Inside 20 million FAERS reports: 57% serious, Enbrel leads, death in 1.9 million

The FDA Adverse Event Reporting System (FAERS) now contains 20,328,575 individual adverse event reports filed between 2004 and early 2026. Of those, 11,689,760 — 57.5% — are classified as serious. Death appears as an outcome in 1,859,602 reports. And two immunology drugs, Enbrel (etanercept) and Humira (adalimumab), generate more adverse event reports than any other products in the database.

This analysis processes every FAERS report in the openFDA extract, iterating through per-year files from 2004 to 2026. Each record represents a single adverse event report (individual case safety report, or ICSR), not a confirmed causal association between a drug and a reaction. FAERS is a spontaneous reporting system: it captures what was reported, not what was proven. The data includes duplicate reports, reports of events already listed in product labeling, and reports where the drug may not have caused the observed reaction.

The growth curve

Report volume grew sixfold from 2004 to 2015, crossed one million in 2015, and peaked at 1,566,148 in 2021 before declining to approximately 1.3 million in 2024–2025. The 2021 peak coincides with the COVID-19 vaccine rollout, which generated an unprecedented volume of spontaneous adverse event reports — both genuine safety signals and reports from the general public newly aware of the FAERS system.

The serious-event share has declined from 73% in 2005–2006 to approximately 53–55% in recent years. This shift reflects the growing share of consumer-initiated reports (which include more non-serious events) relative to manufacturer-submitted expedited reports (which are dominated by serious events).

The FDA receives over 2 million new FAERS reports annually when counting follow-up submissions and amendments. In August 2025, the FDA transitioned from quarterly to daily publication of FAERS data, part of a broader data modernization effort that includes implementing the ICH E2B(R3) electronic transmission standard by April 2026.

Serious outcomes: the breakdown

FAERS classifies serious events using five mutually non-exclusive outcome categories:

"Other serious" is the most common outcome category, capturing medically important events that do not result in death, hospitalization, or disability but are judged to jeopardize the patient or require intervention. Hospitalization (21.4% of all reports) is the most tangible outcome category and the one most directly linked to healthcare costs.

Death appears in 1,859,602 reports — 9.1% of the total. This figure counts reports where death was recorded as an outcome, not reports where the drug was determined to have caused death. Many death reports involve terminally ill patients receiving palliative or late-line therapy, where the death reflects disease progression rather than drug toxicity.

The most-reported drugs

Enbrel leads with 383,043 reports, followed closely by Humira (341,246) and Dupixent (337,189). These three biologics together account for over 1 million reports — 5.2% of all FAERS entries. Their high report counts reflect several factors: large patient populations (rheumatoid arthritis, psoriasis, atopic dermatitis), injectable administration routes (injection site reactions are commonly reported), long market tenure (Enbrel was approved in 1998), and intensive manufacturer pharmacovigilance obligations for TNF inhibitors.

Zantac (ranitidine) appears with 205,577 reports — a number that spiked sharply after the 2019–2020 nitrosamine contamination scare, which generated massive consumer and media-driven reporting. Revlimid (lenalidomide, 182,387 reports) reflects both its extensive use in multiple myeloma and its REMS program, which generates structured adverse event reporting.

Most-reported active substances

Tirzepatide — the active ingredient in Mounjaro and Zepbound — has already accumulated 120,983 reports despite entering the market only in 2022. This is one of the fastest report accumulation rates in FAERS history, driven by the drug's explosive prescribing growth, consumer awareness, and the intensity of GLP-1 receptor agonist media coverage.

What patients are being treated for

Note: "Product used for unknown indication" and "Drug used for unknown indication" (combined approximately 3.5 million reports) are excluded from this table. Report indications reflect what the reporter stated, not necessarily the FDA-approved indication.

Rheumatoid arthritis leads with 643,781 reports — driven by the TNF inhibitor class (Enbrel, Humira, Remicade) and subsequent mechanisms (Rinvoq, Olumiant). Multiple sclerosis follows at 452,210, reflecting the high report volume for interferon beta products, natalizumab (Tysabri), and dimethyl fumarate (Tecfidera).

