Evidence map›Paper›PMID 33726834›Full record

Trial reportArthritis research & therapy2021

A randomized, placebo-controlled experimental medicine study of RIPK1 inhibitor GSK2982772 in patients with moderate to severe rheumatoid arthritis.

Kathleen Weisel, Scott Berger, Katie Thorn, Peter C Taylor, Charles Peterfy, Hilary Siddall, Debra Tompson, Susanne Wang, Emilia Quattrocchi, Susan W Burriss and 2 more

Registry-linked trialOpen access · goldAbstract readMulticenter StudyRandomized Controlled Trial
In one paragraph

Trial report in Arthritis research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02858492 (A Multicenter, Randomized, Double-blind), which is not on this map. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
9.7field-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.

NCT02858492 phase2completednot on this map

A Multicenter, Randomized, Double-blind (Sponsor-unblinded), Placebo-controlled Study to Investigate the Safety and Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of GSK2982772 in Subjects With Moderate to Severe Rheumatoid Arthritis

TypeinterventionalSponsorGlaxoSmithKlineRan2016 to 2018Enrolled52ConditionsArthritis, RheumatoidArmsGSK2982772 60 mg, Placebo
3 · Its place in the literature

Who cites it

56 citing papers in PubMed, 83 citations in OpenAlex.

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  10. Mechanisms, regulation and clinical relevance of necroptosis.Nature reviews. Molecular cell biology · 2026
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  14. Targeting PANoptosis in atherosclerosis: bridging cell death mechanisms and therapy.Apoptosis : an international journal on programmed cell death · 2026
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  17. PANoptosis: A novel therapeutic target in kidney disease (Review).International journal of molecular medicine · 2025
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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

12 authors at 5 institutions in 4 countries.

Kathleen WeiselGlaxoSmithKline, Collegeville, PA, USA.
Scott BergerGlaxoSmithKline, Collegeville, PA, USA.
Katie ThornGlaxoSmithKline, Stockley Park, Uxbridge, UK.
Peter C TaylorBotnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
Charles PeterfySpire Sciences, Inc., Boca Raton, FL, USA.
Hilary SiddallGlaxoSmithKline Medicine Research Center, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK. hilary.x.siddall@gsk.com.
Debra TompsonGlaxoSmithKline Medicine Research Center, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK.
Susanne WangGlaxoSmithKline, Collegeville, PA, USA.
Emilia QuattrocchiGlaxoSmithKline, Stockley Park, Uxbridge, UK.
Susan W BurrissGlaxoSmithKline, Collegeville, PA, USA.
Jochen WalterRheumatologische Schwerpunktpraxis, Rendsburg, Germany.
Paul Peter TakGlaxoSmithKline Medicine Research Center, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK.
GlaxoSmithKline (United Kingdom) · GBGlaxoSmithKline (United States) · USCambridge University Press · GBPraxis für Hämatologie und Onkologie · DEUniversity of Oxford · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundReceptor-interacting protein kinase 1 (RIPK1) is a key mediator of inflammation through cell death and proinflammatory cytokine production. This multicenter, randomized, double-blind (sponsor-unblinded), placebo-controlled, experimental medicine study evaluated the safety, pharmacokinetics (PK), and preliminary efficacy of GSK2982772, a RIPK1 inhibitor, in moderate to severe rheumatoid arthritis (RA).

methodsPatients with moderate to severe RA who had received ≥12 weeks' stable-dose conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy were randomized (2:1) to GSK2982772 60 mg or placebo orally 2 or 3 times daily for 84 days. Safety, PK, disease activity, joint damage, and pharmacodynamic (PD) biomarkers were assessed at days 43 and 85.

resultsA total of 52 patients were randomized (placebo, 18; GSK2982772, 34). Adverse events (AEs) were reported in 13 (72%) in patients in the placebo group (n = 3 b.i.d; n = 10 t.i.d.) and 20 (61%) in the GSK2982772 group (n = 3 b.i.d; n = 17 t.i.d.). All treatment-related AEs were mild/moderate, except one severe case of alopecia areata at day 49 and retinal vein thrombosis at day 66 (which led to withdrawal from the study) in patients receiving GSK2982772 t.i.d. Disease Activity Score in 28 Joints-C-reactive protein (DAS28-CRP) scores, ACR20/50/70 response, and rates of low disease activity and remission were similar between placebo and GSK2982772 arms.

conclusionsThese results suggest that inhibition of RIPK1 activity at the GSK2982772 exposure levels evaluated do not translate into meaningful clinical improvement of RA.

trial registrationClinicalTrials.gov Identifier: NCT02858492 . Registered 8 August 2016.

Indexed as

Antirheumatic AgentsArthritis, RheumatoidBiomedical ResearchOxazepinesDouble-Blind MethodHumansReceptor-Interacting Protein Serine-Threonine KinasesTreatment OutcomeTriazolesAntirheumatic AgentsGSK2982772OxazepinesReceptor-Interacting Protein Serine-Threonine KinasesRIPK1 protein, humanTriazolesPharmacodynamicsPharmacokineticsReceptor-interacting protein kinase 1Rheumatoid arthritisRIPK1

Identifiers

PMID33726834
PMCPMC7962407
OpenAlexW3138583342

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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.