{"doi":"10.1002/ana.26344","title":"Reply to A Letter Concerning “Aducanumab: What About the Patient?”","abstract":"I read the letter submitted by Gandy commenting on my editorial, Aducanumab: What About the Patient? with great interest.1, 2 Gandy takes issue with the role of incorporating the patient into the decision-making process regarding involvement in therapies with monoclonal anti-Aβ antibodies such as aducanumab. He contends the data supporting its clinical use are lacking. It is true that the clinical data supporting the accelerated approval by the U.S. Food and Drug Administration (FDA) for aducanumab have only recently published.3 Accelerated approval means that there was evidence of the biological impact of the therapy, but without clinical efficacy data. This is the essence of the situation to be presented to the patient. Gandy contends that data such as those reported by Ackley et al. on a meta-analysis of previous anti-amyloid therapies should be presented to the patient.4 These data need to be interpreted very carefully. The primary concern with the paper by Ackley et al. is their statement that this class of agents provided no clinical benefit, a conclusion reached after combining old data on earlier incarnations of anti-Aβ therapies, some targeting monomers, and some targeting secretase inhibitors. There were numerous issues with these previous studies, such as participants in some studies not having the drug target present, multiple mechanisms of action, and little evidence of target engagement, all of which made this meta-analysis difficult to interpret.5-8 Their reasoning is analogous to concluding that antibiotics, as a class, are ineffective because one or more drugs lack sensitivity to a particular pathogen. The meta-analysis by Ackley et al. overlooks more recent trials that have suggested a clinical benefit when the drug target, amyloid plaque level, one of the defining features of the disease, has been reduced.9-11 These data present a much different picture from those presented in the meta-analysis. Consequently, when Gandy and colleagues present data to their patients, there is no doubt that they offer an incomplete picture of the data. Perhaps a more balanced approach, such as that recommended by the recent appropriate use recommendations for monoclonal antibodies, would be more appropriate.12 It is heartening to see that Gandy is still pursuing the role of the toxicity of amyloid Aβ oligomers and Aβ fibrils in impacting synaptic integrity. There is strong evidence that this approach may be beneficial, and these data are not inconsistent with the current approaches involving anti-Aβ therapies. In summary, I still maintain that the role of the patient is critical with respect to the decision of whether to pursue treatment with a monoclonal antibody against Aβ. Indeed, it is the most important role; it has been a long-established precept of our discipline that “the best interest of the patient is the only interest to be considered,”13 and certainly, sharing all available data is imperative to that interest. However, selecting the appropriate method of presenting the data is critical to allow the patient to make an informed and, as much as possible, unbiased decision.","journal":"Annals of Neurology","year":2022,"id":306549,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.955,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":27599,"name":"Ronald C. Petersen","orcid":"0000-0002-8178-6601","position":0,"is_corresponding":true}],"reference_count":15,"raw_metadata":null,"created_at":"2026-07-19T00:32:48.984902Z","pmid":"35249233","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}