Rituximab and Serious infection: is the FAERS signal real?
Rituximab ↔ Serious infection
Reporting over time (stimulated-reporting check)
No reporting spike: the pair's share of the drug's reports is fairly stable over time (busiest two years hold 19% of 4,815 reports), so stimulated reporting is unlikely to explain the signal.
Bars: reports per year as a share of all FAERS reports for this drug, 2004–2025; amber = spike year (>3× the median share, ≥50 reports). Source: openFDA count=receivedate, retrieved 2026-10-09.
Rituximab is an anti-CD20 monoclonal antibody that depletes B cells, and an increased risk of infection — including serious bacterial, fungal, and viral infections, and notably reactivation of hepatitis B and progressive multifocal leukoencephalopathy (PML) — is a labeled, mechanistic consequence of that depletion. The FDA label carries boxed warnings for PML and HBV reactivation. The population treated (lymphoma, autoimmune disease, transplant) also raises baseline infection risk, so the FAERS count mixes drug-driven and disease-driven infection, but the causal contribution of B-cell depletion itself is well established.
Regulatory basis: rituximab prescribing information (boxed warnings for progressive multifocal leukoencephalopathy and hepatitis B virus reactivation; increased risk of serious infections).
| Bradford Hill viewpoint | Status | Note |
|---|---|---|
| Temporality (necessary) | met | Infections and reactivation follow B-cell depletion after dosing |
| Strength | partial | PRR 8 — modest, because infection is common in this population generally |
| Consistency | met | Consistent across indications and trials |
| Specificity | not established | Infection is nonspecific; disease and concomitant therapy also contribute |
| Biological gradient | partial | Relates to degree/duration of B-cell depletion and repeat dosing |
| Plausibility | met | B-cell depletion impairs humoral immunity — named mechanism |
| Coherence | met | Coheres with the immunosuppression seen with other B-cell-depleting agents |
| Experiment | partial | Infection risk tracks with depletion depth; no clean randomized removal test |
| Analogy | met | Shared with other immunosuppressants/anti-CD20 therapies |
This page's own qualitative read, not an automated/citation-gated assessment.
✓ Trial evidence found — safety of rituximab in rheumatoid arthritis (NCT00443651)
| Term (as recorded) | Rituximab 1000 mg (n=401) | Rituximab 500 mg (n=176) |
|---|---|---|
| Pneumonia (serious) | 4 | 1 |
| Upper respiratory tract infection (other) | 51 | 27 |
| Urinary tract infection (other) | 45 | 15 |
The recorded infection burden is clear, but both arms received rituximab (different doses), with no placebo arm — so this shows that infections are captured clinically, not a comparator-adjusted risk. View on ClinicalTrials.gov →