ArticleAnnals of the rheumatic diseases2021
JAK selectivity and the implications for clinical inhibition of pharmacodynamic cytokine signalling by filgotinib, upadacitinib, tofacitinib and baricitinib.
Article in Annals of the rheumatic diseases, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07249060 (Interferon Signature in Cancer Patients Treated With Anti-CTLA-4 and Anti-PD-1/PD-L1 Therapies), which is not on this map. Cited by 211 papers, 4 of them syntheses that pooled it.
What it found
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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.
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.
Interferon Signature in Cancer Patients Treated With Anti-CTLA-4 and Anti-PD-1/PD-L1 Therapies: A Multicenter, Prospective, Observational Cohort Study Comparing Cancer Patients and Non-Cancer Patients With Systemic Autoimmune Diseases
Who cites it
211 citing papers in PubMed, 4 syntheses or guidelines pooled it, 314 citations in OpenAlex.
- Pooled it
- Insights into the pathogenesis of rheumatic and immune diseases from single-cell omics.Frontiers in immunology · 2026Pooled it
- Pooled it
- Janus kinase inhibitors in atopic dermatitis: an umbrella review of meta-analyses.Frontiers in immunology · 2024Pooled it
- Povorcitinib for hidradenitis suppurativa: the randomized, double-blind, placebo-controlled STOP-HS1 and STOP-HS2 phase 3 trials.Nature medicine · 2026Trial
- AZD0449, an inhaled JAK1 inhibitor, in healthy participants and patients with mild asthma.British journal of clinical pharmacology · 2026Trial
- Safety of baricitinib in vaccinated patients with severe and critical COVID-19 sub study of the randomised Bari-SolidAct trial.EBioMedicine · 2025Trial
- Exposure-response relationships for the efficacy and safety of filgotinib and its metabolite GS-829845 in subjects with rheumatoid arthritis based on phase 2 and phase 3 studies.British journal of clinical pharmacology · 2022Trial
- Assessment of the Effect of Filgotinib on the Pharmacokinetics of Atorvastatin, Pravastatin, and Rosuvastatin in Healthy Adult Participants.Clinical pharmacology in drug development · 2022Trial
- Targeting epithelial IFN-I signaling restores barrier integrity in anti-TNF refractory Crohn's disease.Journal of Crohn's & colitis · 2026Article
- Effectiveness and safety of Janus Kinase inhibitors in patients with rheumatoid arthritis, results from a multicenter observational "real-life" GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) study.Clinical rheumatology · 2026Article
- JAK inhibitors and menstrual cycle alterations: insights from a case series of 16 female patients.Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG · 2026Article
- Signaling Pathway-Biomarker Coupling for Precision Therapy in Rheumatoid Arthritis: Mechanistic Insights, Translational Bottlenecks, and Emerging Strategies.ACR open rheumatology · 2026Review
- Evolving Landscape of Systemic Therapy for Hepatocellular Carcinoma: From Targeted Therapy and Combination Strategies to Emerging Therapies.Biomedicines · 2026Review
- Hypomethylation of GNA15 Promotes Pancreatic Ductal Adenocarcinoma Progression and Macrophage M2 Polarization via STAT3-CXCL8 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Preventive Effectiveness of Recombinant Zoster Vaccine in Rheumatoid Arthritis Patients Treated with Janus Kinase Inhibitors.Internal medicine (Tokyo, Japan) · 2026Article
- Clinical and Pharmacogenetic Factors Associated with Response to JAK Inhibitors in Patients with Rheumatoid Arthritis: A Real-World Study ofPharmaceutics · 2026Article
- Region-specific immune regulation determines differential response to JAK1 inhibition in Crohn's disease ex vivo.Journal of Crohn's & colitis · 2026Article
- Comparative Effectiveness and Safety of Tofacitinib, Filgotinib, and Upadacitinib in Ulcerative Colitis: A Multicenter Real-World Cohort Study.Advances in therapy · 2026Article
- Pure red cell aplasia in a patient with rheumatoid arthritis after JAK inhibitor exposure-diagnostic challenges.Oxford medical case reports · 2026Article
151 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveJanus kinase inhibitors (JAKinibs) are efficacious in rheumatoid arthritis (RA) with variable reported rates of adverse events, potentially related to differential JAK family member selectivity. Filgotinib was compared with baricitinib, tofacitinib and upadacitinib to elucidate the pharmacological basis underlying its clinical efficacy and safety.
methodsIn vitro JAKinib inhibition of signal transducer and activator of transcription phosphorylation (pSTAT) was measured by flow cytometry in peripheral blood mononuclear cells and whole blood from healthy donors and patients with RA following cytokine stimulation of distinct JAK/STAT pathways. The average daily pSTAT and time above 50% inhibition were calculated at clinical plasma drug exposures in immune cells. The translation of these measures was evaluated in ex vivo-stimulated assays in phase 1 healthy volunteers.
resultsJAKinib potencies depended on cytokine stimulus, pSTAT readout and cell type. JAK1-dependent pathways (interferon (IFN)α/pSTAT5, interleukin (IL)-6/pSTAT1) were among the most potently inhibited by all JAKinibs in healthy and RA blood, with filgotinib exhibiting the greatest selectivity for JAK1 pathways. Filgotinib (200 mg once daily) had calculated average daily target inhibition for IFNα/pSTAT5 and IL-6/pSTAT1 that was equivalent to tofacitinib (5 mg two times per day), upadacitinib (15 mg once daily) and baricitinib (4 mg once daily), with the least average daily inhibition for the JAK2-dependent and JAK3-dependent pathways including IL-2, IL-15, IL-4 (JAK1/JAK3), IFNγ (JAK1/JAK2), granulocyte colony stimulating factor, IL-12, IL-23 (JAK2/tyrosine kinase 2) and granulocyte-macrophage colony-stimulating factor (JAK2/JAK2). Ex vivo pharmacodynamic data from phase 1 healthy volunteers clinically confirmed JAK1 selectivity of filgotinib.
conclusionFilgotinib inhibited JAK1-mediated signalling similarly to other JAKinibs, but with less inhibition of JAK2-dependent and JAK3-dependent pathways, providing a mechanistic rationale for its apparently differentiated efficacy:safety profile.
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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.