Treatment for Rheumatoid Arthritis and Risk of Alzheimer's Disease: A Nested Case-Control Analysis.
Level 4 - case-series / case-control
Nested case-control study using administrative claims data
PubMed 27470609 · doi:10.1007/s40263-016-0374-z
What was done
Researchers conducted a nested case-control study using the Verisk Health claims database encompassing over 8.5 million commercially insured US adults aged 18 and older from all 50 US states, Puerto Rico, and the US Virgin Islands. They identified subjects with rheumatoid arthritis (RA) alone (controls) and subjects with both RA and Alzheimer's disease (AD) (cases), matching them on age, sex, exposure assessment period, and methotrexate treatment. They evaluated the association between AD risk and exposure to RA therapies (including the anti-TNF agents infliximab, adalimumab, and etanercept, as well as methotrexate, prednisone, sulfasalazine, and rituximab), adjusting odds ratios for comorbidities including coronary artery disease, diabetes mellitus, and peripheral vascular disease.
What was found
AD prevalence was significantly higher among RA patients (0.79%) than among non-RA patients (0.11%, p < 0.0001). Among RA patients, AD risk was significantly increased by diabetes (adjusted OR 1.86; 95% CI 1.32–2.62; p = 0.0004), peripheral vascular disease (adjusted OR 1.61; 95% CI 1.06–2.43; p = 0.02), and coronary artery disease (adjusted OR 1.48; 95% CI 1.04–2.05; p = 0.03). Exposure to anti-TNF agents as a class was associated with reduced AD risk (adjusted OR 0.45; 95% CI 0.23–0.90; p = 0.02). In subgroup analyses of individual anti-TNF agents, only etanercept showed a statistically significant reduction in AD risk (unadjusted OR 0.33; 95% CI 0.08–0.94; p = 0.03; adjusted OR 0.30; 95% CI 0.08–0.89; p = 0.02), whereas other studied immunosuppressive drugs did not.
Why it matters
This study provides real-world observational evidence that systemic anti-inflammatory treatment targeting TNF-alpha, particularly etanercept, is associated with a lower incidence of Alzheimer's disease in patients with rheumatoid arthritis.
Limits
The abstract does not report the exact sample size (n) for the matched cases and controls. Because this is a retrospective claims-based study, it is susceptible to residual confounding by indication, coding errors, and unmeasured lifestyle factors, and the etanercept subgroup estimate has very wide confidence intervals.
Cited by
- supports Individuals taking TNF-alpha inhibitor drugs have approximately a 50% lower risk of developing Alzheimer's disease.