Evidence map›Paper›PMID 38460548›Full record

Trial reportRheumatology (Oxford, England)2024

Biomarker analysis from the phase 2b randomized placebo-controlled trial of riociguat in early diffuse cutaneous systemic sclerosis.

Dinesh Khanna, Frank Kramer, Josef Höfler, Mercedeh Ghadessi, Peter Sandner, Yannick Allanore, Christopher P Denton, Masataka Kuwana, Marco Matucci-Cerinic, Janet E Pope and 19 more

Registry-linked trialOpen access · hybridAbstract readRandomized Controlled TrialClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Rheumatology (Oxford, England), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02283762 (A Randomized, Double-Blind, Placebo-Controlled Phase II Study to Investigate the Efficacy and Safety of Riociguat in Patients With Diffuse Cutaneous Systemic Sclerosis), which is not on this map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
1.3field-weighted citation impact, top 22% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02283762 phase2completednot on this map

A Randomized, Double-Blind, Placebo-Controlled Phase II Study to Investigate the Efficacy and Safety of Riociguat in Patients With Diffuse Cutaneous Systemic Sclerosis (dcSSc)

TypeinterventionalSponsorBayerRan2015 to 2019Enrolled121ConditionsScleroderma, SystemicArmsRiociguat (Adempas, BAY63-2521), Placebo
3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 3 citations in OpenAlex.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

29 authors at 20 institutions in 12 countries.

Dinesh KhannaDivision of Rheumatology, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0003-1412-4453
Frank KramerResearch and Development, Pharmaceuticals, Bayer AG, Wuppertal, Germany.
Josef HöflerStaburo GmbH, Munich, Germany.
Mercedeh GhadessiResearch and Development, Pharmaceuticals, Bayer AG, Wuppertal, Germany.
Peter SandnerResearch and Development, Pharmaceuticals, Bayer AG, Wuppertal, Germany.
Yannick AllanoreRheumatology A Department, Cochin Hospital, APAP, Paris Descartes University, Paris, France.
Christopher P DentonDivision of Medicine, Centre for Rheumatology, University College London, London, UK.ORCID 0000-0003-3975-8938
Masataka KuwanaDepartment of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine, Tokyo, Japan.ORCID 0000-0001-8352-6136
Marco Matucci-CerinicDivision of Rheumatology, Department of Experimental and Clinical Medicine, University of Firenze, Florence, Italy.
Janet E PopeDivision of Rheumatology, Schulich School of Medicine, University of Western Ontario, London, ON, Canada.ORCID 0000-0003-1479-5302
Tatsuya AtsumiDepartment of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Radim BečvářInstitute of Rheumatology, Department of Rheumatology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.
László CzirjákDepartment of Rheumatology and Immunology, Medical School, University of Pécs, Pécs, Hungary.
Ellen De LangheLaboratory of Tissue Homeostasis and Disease, Skeletal Biology and Engineering Research Center, Division of Rheumatology, Department of Development and Regeneration, KU Leuven, University Hospitals Leuven, Leuven, Belgium.ORCID 0000-0002-4045-2146
Eric HachullaDepartment of Internal Medicine and Clinical Immunology, Referral Centre for Centre for Rare Systemic Autoimmune Diseases North and North-West of France, CHU Lille, University of Lille, Inserm, U1286 - INFINITE-Institute for Translational Research in Inflammation, Lille, France.
Tomonori IshiiClinical Research, Innovation and Education Center, Tohoku University, Sendai, Japan.
Osamu IshikawaDepartment of Dermatology, Gunma University Postgraduate School of Medicine, Maebashi, Japan.
Sindhu R JohnsonDivision of Rheumatology, Department of Medicine, Toronto Western Hospital, University Health Network, Mount Sinai Hospital, University of Toronto, Toronto Scleroderma Research Program, Toronto, ON, Canada.
Valeria RiccieriDepartment of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy.
Elena SchiopuDivision of Rheumatology, Medical College of Georgia at Augusta University, Augusta, GA, USA.
Richard M SilverDivision of Rheumatology and Immunology, Medical University of South Carolina, Charleston, SC, USA.
Vanessa SmithDepartment of Internal Medicine, Ghent University, Belgium and Department of Rheumatology, Ghent University Hospital, Belgium, and Unit for Molecular Immunology and Inflammation, VIB Inflammation Research Center, Ghent, Belgium.ORCID 0000-0001-6271-7945
Chiara StagnaroRheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Virginia SteenDivision of Rheumatology, Department of Medicine, Georgetown University Medical Center, Washington, DC, USA.
Wendy StevensDepartment of Rheumatology, St Vincent's Hospital Melbourne, Melbourne, VIC, Australia.
Gabriella SzücsDepartment of Rheumatology, University of Debrecen, Debrecen, Hungary.
Marie-Elise TruchetetDepartment of Rheumatology, CHU Bordeaux, Bordeaux, France.
Melanie WosnitzaResearch and Development, Pharmaceuticals, Bayer AG, Wuppertal, Germany.
Oliver DistlerDepartment of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.ORCID 0000-0002-0546-8310
Bayer (Germany) · DEAugusta University · USBritish Society for Rheumatology · GBCentre Hospitalier Universitaire de Bordeaux · FRCharles University · CZDélégation Paris 5 · FRGeorgetown University · USGhent University Hospital · BEGunma University · JPHokkaido University · JPInserm · FRKU Leuven · BEMedical University of South Carolina · USMount Sinai Hospital · CAMünchen Klinik Schwabing · DENippon Medical School · JPSapienza University of Rome · ITSt Vincent's Hospital Melbourne · AUTohoku University · JPUniversity of Debrecen · HU

