This post was created by Dr Tim Jamieson, a Health Economist at the Wolfson Institute of Population Health, Queen Mary University of London about his recent publication in the European Journal of Health Economics.
The Health Economic and Policy Research Unit at QMUL has just published a piece of work in conjunction with Dr Sharmilee Gnanapavan examining the cost-effectiveness of anti-drug antibody (ADA) testing to guide treatment decisions in people with MS treated with alemtuzumab.
In this study they modelled the impact of treatment failure caused by anti-drug antibodies in people receiving alemtuzumab, looking at how this affected the long-term course of MS and the overall cost-effectiveness of treatment. Alemtuzumab is a ‘biological therapy’, a large, complex, protein similar to substances naturally found in the body. Biological therapies make up an increasing number of MS treatments, and many are among the most effective options available. However their size and similarity to natural proteins mean they can be recognised by the immune system as foreign, triggering an immune response that includes the formation of antibodies against the drug. These antibodies can attach to the drug and may reduce its effectiveness. When this happens people may experience relapses or disability progression that might not have occurred had they been treated with a different drug. Biological therapies are also high-cost (typically around £20,000 per year), so continuing a treatment that is no longer effective has significant implications for both individuals health but also cost to the NHS.
Alemtuzumab was chosen for this study because it appears to provoke a particularly strong immune response compared with other biological therapies. People on alemtuzumab have two short treatment courses over two years, and then only receive further treatment, as a single third cycle, if they experience a relapse. Using real patient profiles and the NHS England treatment pathway, they developed a computer model of MS allowing two approaches to be compared: the standard pathway without ADA testing, where a third cycle is given if a relapse occurs, and a pathway where ADA results taken after the second cycle could be used to instead guide a switch to another disease-modifying therapy if MS activity later returned, and they had developed these anti-drug antibodies. The model followed each simulated person over their lifetime, tracking relapses, changes in disability level, treatment switches, and associated NHS costs.
The results suggested that using ADA testing to guide treatment decisions could provide modest clinical benefits – slightly fewer relapses, a longer time before transitioning to secondary progressive MS, and slower disability progression. Perhaps counterintuitively though overall costs were higher. This is because better clinical outcomes meant people remained eligible for disease-modifying therapies for longer under current guidelines – these additional costs therefore reflect the extra time spent on other treatments after switching, which have substantial ongoing annual costs.
The modelling was based on some strong assumptions – that anti-drug antibodies completely blocked effectiveness, and that the anti-drug antibody test was completely accurate. Models varying these assumptions demonstrated the importance particularly of two things, false positive rates, and the impact of ADAs on alemtuzumab effectiveness. Because alemtuzumab is one of the most effective MS drugs a false positive will results in a switch being made to most likely a less effective drug, and similarly if ADAs only partially block effectiveness then it may still be more effective than other treatments. As shown in the figure below at about 75% effectiveness remaining, testing becomes harmful, both from a disease and cost perspective. Of course, the other key driver of cost-effectiveness was found to be the cost of the drugs themselves.
Although the study focused on alemtuzumab, the framework developed can be applied to any biological therapy in MS, and indeed to biologics used in other disease areas. Further work is needed to define the performance of ADA tests, particularly how accurately they detect antibodies, and how often they produce false positive results. Probably more importantly, more evidence is required on how much ADAs reduce the effectiveness of alemtuzumab and other biological therapies, in MS and across all the disease areas they are applied in.
Abstract
Eur J Health Econ. 2025 Nov 12.
Long-term effectiveness and cost-effectiveness of testing for alemtuzumab antidrug antibodies to guide treatment in multiple sclerosis: a modelling study
Timothy Jamieson , Florian Tomini , Sharmilee Gnanapavan , Borislava Mihaylova
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.
Source: multiple-sclerosis-research.org