baseline number of RP attacks. Other outcome measures 
      included Raynaud's Condition Score (RCS), RP attack duration, and 
      treatment-emergent adverse events (AEs). RESULTS: Baseline characteristics were 
      comparable between treatment groups. For 83.3% of patients, the individualized 
      maintenance dosage of selexipag was </=800 mug twice daily. No significant 
      difference was observed between placebo and selexipag in weekly average number of 
      electronic diary (eDiary)-recorded RP attacks during the maintenance period (14.2 
      attacks during the maintenance period and 21.5 attacks during the baseline week 
      in the placebo group [n = 32] versus 18.0 attacks during the maintenance period 
      and 22.4 attacks during the baseline week in the selexipag group [n = 27]; 
      adjusted mean treatment difference of 3.4 in favor of placebo). No significant 
      treatment effect was observed on RCS or RP attack duration. In the double-blind 
      period, 86.8% of placebo-treated patients and 100% of selexipag-treated patients 
      reported >/=1 AE; 55.3% and 91.7%, respectively, reported >/=1 
      prostacyclin-associated AE. CONCLUSION: Treatment with selexipag did not reduce 
      the number of RP attacks compared with placebo. The safety profile of selexipag 
      was similar to that previously reported. This study provides important 
      information about the feasibility of eDiary reporting of RP attacks in clinical 
      trials.
CI  - (c) 2017, American College of Rheumatology.
FAU - Denton, Christopher P
AU  - Denton CP
AD  - Royal Free Hospital, London, UK.
FAU - Hachulla, Eric
AU  - Hachulla E
AD  - National Referral Centre for Rare Systemic Auto-immune Diseases, Department of 
      Internal Medicine, Hopital Huriez, University of Lille, Lille, France.
FAU - Riemekasten, Gabriela
AU  - Riemekasten G
AD  - Charite University of Medicine, Berlin, Germany.
FAU - Schwarting, Andreas
AU  - Schwarting A
AD  - Johannes Gutenberg University, Mainz, and ACURA Rheumatology Centre RLP, Bad 
      Kreuznach, Germany.
FAU - Frenoux, Jean-Marie
AU  - Frenoux JM
AD  - Actelion Pharmaceuticals Ltd., Allschwil, Switzerland.
FAU - Frey, Aline
AU  - Frey A
AD  - Actelion Pharmaceuticals Ltd., Allschwil, Switzerland.
FAU - Le Brun, Franck-Olivier
AU  - Le Brun FO
AD  - Actelion Pharmaceuticals Ltd., Allschwil, Switzerland.
FAU - Herrick, Ariane L
AU  - Herrick AL
AD  - The University of Manchester, Salford Royal NHS Foundation Trust and NIHR 
      Manchester Musculoskeletal Biomedical Research Centre, Central Manchester NHS 
      Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
CN  - Raynaud Study Investigators
LA  - eng
SI  - ClinicalTrials.gov/NCT02260557
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheumatol
JT  - Arthritis & rheumatology (Hoboken, N.J.)
JID - 101623795
RN  - 0 (Acetamides)
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Pyrazines)
RN  - 5EXC0E384L (selexipag)
SB  - IM
CIN - Arthritis Rheumatol. 2017 Dec;69(12):2256-2258. PMID: 28859256
CIN - Arthritis Rheumatol. 2018 Jun;70(6):974. PMID: 29513930
CIN - Arthritis Rheumatol. 2018 Jun;70(6):973-974. PMID: 29513932
MH  - Acetamides/*administration & dosage
MH  - Adult
MH  - Antihypertensive Agents/*administration & dosage
MH  - Bayes Theorem
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Pyrazines/*administration & dosage
MH  - Raynaud Disease/*drug therapy/etiology
MH  - Scleroderma, Systemic/*complications
MH  - Severity of Illness Index
MH  - Treatment Outcome
PMC - PMC6099416
EDAT- 2017/12/02 06:00
MHDA- 2017/12/12 06:00
PMCR- 2018/08/20
CRDT- 2017/12/02 06:00
PHST- 2017/04/21 00:00 [received]
PHST- 2017/08/22 00:00 [accepted]
PHST- 2017/12/02 06:00 [entrez]
PHST- 2017/12/02 06:00 [pubmed]
PHST- 2017/12/12 06:00 [medline]
PHST- 2018/08/20 00:00 [pmc-release]
AID - ART40242 [pii]
AID - 10.1002/art.40242 [doi]
PST - ppublish
SO  - Arthritis Rheumatol. 2017 Dec;69(12):2370-2379. doi: 10.1002/art.40242.