Seliciclib MTD is 400 mg in TNF-refractory RA (TRAFIC phase 1b)
In an open-label UK dose-finding trial of 15 TNF-refractory RA patients, the CDK inhibitor seliciclib’s maximum tolerated dose was 400 mg, aiming at synovial fibroblast proliferation rather than classic immune-cytokine targets alone.
Source
Targeting synovial fibroblast proliferation in rheumatoid arthritis (TRAFIC): an open-label, dose-finding, phase 1b trial
Study at a glance
- Design
- Human experiment — Phase 1b TRAFIC: non-randomised open-label Bayesian dose-finding of oral seliciclib
- N
- N=15 · Five dose cohorts; MTD 400 mg at 35% DLT target
- Population
- Adults with active RA despite ≥3 months stable anti-TNF therapy
- Outcome
- Maximum tolerated dose (dose-limiting toxicity)
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What they did
Phase 1b TRAFIC was a non-randomised, open-label, Bayesian dose-finding study in five UK NHS hospitals. Adults with active RA despite ≥3 months stable anti-TNF therapy received escalating oral seliciclib doses to estimate the MTD at a 35% dose-limiting toxicity target.
What they found
Fifteen patients enrolled across five cohorts. The MTD was 400 mg (estimated DLT probability 0.35). Authors frame seliciclib as targeting synovial fibroblast proliferation — a cell type not yet standardly targeted by RA immune therapies that face ceiling effects.
The limits
What it doesn't show
MTD-finding is not proof of clinical efficacy. Open-label n=15 cannot establish remission rates. Phase 2 efficacy questions remain after dose selection.
Key terms
- Seliciclib
- Oral CDK inhibitor tested for MTD in TNF-refractory RA.
- TRAFIC
- Trial name for targeting synovial fibroblast proliferation in RA.
- Maximum tolerated dose (MTD)
- 400 mg here, from a Bayesian continual-reassessment design.
- Synovial fibroblasts
- Joint stromal cells whose proliferation seliciclib is meant to suppress.
- TNF-refractory RA
- Active disease despite ongoing anti-TNF therapy — the enrolment setting.
Flashcards
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Quiz yourself
MTD of seliciclib here?
Common questions
What was the primary phase 1b goal?
Establish the maximum tolerated dose of seliciclib.
What MTD was reported?
400 mg.
How many patients received drug?
15 enrolled across five cohorts.
Who was eligible?
Active RA despite stable TNF-inhibitor therapy.
Why target fibroblasts?
Authors argue current RA drugs mainly target immune inflammation and hit ceiling effects; fibroblasts are a different cell target.
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