Rheumatology
RIPK1 inhibitor GSK2982772 did not beat placebo on RA activity here
Open access · cc by · source: Europe PMC
In 52 patients with moderate–severe RA on stable csDMARDs, oral GSK2982772 60 mg for 84 days was mainly assessed for safety; DAS28-CRP and ACR responses looked similar to placebo, without meaningful clinical improvement at tested exposures.
How this study connects
Role on claims
Each row is a claim on a concept or method page where this paper supports, challenges, or qualifies the statement. Roles are hand-checked — not a model guess.
GSK2982772 (RIPK1) looked similar to placebo on RA activity at tested exposures.
In a 52-patient placebo-controlled experimental-medicine study on stable csDMARDs, safety was primary and DAS28-CRP/ACR outcomes were similar between GSK2982772 and placebo — authors conclude no meaningful clinical improvement at evaluated exposures.
Evidence for the claim as stated.
Seliciclib’s MTD is 400 mg in TNF-refractory RA (TRAFIC phase 1b).
In 15 open-label patients with active RA despite TNF inhibitors, Bayesian dose-finding set seliciclib MTD at 400 mg, aiming at synovial fibroblast proliferation rather than classic immune-cytokine pathways alone.
Scope note — MTD ≠ efficacy; RIPK1 study tested clinical activity and was null at its exposures
Limits the claim's scope: a different population, assay, or outcome.
A null RIPK1 activity signal, an MTD for seliciclib, and early synovium clusters are different evidence types. Pathway interest does not transfer efficacy across programmes.
Evidence for the claim as stated.
Open questions
Tensions this paper is part of
From concept pages' “where studies disagree.” Disagreement means the same question; scope means different assays, populations, or outcomes.
A null RIPK1 activity signal, an MTD for seliciclib, and early synovium clusters are different evidence types. Pathway interest does not transfer efficacy across programmes.
Study at a glance
- Design
- RCT — Multicenter double-blind placebo-controlled experimental-medicine RCT; 2:1 drug:placebo for 84 days on stable csDMARD
- N
- N=52 · 34 GSK2982772 60 mg, 18 placebo
- Population
- Adults with rheumatoid arthritis on stable conventional DMARD therapy
- Outcome
- Safety/PK and preliminary DAS28-CRP / ACR efficacy
Structured fields used in claim comparison tables when every cited study has a complete layer.
Inspect source passages
RIPK1 inhibitor GSK2982772 did not beat placebo on RA activity here
These passages occur verbatim in the stored paper text. They support the points listed below; they do not verify every statement in the explanation.
What mechanism does GSK2982772 inhibit?
RIPK1 inhibitor GSK2982772
What trial design was used?
randomized, double-blind (sponsor-unblinded), placebo-controlled
Key findings
52 patients were randomized (34 drug, 18 placebo). Safety was the primary objective; efficacy scores and low-disease-activity/remission rates were similar between arms. Authors conclude RIPK1 inhibition at the evaluated exposures did not translate into meaningful clinical improvement.
Methodology
Multicenter randomized, double-blind (sponsor-unblinded), placebo-controlled experimental-medicine study randomized patients 2:1 to GSK2982772 60 mg or placebo orally 2–3 times daily for 84 days while on ≥12 weeks stable csDMARD therapy, assessing safety/PK and preliminary efficacy (DAS28-CRP, ACR responses).
Limitations
A null mean efficacy signal at these exposures is not proof that all RIPK1 strategies fail forever or that higher/longer regimens cannot work. Small experimental-medicine n limits precision. Safety findings still matter for pathway development.
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