Systematic review finds more clinical harm than benefits in Alzheimer’s “treatments” lecanemab, aducanumab, and donanemab

Study ques­tions ben­e­fit of new Alzheimer’s drug (UGA Today):

Last sum­mer, the U.S. Food and Drug Admin­is­tra­tion ful­ly approved the first drug shown to slow the progress of Alzheimer’s. But new research from the Uni­ver­si­ty of Geor­gia sug­gests that patients and care­givers may not expe­ri­ence any ben­e­fit from the drug in their dai­ly lives.

The drug, Leqem­bi, became eli­gi­ble for cov­er­age through Medicare, mak­ing it more afford­able for the mil­lions of Amer­i­cans in the ear­ly stages of the dis­ease. But experts remained skep­ti­cal that the drug pro­vid­ed enough ben­e­fit to jus­ti­fy the cost and poten­tial harms of the drug.

A new study from UGA’s Mark Ebell sys­tem­at­i­cal­ly reviewed 19 pub­li­ca­tions with over 23,000 par­tic­i­pants that eval­u­at­ed eight mon­o­clon­al anti­bod­ies, includ­ing Leqembi.

“We focused very clear­ly on patient-cen­tered out­comes,” said Ebell, who is a physi­cian and pro­fes­sor of epi­demi­ol­o­gy and bio­sta­tis­tics in UGA’s Col­lege of Pub­lic Health. “We found that even after 18 to 24 months of treat­ment, the dif­fer­ences in func­tion and cog­ni­tion between treat­ed and untreat­ed patients were so small that a patient or their care­giv­er gen­er­al­ly wouldn’t notice the dif­fer­ence,” said Ebell. “For exam­ple, the Mini-Men­tal State test has 30 pos­si­ble points, but the dif­fer­ence seen in the stud­ies was less than a third of a point. To be notice­able to a patient or their fam­i­ly, that dif­fer­ence would have to be at least 1 to 3 points.”

The study sug­gests the drug’s hefty cost, time bur­den, and poten­tial side effects, which include brain swelling and brain bleeds, may not be worth the min­i­mal ben­e­fit for most patients … “The poten­tial ben­e­fit always has to be weighed against any poten­tial harms,” said Ebell. “And it’s not by any means a clear-cut choice.”

The Study:

Clin­i­cal­ly Impor­tant Ben­e­fits and Harms of Mon­o­clon­al Anti­bod­ies Tar­get­ing Amy­loid for the Treat­ment of Alzheimer Dis­ease: A Sys­tem­at­ic Review and Meta-Analy­sis (The Annals of Fam­i­ly Med­i­cine). From the Abstract:

• PURPOSE: We con­duct­ed a meta-analy­sis to eval­u­ate clin­i­cal­ly mean­ing­ful ben­e­fits and harms of mon­o­clon­al anti­bod­ies tar­get­ing amy­loid in patients with Alzheimer dementia.
• METHODS: We searched PubMed, Cochrane CENTRAL, and 5 tri­al reg­istries, as well as the ref­er­ence lists of iden­ti­fied stud­ies … Changes in cog­ni­tive and func­tion­al scales were com­pared between groups, and each dif­fer­ence was assessed to deter­mine if it met the min­i­mal clin­i­cal­ly impor­tant dif­fer­ence (MCID).
• RESULTS: We iden­ti­fied 19 pub­li­ca­tions with 23,202 total par­tic­i­pants that eval­u­at­ed 8 anti-amy­loid anti­bod­ies … None of the changes, includ­ing those for lecanemab, adu­canum­ab, and donanemab, exceed­ed the MCID. Harms includ­ed sig­nif­i­cant­ly increased risks of amy­loid-relat­ed imag­ing abnor­mal­i­ties (ARIA)-edema, ARIA-hem­or­rhage, and symp­to­matic ARIA-edema.
• CONCLUSIONS: Although mon­o­clon­al anti­bod­ies tar­get­ing amy­loid pro­vide small ben­e­fits on cog­ni­tive and func­tion­al scales in patients with Alzheimer demen­tia, these improve­ments are far below the MCID for each out­come and are accom­pa­nied by clin­i­cal­ly mean­ing­ful harms.

The Study in Context:

• Should doc­tors pre­scribe lecanemab (Leqem­bi) to women? The answer, giv­en avail­able evi­dence, is prob­a­bly No
• First, do no harm? Six rea­sons to approach anti-amy­loid drug Aduhelm cau­tious­ly, if at all
• Report: 35% of world­wide demen­tia cas­es could be pre­vent­ed by mod­i­fy­ing these 9 mod­i­fi­able risk factors