Evidence map›Paper›PMID 34099646›Full record

Trial reportNature communications2021

Phase 1 double-blind randomized safety trial of the Janus kinase inhibitor tofacitinib in systemic lupus erythematosus.

Sarfaraz A Hasni, Sarthak Gupta, Michael Davis, Elaine Poncio, Yenealem Temesgen-Oyelakin, Philip M Carlucci, Xinghao Wang, Mohammad Naqi, Martin P Playford, Rishi R Goel and 29 more

2 registry-linked trialsOpen access · goldAbstract readClinical Trial, Phase IRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 121 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
121citing papers in PubMed, 3 pooled it
24.5field-weighted citation impact, top 1% 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.

NCT02535689 phase1completednot on this map

Safety of Tofacitinib, an Oral Janus Kinase Inhibitor, in Systemic Lupus Erythematosus; a Phase Ib Clinical Trial and Associated Mechanistic Studies

TypeinterventionalSponsorNational Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)Ran2015 to 2018Enrolled34ConditionsSystemic Lupus ErythematosusArmsTofacitinib, Placebo
NCT07262983 phase1recruitingnot on this mapstarted 2026, after this paper: background citation

A Pilot Study to Evaluate the Safety and Tolerability of Baricitinib in Patients With Job s Syndrome With Lupus-like Disease and/or Atopic Dermatitis

TypeinterventionalSponsorNational Institute of Allergy and Infectious Diseases (NIAID)Ran2026 to 2030Enrolled20ConditionsHyper IgE Syndrome From STAT3 Mutation, Job s Syndrome, HIES, LupusArmsbaricitinib
3 · Its place in the literature

Who cites it

121 citing papers in PubMed, 3 syntheses or guidelines pooled it, 186 citations in OpenAlex.

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61 more citing papers are in PubMed but not listed here.

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

39 authors at 7 institutions in 1 country.

Sarfaraz A HasniLupus Clinical Trials Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, MD, USA. hasnisa@mail.nih.gov.ORCID http://orcid.org/0000-0002-4164-8837
Sarthak GuptaLupus Clinical Trials Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, MD, USA.ORCID http://orcid.org/0000-0001-8255-3554
Michael DavisLupus Clinical Trials Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, MD, USA.
Elaine PoncioLupus Clinical Trials Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, MD, USA.
Yenealem Temesgen-OyelakinLupus Clinical Trials Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, MD, USA.
Philip M CarlucciSystemic Autoimmunity Branch, NIAMS, NIH, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-9729-4572
Xinghao WangSystemic Autoimmunity Branch, NIAMS, NIH, Bethesda, MD, USA.ORCID http://orcid.org/0000-0001-8264-8537
Mohammad NaqiLupus Clinical Trials Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, MD, USA.
Martin P PlayfordSection of Inflammation and Cardiometabolic Diseases, National Heart Lung and Blood Institute (NHLBI), NIH, Bethesda, MD, USA.
Rishi R GoelSystemic Autoimmunity Branch, NIAMS, NIH, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-1715-5191
Xiaobai LiNIH Clinical Center Biostatistics and Clinical Epidemiology Service, Bethesda, MD, USA.
Ann J BiehlOffice of the Clinical Director, NIAMS, NIH, Bethesda, MD, USA.
Isabel Ochoa-NavasLupus Clinical Trials Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, MD, USA.
Zerai MannaLupus Clinical Trials Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, MD, USA.
Yinghui ShiTranslational Immunology Section, NIAMS, NIH, Bethesda, MD, USA.
Donald ThomasArthritis and Pain Associates of PG County, Greenbelt, MD, USA.ORCID http://orcid.org/0000-0002-3976-3131
Jinguo ChenTrans-NIH Center for Human Immunology, Autoimmunity and Inflammation, NIH, Bethesda, MD, USA.
Angélique BiancottoTrans-NIH Center for Human Immunology, Autoimmunity and Inflammation, NIH, Bethesda, MD, USA.
Richard AppsTrans-NIH Center for Human Immunology, Autoimmunity and Inflammation, NIH, Bethesda, MD, USA.
Foo CheungTrans-NIH Center for Human Immunology, Autoimmunity and Inflammation, NIH, Bethesda, MD, USA.
Yuri KotliarovTrans-NIH Center for Human Immunology, Autoimmunity and Inflammation, NIH, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-6558-8883
Ashley L BabyakTrans-NIH Center for Human Immunology, Autoimmunity and Inflammation, NIH, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-2399-5122
Huizhi ZhouTrans-NIH Center for Human Immunology, Autoimmunity and Inflammation, NIH, Bethesda, MD, USA.
Rongye ShiTrans-NIH Center for Human Immunology, Autoimmunity and Inflammation, NIH, Bethesda, MD, USA.
Katie StaglianoTrans-NIH Center for Human Immunology, Autoimmunity and Inflammation, NIH, Bethesda, MD, USA.
Wanxia Li TsaiTranslational Immunology Section, NIAMS, NIH, Bethesda, MD, USA.
Laura VianTranslational Immunology Section, NIAMS, NIH, Bethesda, MD, USA.
Nathalia GazanigaTranslational Immunology Section, NIAMS, NIH, Bethesda, MD, USA.
Valentina GiudiceHematology Branch, NHLBI, NIH, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-7492-6848
Shajia LuTranslational Immunology Section, NIAMS, NIH, Bethesda, MD, USA.
Stephen R BrooksBiodata Mining and Discovery Section, NIAMS, NIH, Bethesda, MD, USA.
Meggan MacKayFeinstein Institute for Medical Research, Manhasset, NY, USA.
Peter GregersenFeinstein Institute for Medical Research, Manhasset, NY, USA.
Nehal N MehtaSection of Inflammation and Cardiometabolic Diseases, National Heart Lung and Blood Institute (NHLBI), NIH, Bethesda, MD, USA.
Alan T RemaleyTranslational Vascular Medicine Branch, NHLBI, NIH, Bethesda, MD, USA.
Betty DiamondFeinstein Institute for Medical Research, Manhasset, NY, USA.ORCID http://orcid.org/0000-0002-3250-3804
John J O'SheaMolecular Immunology and Inflammation Branch, NIAMS, NIH, Bethesda, MD, USA.
Massimo GadinaTranslational Immunology Section, NIAMS, NIH, Bethesda, MD, USA.
Mariana J KaplanSystemic Autoimmunity Branch, NIAMS, NIH, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-2968-0815
National Institutes of Health · USNational Institute of Arthritis and Musculoskeletal and Skin Diseases · USFeinstein Institute for Medical Research · USNational Heart Lung and Blood Institute · USCarolina Arthritis Associates · USNational Institutes of Health Clinical Center · USOffice of the Director · US

