Abstract Details

Title The lessebo effect in Parkinson's disease: insights from individual patient data meta-analyses

Topic Movement Disorders

Presentation(s) S41 - Parkinson's Disease Interventions and Clinical Trials (2:48 PM-3:00 PM)

Poster/Presentation
Number 010

Objective To evaluate the outcome specificity and temporal evolution of the lessebo effect in Parkinson's disease (PD).

Background The inclusion of a placebo arm in a randomized double-blind controlled trial may be associated with the reduction of the observed efficacy of a therapeutic intervention. This phenomenon is called lessebo effect. Little is known about the lessebo effect in PD.

Design/Methods We performed one-stage individual patient data meta-analyses of randomized controlled trials conducted in PD to 1) assess a symptomatic motor effect at any PD clinical stage, 2) to determine a disease-modifying effect in early PD. We accessed clinical trials available in the PSG (CALM-PD, TEMPO) and the NINDS PD-DOC project (ELLDOPA, FS1, FSTOO, QE2, DATATOP, PRECEPT). After data harmonization into a common dataset exclusively with active treatment arms, we evaluated the association between the probability of placebo allocation and change in efficacy outcome measures (1. motor UPDRS, UPDRS part II, 2. time to start of dopaminergic treatment). We used 1) mixed modelling with repeated measures and 2) a Cox proportional hazards model, respectively, controlling for relevant confounders. A P value<0.05 was deemed significant.

Results

In PD trials conducted to assess a symptomatic motor benefit (n=815), the adjusted between-group difference in the motor UPDRS was 6.0 units (95% CI: 5.1 - 7.0), and 1.8 units (95% CI: 1.4 - 2.3) in the UPDRS part II at weeks 24-26 of treatment, in favor of active-controlled trials. Consistent results were observed at weeks 3-4 and 9-14.

In disease-modifying trials (n=1165), the adjusted hazard ratio of the time to onset of dopaminergic therapy was 1.15 (95% CI: 0.92 - 1.43) comparing a probability of placebo allocation of 0.25 vs. 0.33.

Conclusions In PD, the lessebo effect is measurable, clinically significant and persistent up to 6 months in symptomatic trials for motor symptoms. Its presence in disease-modifying trials requires further evaluation.

Authors/Disclosures
Tiago Mestre, MD, MSC (University of Ottawa) PRESENTER	Dr. Mestre has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CHDI. Dr. Mestre has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for PTC. Dr. Mestre has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abbvie. Dr. Mestre has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ipsen. Dr. Mestre has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abbvie. Dr. Mestre has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Abbvie. The institution of Dr. Mestre has received research support from CIHR. The institution of Dr. Mestre has received research support from Ontario Research Fund. The institution of Dr. Mestre has received research support from MJFF. The institution of Dr. Mestre has received research support from Parkinson Canada. The institution of Dr. Mestre has received research support from University of Ottawa/PRC.
	No disclosure on file
	No disclosure on file
Joaquim Ferreira (Instituto De Medecina Molecular Lisboa)	No disclosure on file
Anthony E. Lang, MD, FAAN (Toronto Western Hospital)	Dr. Lang has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for AbbVie, Amylyx, Aprinoia, Biogen, BioAdvance, Biohaven, BioVie, BlueRock, BMS, Denali, Janssen, Lilly, Pharma 2B, Sun Pharma, and UCB. Dr. Lang has received personal compensation in the range of $50,000-$99,999 for serving as an Expert Witness for medicolegal cases related to paraquat. The institution of Dr. Lang has received research support from AbbVie. Dr. Lang has received intellectual property interests from a discovery or technology relating to health care. Dr. Lang has received publishing royalties from a publication relating to health care.

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