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Causality: well established
Causality assessment · Causality: well established
Bortezomib (proteasome inhibitors) and Peripheral neuropathy: is the FAERS signal real?
A written Bradford Hill assessment of one drug–event pair. The grade is a judgement about the signal, not a statement that this drug causes this event in any one person; FAERS counts are reports, not rates.
Bortezomib (proteasome inhibitors) ↔ Peripheral neuropathy
n=6,473 co-reports · PRR 17.3 · ROR 18.6
Bortezomib, a proteasome inhibitor used in multiple myeloma, commonly causes a painful peripheral neuropathy that is dose-limiting and can be severe, though it often improves after dose reduction or when treatment is stopped. The risk is higher with intravenous than subcutaneous administration and with longer treatment. The very high FAERS count (6,473 co-reports, PRR 17.3) reflects both the real effect and how widely bortezomib is used in myeloma.
Regulatory basis: bortezomib prescribing information (peripheral neuropathy warning; dose-modification guidance). Established proteasome-inhibitor neuropathy literature.
| Bradford Hill viewpoint | Status | Note |
|---|---|---|
| Temporality (necessary) | met | Neuropathy develops during treatment and often improves after dose reduction or withdrawal |
| Strength | met | PRR 17 on a very large co-report count |
| Consistency | met | Reproduced across myeloma trials |
| Specificity | met | A recognised proteasome-inhibitor effect |
| Biological gradient | met | Related to dose, route (intravenous > subcutaneous), and duration |
| Plausibility | met | Nerve injury from proteasome inhibition is the proposed mechanism |
| Coherence | met | Coheres with the labelled dose-modification guidance |
| Experiment | partial | Dechallenge (dose reduction/withdrawal) usually improves it; no randomized trial |
| Analogy | met | Analogous to neuropathy from vincristine and platinum chemotherapy |
This page's own qualitative read, not an automated/citation-gated assessment.
✗ The results-posting trial that surfaced for bortezomib (NCT00833833) was a pomalidomide study, not a bortezomib comparison, so its peripheral-neuropathy counts do not speak to bortezomib; the signal rests on myeloma trials and the labelled warning rather than a mismatched trial AE table.