By Lucy Piper, medwireNews reporter
medwireNews: Clinical evidence to date is not sufficient to be able to demonstrate a benefit from extending treatment with lecanemab beyond 18 months, so without really knowing should we be discontinuing treatment in those who currently receive it?
This was the predicament revealed in a debate between Dorota Religa (Karolinska Institutet, Stockholm, Sweden) and Lon Schneider (Keck School of Medicine of University of Southern California, Los Angeles, USA) at the 18th World Congress on Controversies in Neurology in London, UK.
Dorota Religa (Karolinska Institutet, Stockholm, Sweden) presented the case for why lecanemab treatment should be continued beyond 18 months, her basis for which was that “currently, there are no data on treatment beyond 18 months.”
This means that the decision on whether, how, and when to discontinue anti-amyloid treatment in a patient for whom the drug is effective and tolerated is based on clinical judgement, and there is very little evidence to support this decision, Religa pointed out.
For instance, “we do not know what happens when you stop therapy,” she explained. Also, treatment appears to be better tolerated over time, with side effects mainly occurring at the beginning.
She believes that it would be good to continue treatment beyond 18 months in some patients in the clinic and compare them with patients who do not continue treatment to see the effects on disease progression, so that we can “gather more data and have the answer.”
Indeed, this offers the “great opportunity” for a real-world registry, she highlighted. A patient could participate in a prospective trial and report into a registry, assuming that the appropriate clinical team and resources for follow-up are available.
Opposing the argument that lecanemab treatment should be continued beyond 18 months, was Lon Schneider (Keck School of Medicine of University of Southern California, Los Angeles, USA).
He agrees that supporting data are largely absent, given that only about 1000 patients have been treated beyond 18 months and very few regular patients in the USA have been exposed to lecanemab for more than 9 months.
Commenting on his own experience of prescribing lecanemab at USC, Schneider said that they review positron emission tomography scans before starting lecanemab treatment and at 18 months. At this point, they would expect “70–80% of compliant patients to be amyloid negative,” with levels below 25 centiloids, and would stop treatment.
He questioned some of the statistical and methodological modelling currently used to show clinical meaningfulness of lecanemab beyond the 18-month trial, based on projection, which he said may be misleading.
He explained that the backward projection to placebo modelling that has been used projects the decline with lecanemab after 18 months to be equivalent to that with placebo at 12.7 months, a time saving of about 5.3 months. However, Schneider pointed out that this does not account for absolute differences between treatment arms, which may differ depending on whether the placebo decline decreases or increases, for instance.
He added that this modelling is also based on assumptions, such as a slowing in placebo decline, that there are no missing data or data missing completely at random, and that the decline rates for both arms are the same during the period of comparison.
Essentially, projecting backwards is making comparisons of non-comparable groups because there will be people who dropout and stop treatment, he explained.
Schneider concluded that evidence of clinical meaningfulness depends on being able to show a difference in Clinical Dementia Scale Sum of Boxes scores between lecanemab and placebo and mathematical transformation of this is not clinically meaningful.
Other studies looking at the longer-term effects of anti-amyloids versus placebo in patients with pre-clinical disease are underway and Schneider expects that we may have more answers on this by about 2028.
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2024 Springer Healthcare Ltd, part of the Springer Nature Group
CONy 2024; London, UK: March 21–23
