Previously reported placebo-response-associated variants do not predict patient outcomes in inflammatory disease Phase III trial placebo arms

• Published in: Genes and immunity Vol. 20; no. 2; pp. 172 - 179
• Main Authors: Haug-Baltzell, Asher, Bhangale, Tushar R, Chang, Diana, Dressen, Amy, Yaspan, Brian L, Ortmann, Ward, Brauer, Matthew J, Hunkapiller, Julie, Reeder, Jens, Mukhyala, Kiran, Cuenco, Karen T, Tom, Jennifer A, Cowgill, Amy, Vogel, Jan, Forrest, William F, Behrens, Timothy W, Graham, Robert R, Wuster, Arthur
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.02.2019; Nature Publishing Group UK
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - genetics; Asthma; Asthma - drug therapy; Asthma - genetics; Brief Communication; Clinical outcomes; Clinical trials; Clinical Trials, Phase III as Topic - standards; Data processing; Female; Genome-Wide Association Study; Genomes; Humans; Inflammatory diseases; Male; Middle Aged; Patients; Placebo Effect; Polymorphism, Single Nucleotide; Rheumatoid arthritis; Statistical analysis
• ISSN: 1466-4879; 1476-5470
• DOI: 10.1038/s41435-018-0018-z

In clinical trials, a placebo response refers to improvement in disease symptoms arising from the psychological effect of receiving a treatment rather than the actual treatment under investigation. Previous research has reported genomic variation associated with the likelihood of observing a placebo response, but these studies have been limited in scope and have not been validated. Here, we analyzed whole-genome sequencing data from 784 patients undergoing placebo treatment in Phase III Asthma or Rheumatoid Arthritis trials to assess the impact of previously reported variation on patient outcomes in the placebo arms and to identify novel variants associated with the placebo response. Contrary to expectations based on previous reports, we did not observe any statistically significant associations between genomic variants and placebo treatment outcome. Our findings suggest that the biological origin of the placebo response is complex and likely to be variable between disease areas.