Abstract
Patients with multiple sclerosis (MS)
taking natalizumab are at risk for progressive multifocal
leukoencephalopathy (PML). We sought to describe the outcomes of
discontinuing natalizumab on the basis of PML risk and those of
obtaining additional screening across a range of scenarios using
decision tree models.
Methods
Health state probabilities and values,
measured as the proportion of quality–adjusted life years (PQALY)
relative to baseline health, were based on literature review.
Probabilities of worsening MS while continuing and discontinuing
natalizumab were set to 0.23 and 0.44. For discontinuing therapy, PML
risk, worsening MS value, and PML value were varied. For additional
screening, the probability of discontinuing natalizumab without
screening, PML risk, worsening MS value, and PML value were set to 33%,
1.1%, 0.88, and 0.09, respectively, with test sensitivity and
specificity varying from 0.50 to 1.
Results
Discontinuing natalizumab provided no
benefit until PML risk reached 2.9%, assuming an MS relapse value of
0.88 and a PML value of 0.09. Additional screening changed the PQALY by
−0.3% to 1.5%, largely influenced by specificity. Assuming a sensitivity
of 80% and a specificity of 99%, screening increases the PQALY by 1.2%.
Conclusions
The highest PML risk identified by
stratification is below 2.9%, suggesting that continuing natalizumab
outweighs PML risk for most patients on the basis of theoretical
calculations. However, decisions based on additional screening with
high-specificity tests, including polymerase chain reaction
cerebrospinal fluid tests for John Cunningham virus, may provide benefit
and should be clinically tested. Increased precision of probabilities
and quality-of-life values are also needed to improve decision making.
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