Etanercept vs Methotrexate: side effects in FDA adverse event reports
At a glance
| Etanercept | Methotrexate | |
|---|---|---|
| Drug class | Tumor Necrosis Factor Blocker | – |
| Brand names | Enbrel | – |
| FAERS reports | 595,118 | 483,097 |
| Serious | 36% | 73% |
| Death outcome | 17,154 | 37,640 |
| Boxed warning | Yes SERIOUS INFECTIONS and MALIGNANCIES WARNING: SERIOUS INFECTIONS and MALIGNANCIES See full prescribing information for complete boxed warning. SERIOUS INFECTIONS | Yes WARNING: EMBRYO-FETAL TOXICITY, HYPERSENSITIVITY REACTIONS, BENZYL ALCOHOL TOXICITY, and OTHER SERIOUS ADVERSE REACTIONS • Methotrexate Injection can cause embr |
Signals both drugs share
| Reaction | Etanercept | Methotrexate | Label screen (A / B) |
|---|---|---|---|
| Duodenal ulcer perforation | 4,537 · PRR 56.6 | 5,067 · PRR 97.3 | Not in label — unassessed / Labeled (related wording) |
| Bone erosion | 1,731 · PRR 33.1 | 2,084 · PRR 61.7 | Not in label — unassessed / Labeled (related wording) |
| Rheumatoid nodule | 1,295 · PRR 30.1 | 1,759 · PRR 74.3 | Labeled (related wording) / Likely indication confounding |
| Granuloma skin | 513 · PRR 56.8 | 539 · PRR 80.8 | Labeled (related wording) / Not in label — unassessed |
| Synovitis | 11,207 · PRR 57.3 | 13,569 · PRR 133.8 | Not in label — unassessed / Not in label — unassessed |
| Pemphigus | 8,412 · PRR 73.6 | 9,382 · PRR 135.9 | Not in label — unassessed / Not in label — unassessed |
| Hand deformity | 8,536 · PRR 65.9 | 8,885 · PRR 92.3 | Not in label — unassessed / Not in label — unassessed |
| Helicobacter infection | 4,820 · PRR 31.1 | 5,277 · PRR 46.1 | Not in label — unassessed / Not in label — unassessed |
| Folliculitis | 4,400 · PRR 25.6 | 5,035 · PRR 40.8 | Not in label — unassessed / Not in label — unassessed |
| Muscle injury | 3,852 · PRR 30.6 | 4,306 · PRR 47.5 | Not in label — unassessed / Not in label — unassessed |
| Sleep disorder due to general medical condition, insomnia type | 3,315 · PRR 36.8 | 3,191 · PRR 42.2 | Not in label — unassessed / Not in label — unassessed |
| Rheumatic fever | 2,908 · PRR 69.9 | 3,282 · PRR 133.3 | Likely indication confounding / Likely indication confounding |
| Facet joint syndrome | 1,651 · PRR 38.2 | 1,964 · PRR 71.6 | Not in label — unassessed / Not in label — unassessed |
| Deep vein thrombosis postoperative | 1,212 · PRR 56.5 | 1,372 · PRR 101.8 | Not in label — unassessed / Not in label — unassessed |
| Dislocation of vertebra | 1,027 · PRR 29.7 | 1,211 · PRR 51.4 | Not in label — unassessed / Not in label — unassessed |
| Adjustment disorder with depressed mood | 976 · PRR 32.5 | 1,109 · PRR 52.7 | Not in label — unassessed / Not in label — unassessed |
| Lupus vulgaris | 662 · PRR 43.6 | 867 · PRR 117.7 | Not in label — unassessed / Not in label — unassessed |
| Joint destruction | 811 · PRR 37.4 | 684 · PRR 33.3 | Not in label — unassessed / Not in label — unassessed |
| Seronegative arthritis | 444 · PRR 22.6 | 555 · PRR 42.0 | Likely indication confounding / Likely indication confounding |
Labeled signals distinctive to Etanercept
- Injection site warmth — n=10,385, PRR 35.3 Labeled (related wording)
- Injection site haematoma — n=6,063, PRR 24.4 Labeled (related wording)
- Injection site recall reaction — n=486, PRR 911.8 Labeled (related wording)
- Injection site macule — n=470, PRR 74.5 Labeled (related wording)
Labeled signals distinctive to Methotrexate
- Pericarditis — n=6,863, PRR 30.0 Labeled adverse reaction
- Lymphoproliferative disorder — n=1,503, PRR 44.9 Labeled (related wording)
- Rheumatoid lung — n=451, PRR 37.7 Labeled (related wording)
Common questions
Which has more reported side effects, Etanercept or Methotrexate?
Etanercept has 595,118 FAERS reports and Methotrexate 483,097. More reports does not mean more dangerous: volume follows how widely and how long a drug has been used, prescription vs over-the-counter status, and publicity. The seriousness share (36% vs 73%) is a better like-for-like signal of the kind of problems reported.
Which side effects do Etanercept and Methotrexate share?
Both drugs carry disproportionality signals for duodenal ulcer perforation, bone erosion, rheumatoid nodule, granuloma skin, synovitis. Shared signals often reflect a shared drug class or the condition both are used for.
Is Etanercept or Methotrexate safer?
FAERS cannot answer that: it has no denominator and no comparator. Use this page to see which risks are already on each label and which signals are unlabeled, then check the prescribing information and your clinician for your situation.
Sources: openFDA FAERS pair statistics (OpenPV build 2026-09-14), FDA labels via openFDA, openFDA count queries for seriousness and deaths. Pair chosen because it is a commonly searched comparison. Generated 2026-10-08.