In the Journals

Placebo effect common in uncontrolled asthma trials

In five randomized controlled trials, patients with persistent, uncontrolled asthma who received placebo therapy demonstrated statistically significant improvement in outcomes, according to a study published in the Annals of the American Thoracic Society.

“Although the symptoms associated with asthma are subjective by nature, one of the hallmarks of asthma is that changes in baseline lung function and changes in airway inflammation can occur rapidly with medical intervention and these changes can be objectively quantified. As such, asthma can be an excellent disease model to study placebo effects,” the researchers wrote. “Our objective was to determine whether the magnitudes of placebo effects vary between different clinical outcomes or vary depending on characteristics of the study population, and to determine how statistical methods can be used to isolate explanatory factors for these effects.”

Across five clinical trials — AMAZES, MENSA, MUSCA, LAVOLTA I and LAVOLTA II — all clinical outcomes were significantly improved in patients with uncontrolled asthma randomly assigned placebo.

The magnitude of placebo effects was greatest for health care utilization outcomes, including a median 31% reduction in risk for exacerbations, a median 50% reduction in risk for ED visits and a median 66% reduction in risk for hospitalizations for asthma. For patient-reported outcomes, the placebo effect was considered intermediate, with a median 25% improvement in Asthma Control Questionnaire scores and a median 19.5% improvement in St. George’s Respiratory Questionnaire scores.

The smallest relative placebo effects were noted for objective study outcomes measured the day of randomization and at the study’s conclusion, with only a median 4.2% improvement in forced expiratory volume in 1 second (FEV1).

No subgroup appeared to be more susceptible to placebo effects, according to subgroup analyses.

The researchers also examined the results from goodness-to-fit tests of the negative binomial models for AMAZES, MENSA and MUSCA. Exacerbations during the study period fit the model for all three studies and exacerbations in the prestudy period for AMAZES also showed a good fit. For MENSA and MUSCA, exacerbations experienced in the prestudy period showed a significant departure from the negative binomial distribution test, with an unusually large number of patients in MUSCA reporting exactly two exacerbations during the prestudy year.

“Contributing factors to placebo effects could include: (1) neurobiological mechanisms mediating placebo effects, (2) psychological factors arising from expectations of benefit, (3) better-than-usual clinical monitoring and patient care by the study team during the trial period, (4) better subject adherence to baseline asthma medications and therapies while on the study, and (5) beneficial self-prompted changes in lifestyle by subjects not explicitly prescribed in the study protocol,” the researchers wrote. – by Melissa Foster

Disclosure: Healio Pulmonology could not confirm relevant financial disclosures at the time of publication.

In five randomized controlled trials, patients with persistent, uncontrolled asthma who received placebo therapy demonstrated statistically significant improvement in outcomes, according to a study published in the Annals of the American Thoracic Society.

“Although the symptoms associated with asthma are subjective by nature, one of the hallmarks of asthma is that changes in baseline lung function and changes in airway inflammation can occur rapidly with medical intervention and these changes can be objectively quantified. As such, asthma can be an excellent disease model to study placebo effects,” the researchers wrote. “Our objective was to determine whether the magnitudes of placebo effects vary between different clinical outcomes or vary depending on characteristics of the study population, and to determine how statistical methods can be used to isolate explanatory factors for these effects.”

Across five clinical trials — AMAZES, MENSA, MUSCA, LAVOLTA I and LAVOLTA II — all clinical outcomes were significantly improved in patients with uncontrolled asthma randomly assigned placebo.

The magnitude of placebo effects was greatest for health care utilization outcomes, including a median 31% reduction in risk for exacerbations, a median 50% reduction in risk for ED visits and a median 66% reduction in risk for hospitalizations for asthma. For patient-reported outcomes, the placebo effect was considered intermediate, with a median 25% improvement in Asthma Control Questionnaire scores and a median 19.5% improvement in St. George’s Respiratory Questionnaire scores.

The smallest relative placebo effects were noted for objective study outcomes measured the day of randomization and at the study’s conclusion, with only a median 4.2% improvement in forced expiratory volume in 1 second (FEV1).

No subgroup appeared to be more susceptible to placebo effects, according to subgroup analyses.

The researchers also examined the results from goodness-to-fit tests of the negative binomial models for AMAZES, MENSA and MUSCA. Exacerbations during the study period fit the model for all three studies and exacerbations in the prestudy period for AMAZES also showed a good fit. For MENSA and MUSCA, exacerbations experienced in the prestudy period showed a significant departure from the negative binomial distribution test, with an unusually large number of patients in MUSCA reporting exactly two exacerbations during the prestudy year.

“Contributing factors to placebo effects could include: (1) neurobiological mechanisms mediating placebo effects, (2) psychological factors arising from expectations of benefit, (3) better-than-usual clinical monitoring and patient care by the study team during the trial period, (4) better subject adherence to baseline asthma medications and therapies while on the study, and (5) beneficial self-prompted changes in lifestyle by subjects not explicitly prescribed in the study protocol,” the researchers wrote. – by Melissa Foster

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Disclosure: Healio Pulmonology could not confirm relevant financial disclosures at the time of publication.