Long-term effectiveness and cost-effectiveness of testing for alemtuzumab antidrug antibodies to guide treatment in multiple sclerosis: a modelling study

Biologic therapies are increasingly used in multiple sclerosis (MS), but often provoke anti-drug antibodies, potentially leading to treatment failure. Testing for anti-drug antibodies to guide treatment switching could improve clinical- and cost- effectiveness of MS treatment. We assess the value of testing for anti-drug antibodies to alemtuzumab, an effective but immunogenic MS therapy. We developed a microsimulation model to project disease progression, quality of life, and cost outcomes in people with relapsing-remitting MS initiating alemtuzumab treatment without and with alemtuzumab anti-body testing. Risk of anti-drug antibody development was informed by a UK cohort study of alemtuzumab-treated people with MS. UK guidance informed MS treatment strategies. Alemtuzumab anti-drug antibody test-directed treatment switching resulted in 0.02 fewer MS relapses per person; prolonged time to secondary progressive disease by 0.06 years; and yielded 0.02 additional years of life (0.06 Quality-Adjusted Life Years (QALY)). At £25/test, incremental cost per QALY gained was £47,861, with the additional cost arising from increased time on disease-modifying therapies (DMTs). Cost-effectiveness of anti-drug antibody testing was sensitive to anti-drug antibody development risk, their impact on drug efficacy, and costs of disease-modifying therapies (DMTs). Anti-drug antibody testing to inform MS treatment switching could improve clinical outcomes, but its cost-effectiveness depends on anti-drug antibody risk, its impact on drug efficacy, and costs of DMTs.