IVIg treatment associated with a reduced risk of Alzheimer's disease

In a retrospective analysis published in the journal Neurology, investigators demonstrated that previous treatment with intravenous immunoglobulin (IVIg) was associated with a reduced risk of the development of Alzheimer's disease and related disorders (ADRD) in patients aged ≥65 years.

In this retrospective, case-control analysis, investigators assessed claims data from a national database of physician claims (containing data from approximately 270,000 providers and approximately 20 million patients aged ≥65 y) for patients aged ≥65 years who had service dates from April 1, 2002, to August 31, 2007. Patients designated as study cases had received ≥1 IVIg administration with an average dose per administration ≤90,000 mL between April 1, 2001, and August 31, 2004. None of the case patients had received intramuscular (IM) or subcutaneous (SC) Ig treatment. Case patients were also required to have ≥1 claim from ≥1 year before the first IVIg administration to confirm the absence of a diagnosis of ADRD at the time of IVIg treatment. Diagnoses of ADRD included diagnoses of senile dementia, presenile dementia, other specified senile psychotic conditions, unspecified senile psychotic condition, AD, Pick disease, other frontal temporal dementia, senile degeneration of the brain, and senility without mention of psychoses. Additionally, case patients were required to have ≥1 medical claim in each of the 3 consecutive years after the initial IVIg treatment to establish that their file was active within the claims database for ≥731 days of follow-up after the index date. Patients who were diagnosed with ADRD exited the study on the date of diagnosis. Control patients were those who had a medical claim between April 1, 2000, and August 31, 2003; were not treated with IVIg; and had no diagnosis of ADRD in the year before the index date. Control and case patients were matched 100:1 on the basis of age, sex, and risk factors for ADRD (including hypertension, hypercholesterolemia, diabetes, and chronic kidney disease).

The analysis included a total of 847 case patients and 84,700 control patients. Case patients had received a mean of 14 IVIg treatments. Among case patients, 2% were diagnosed with ADRD in the postindex period versus 4.1% of control patients (P=.002). The proportion of IVIg-treated patients diagnosed with ADRD was lower than the proportion of control patients diagnosed with ADRD in all 3 age groups examined (patients aged 65–74 y, 0.6% vs 2.2%; P=.021; aged 75–84 y, 3.7% vs 6.2%; P=.062; aged >84 y, 5% vs 12%; P=.177). A Cox proportional hazards model demonstrated that treatment with IVIg was associated with a 42% lower risk of diagnosis of ADRD compared with no treatment (HR=0.577; 95% CI, 0.359–0.93; P=.024). The statistical model predicted that after 5 years' observation, 2.8% of IVIg-treated patients and 4.8% of control patients would be diagnosed with ADRD. Sensitivity analyses that took into account differences in length of follow-up and diagnosis codes demonstrated results similar to those described above.

The investigators suggested that future studies should examine the potential relationship between cumulative IVIg dose and the risk of development of ADRD. They pointed out that although further studies are needed, their analysis "provides epidemiologic evidence that previous IVIg may have a protective effect on the development of ADRD."

SOURCE

Fillit H, Hess G, Hill J, Bonnet P, Toso C. IV immunoglobulin is associated with a reduced risk of Alzheimer disease and related disorders. Neurology. 2009;73:180–185.