Question explored with the scientific record
Conversation so far
- 1 Is an immunosuppressant shot worth it for a AS?
- 2 Which AS symptoms did trials improve most, pain or stiffness or function?
- 3 What are the most common serious risks of TNF blockers vs NSAIDs?
Answered on this page ↓
What are the most common serious risks of TNF blockers vs NSAIDs?
The short version: TNF blockers carry a real, measurable risk of serious infection; NSAIDs carry a real, measurable risk of GI bleeding and cardiovascular events. Neither is "safe," and the two harms are not the same kind.
TNF blockers' signature serious risk is infection. In a Japanese registry, TNF-inhibitor patients had serious infections at 6.42 per 100 patient-years versus 2.64 on conventional drugs, roughly 2.4 times the rate [1]. A US review found serious adverse events at 6.4 per 100 patient-years on etanercept and 6.2 on infliximab versus 2.3 on conventional treatment [3]. The atypical infections are the distinctive ones: TB, histoplasmosis, listeriosis, and other fungal infections, with infliximab carrying far more reported cases than etanercept [2].
NSAIDs' signature serious risk is gastrointestinal bleeding. Current NSAID use carried a relative risk of 2.6 for GI bleeding in one case-control study [4], 4.4 for hospitalization for upper GI bleeding in another [5], and 4.7 in a large UK study [7]. Cardiovascular risk is the other half: higher-dose ibuprofen produced 7 to 9 non-fatal and 2 fatal cardiovascular events per 1000 patients per year [6], and NSAID use after a first heart attack raised one-year mortality risk by about 59% [8].
| Harm | Drug class | Figure |
|---|---|---|
| Serious infection | TNF blockers | 6.42 vs 2.64 per 100 patient-years [1] |
| Serious adverse events | TNF blockers | 6.4 vs 2.3 per 100 patient-years [3] |
| GI bleeding | NSAIDs | RR 2.6 [4] |
| Upper GI bleed hospitalization | NSAIDs | RR 4.4 [5] |
| CV events, higher-dose ibuprofen | NSAIDs | 7-9 non-fatal, 2 fatal per 1000/year [6] |
These are different populations and different study designs, so the numbers are not a clean head-to-head. The retrieval did not surface a trial randomizing AS patients to TNF blocker versus NSAID and counting serious harms in both arms. That comparison is what would settle it.
My call: for a person with AS, TNF blockers trade a modest infection risk for symptom control; NSAIDs trade GI and cardiovascular risk. Which is worse depends on your age, gut history, and heart risk. Confidence: moderate.
Sources used 8
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Incidence and Risk Factors for Serious Infection in Patients with Rheumatoid Arthritis Treated with Tumor Necrosis Factor Inhibitors: A Report from the Registry of Japanese Rheumatoid Arthritis Patients for Longterm Safety
This study investigates the incidence and risk factors for serious infections in Japanese patients with rheumatoid arthritis treated with tumor necrosis factor inhibitors compared to those receiving nonbiological disease-modifying antirheumatic drugs, revealing a significantly i…
DOI: 10.3899/jrheum.101009 -
Serious Infections Associated with Anticytokine Therapies in the Rheumatic Diseases
This is a comprehensive review of the spectrum and mechanisms of serious infections associated with tumor necrosis factor (TNF) inhibitors and other anticytokine therapies in inflammatory diseases, summarizing clinical trial and postmarketing data (notably TB, histoplasmosis, li…
DOI: 10.1177/0885066604267854 -
Infections in patients with rheumatoid arthritis treated with biologic agents
This study estimates the incidence rates of serious and nonserious infections in patients with rheumatoid arthritis treated with biologic agents compared to those receiving conventional treatment, revealing a higher risk associated with TNF inhibitors.
DOI: 10.1002/art.21386 -
Risk of Upper and Lower Gastrointestinal Bleeding in Patients Taking Nonsteroidal Anti-inflammatory Drugs, Antiplatelet Agents, or Anticoagulants
This study quantifies the relative risk of upper and lower gastrointestinal bleeding associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs), antiplatelet agents (APAs), and anticoagulants, finding that anticoagulants pose the highest risk for both types of blee…
DOI: 10.1016/j.cgh.2014.11.007 -
Risk of Hospitalization for Upper Gastrointestinal Tract Bleeding Associated With Ketorolac, Other Nonsteroidal Anti-inflammatory Drugs, Calcium Antagonists, and Other Antihypertensive Drugs
This study investigates the risk of hospitalization for upper gastrointestinal tract bleeding associated with the use of ketorolac and other NSAIDs, revealing that ketorolac presents a significantly higher risk compared to other medications.
DOI: 10.1001/archinte.158.1.33 -
The dangers of NSAIDs: look both ways
This study highlights the significant risks associated with non-steroidal anti-inflammatory drugs (NSAIDs) in older populations, emphasizing the need for safer prescribing practices to mitigate preventable adverse drug reactions (ADRs).
DOI: 10.3399/bjgp16X684433 -
Risk of upper gastrointestinal bleeding and perforation associated with Individual non-steroidal anti-inflammatory drugs
A population-based retrospective UK case-control study showing that current use of individual NSAIDs markedly increases the risk of upper gastrointestinal bleeding (UGIB), with a strong dose- and duration-related effect, notable drug-specific differences (highest with azapropazo…
DOI: 10.1016/s0140-6736(94)91843-0 -
Long-Term Cardiovascular Risk of Nonsteroidal Anti-Inflammatory Drug Use According to Time Passed After First-Time Myocardial Infarction
This nationwide cohort study investigates the long-term cardiovascular risks associated with nonsteroidal anti-inflammatory drug (NSAID) use following a first-time myocardial infarction, revealing that NSAID use is linked to increased mortality and coronary events regardless of …
DOI: 10.1161/CIRCULATIONAHA.112.112607