Funding

Stat transcription factors in immunoregulation and autoimmune diseaseZIAAR041159 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI O'SHEA, JOHN · 2009 to 2025
$49.3M
Center for Human Immunology ZICAI001226 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI CHERRY, JAMES · 2018 to 2025
$34.1M
Systemic AutoimmunityZIAAR041199 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI KAPLAN, MARIANA · 2014 to 2025
$32.5M
Translational Immunology research: a support for clinical immunological researchZICAR041181 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI GADINA, MASSIMO · 2009 to 2025
$31.5M
Applying Bioinformatics to Research in Immune, Muscle, and Bone DiseasesZICAR041173 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI SUN, HONG-WEI · 2021 to 2025
$10.3M
Targeting Janus kinases in the treatment of autoimmune diseaseZIAAR041106 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI O'SHEA, JOHN · 2009 to 2024
$4.8M
6 · The paper itself

Abstract

Increased risk of premature cardiovascular disease (CVD) is well recognized in systemic lupus erythematosus (SLE). Aberrant type I-Interferon (IFN)-neutrophil interactions contribute to this enhanced CVD risk. In lupus animal models, the Janus kinase (JAK) inhibitor tofacitinib improves clinical features, immune dysregulation and vascular dysfunction. We conducted a randomized, double-blind, placebo-controlled clinical trial of tofacitinib in SLE subjects (ClinicalTrials.gov NCT02535689). In this study, 30 subjects are randomized to tofacitinib (5 mg twice daily) or placebo in 2:1 block. The primary outcome of this study is safety and tolerability of tofacitinib. The secondary outcomes include clinical response and mechanistic studies. The tofacitinib is found to be safe in SLE meeting study's primary endpoint. We also show that tofacitinib improves cardiometabolic and immunologic parameters associated with the premature atherosclerosis in SLE. Tofacitinib improves high-density lipoprotein cholesterol levels (p = 0.0006, CI 95%: 4.12, 13.32) and particle number (p = 0.0008, CI 95%: 1.58, 5.33); lecithin: cholesterol acyltransferase concentration (p = 0.024, CI 95%: 1.1, -26.5), cholesterol efflux capacity (p = 0.08, CI 95%: -0.01, 0.24), improvements in arterial stiffness and endothelium-dependent vasorelaxation and decrease in type I IFN gene signature, low-density granulocytes and circulating NETs. Some of these improvements are more robust in subjects with STAT4 risk allele.

Indexed as

AdultAgedAnimalsAtherosclerosisCholesterol, HDLDouble-Blind MethodFemaleGenetic Predisposition to DiseaseHeart Disease Risk FactorsHumansJanus Kinase InhibitorsLupus Erythematosus, SystemicMaleMiddle AgedPiperidinesPyrimidinesCholesterol, HDLJanus Kinase InhibitorsPiperidinesPyrimidinesSTAT4 protein, humanSTAT4 Transcription Factortofacitinib

Identifiers

PMID34099646
PMCPMC8185103
OpenAlexW3170585551

What OpenQuestion holds

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LicenceCC BY
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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 OpenQuestion graph.