Jamieson T, Tomini F, Gnanapavan S, Mihaylova B. Long-term effectiveness and cost-effectiveness of testing for alemtuzumab antidrug antibodies to guide treatment in multiple sclerosis: a modelling study. Eur J Health Econ. 2025 Nov 12. doi: 10.1007/s10198-025-01854-8
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.
NDG has a person treated with MS who was doing badly and wanted the blood to tested for the presence of anti-drug antibodies (ADA) and it was not an easy request to get an answer. Pharma not only control the trial data but often control the ADA assays. It is often inferred that the influence of ADA is minimal….This is largely the cases from a population consideration but if you are the person with the ADA then they can be really important.
Prof. A has designed a way to rapidly develop tests for ADA to any antibody drug. The people for Cardiff supplied us with blood samples to test and this is what happened in one individual. The graph shows the time of dosing and you can see the individual had 6 doses and at about £21,000-£22,000 a dose you can see the basic drug costs are alot. Prof A did the testing and as you can see it was evident before dose three that there was a marked ADA response and he found that if the units of an ADA response was over 15,000 the drug was not going to work and it would not effectively deplete white blood cells. You can see they drop after the first two doses but not for the third, forth, fifth or sixth dose so that is arounf £85,000 of wasted money giving a drug that was never going to work…Even without the ability to test ADA, a simple blood test before and after alemtuzumab shows if the drug is working and depleting or not.
No only was £85,000 and the rest wasted (I suspect they were part of the trial so the neuros were blinded to the the white cell counts they were signed up to a protocol that was to retreat if there was disease breakthrough not to stock and change to something else…but in the process the individual when from fully ambulatory to requiring 1-2 sticks to walk (EDSS 3 to EDSS 6-6.5) that is two thirds along the path from health to death. The costs to the individual and the NHS are alot more that the cost of a well-placed antibody test and a blood count.
For a depleting antibody to work, they have to be seen to be deplete so if you are taking a depleting antibody just remember this. Likewise ProfA and team have reported at ECTRIMS2025 that migration inhibitors can increase the number of circulating white blood cells, if they do not then maybe ADA are stoping the drug from working…More on this soon
Source: multiple-sclerosis-research.org