Who is reporting

Consumers are the single largest reporter group at 45.6% — a share that has grown substantially over the past decade. This reflects the increasing accessibility of the MedWatch online reporting portal, the FAERS public dashboard (redesigned in 2023), and heightened consumer awareness driven by social media and direct-to-consumer advertising. Lawyer-initiated reports (535,402, 2.6%) are a notable feature of FAERS data that distinguishes it from other pharmacovigilance databases — these reports are often associated with litigation-related submissions.

Demographics: who is affected

The 60/40 female-to-male split reflects both the epidemiology of autoimmune diseases (which disproportionately affect women) and the inclusion of contraceptive and hormone-related products (Mirena, levonorgestrel) in the high-report-count drug list.

Geographic reporting concentration

The US accounts for 57% of all FAERS reports — more than the rest of the world combined. This reflects both the size of the US pharmaceutical market and the mandatory reporting requirements that apply to US-licensed drug manufacturers. The remaining 43% comes from international ICSR submissions, voluntary reports from other countries, and reports routed through the WHO Programme for International Drug Monitoring.

What this means for pharmacovigilance and commercial teams

1. Report volume is not risk. The drugs with the most FAERS reports are not necessarily the most dangerous — they are the most prescribed, the longest on the market, and the most intensively monitored. Enbrel's 383,000 reports reflect 28 years of market presence and a TNF inhibitor class that has been under continuous pharmacovigilance scrutiny. Comparative safety conclusions require proper pharmacoepidemiologic methods, not raw report counts.

2. The tirzepatide signal is unprecedented in speed. With 120,983 reports in roughly four years, tirzepatide is accumulating FAERS entries faster than any drug in recent memory. This does not indicate disproportionate risk, but it does signal that GLP-1 receptor agonists will face sustained regulatory and media attention. Commercial teams should expect REMS modifications, label updates, and congressional inquiries.

3. Consumer reporting has transformed the data. At 45.6% of all reports, consumers now generate more FAERS entries than physicians (22%) and other HCPs (19.7%) combined. This changes the nature of the data: consumer reports tend to describe more non-serious events, use less standardized terminology, and include more duplicate submissions. Signal detection algorithms calibrated to older, HCP-dominated data may need recalibration.

4. Death reports require clinical context. The 1.86 million death-associated reports represent 9.1% of the database but span every therapeutic area and disease severity. Oncology products (Revlimid, lenalidomide) naturally generate more death reports because they treat life-threatening conditions. Raw death-report counts should never be used as a safety metric without adjustment for disease severity, line of therapy, and patient population.

5. The daily publication shift changes the landscape. The FDA's August 2025 move to daily FAERS publication replaces the quarterly cycle and accelerates public access to adverse event data. This means that media outlets, plaintiff attorneys, and competitor intelligence teams can now monitor safety signals in near-real-time. Pharmacovigilance teams should ensure their own signal detection workflows operate at or faster than the daily publication cadence.

Sources

• FDA Adverse Event Reporting System (FAERS), openFDA extract, per-year files 2004–2026; analysis by PharmaDossier, run date 2026-06-10. Report counts represent individual case safety reports (ICSRs). Serious classification per 21 CFR 314.80 and 600.80. https://www.fda.gov/drugs/surveillance/questions-and-answers-fda-adverse-event-reporting-system-faers
• FDA, "FDA Begins Real-Time Reporting of Adverse Event Data," August 25, 2025. https://www.fda.gov/drugs/drug-safety-and-availability/fda-begins-real-time-reporting-adverse-event-data
• IntuitionLabs, "The FDA Adverse Event Reporting System (FAERS) Explained." https://intuitionlabs.ai/articles/fda-adverse-event-reporting-system
• PMC, "FDA Adverse Event Reporting System (FAERS) Essentials: A Guide to Understanding, Applying, and Interpreting Adverse Event Data." https://pmc.ncbi.nlm.nih.gov/articles/PMC12393772