Funding

Bayer AG and Merck Sharp & Dohme LLCGlaxoSmithKlineMerck & Co., Inc.Nippon Shinyaku Co., Ltd
6 · The paper itself

Abstract

objectiveTo examine disease and target engagement biomarkers in the RISE-SSc trial of riociguat in early diffuse cutaneous systemic sclerosis and their potential to predict the response to treatment.

methodsPatients were randomized to riociguat (n = 60) or placebo (n = 61) for 52 weeks. Skin biopsies and plasma/serum samples were obtained at baseline and week 14. Plasma cyclic guanosine monophosphate (cGMP) was assessed using radio-immunoassay. α-Smooth muscle actin (αSMA) and skin thickness were determined by immunohistochemistry, mRNA markers of fibrosis by qRT-PCR in skin biopsies, and serum CXC motif chemokine ligand 4 (CXCL-4) and soluble platelet endothelial cell adhesion molecule-1 (sPECAM-1) by enzyme-linked immunosorbent assay.

resultsBy week 14, cGMP increased by 94 (78)% with riociguat and 10 (39)% with placebo (P < 0.001, riociguat vs placebo). Serum sPECAM-1 and CXCL-4 decreased with riociguat vs placebo (P = 0.004 and P = 0.008, respectively). There were no differences in skin collagen markers between the two groups. Higher baseline serum sPECAM-1 or the detection of αSMA-positive cells in baseline skin biopsies was associated with a larger reduction of modified Rodnan skin score from baseline at week 52 with riociguat vs placebo (interaction P-values 0.004 and 0.02, respectively).

conclusionPlasma cGMP increased with riociguat, suggesting engagement with the nitric oxide-soluble guanylate cyclase-cGMP pathway. Riociguat was associated with a significant reduction in sPECAM-1 (an angiogenic biomarker) vs placebo. Elevated sPECAM-1 and the presence of αSMA-positive skin cells may help to identify patients who could benefit from riociguat in terms of skin fibrosis.

trial registrationClinicaltrials.gov, NCT02283762.

Indexed as

BiomarkersPyrazolesPyrimidinesScleroderma, DiffuseSkinAdultBiopsyCyclic GMPDouble-Blind MethodFemaleFibrosisHumansMaleMiddle AgedTreatment OutcomeBiomarkersCyclic GMPPyrazolesPyrimidinesriociguatbiomarkersdiffuse cutaneous systemic sclerosisriociguatsoluble guanylate cyclase stimulators

Identifiers

PMID38460548
PMCPMC11534119
OpenAlexW4392626511

What Socratic holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.