Placebo response and its influencing factors in acne vulgaris: A model-based meta-analysis.

AIMS: The high placebo response in acne clinical trials has slowed down the progress of new drug development. Therefore, this study used a model-based meta-analysis method to quantitatively analyse the placebo response and explore its influencing factors.

METHODS

This study included 21 627 subjects from acne-related randomized double-blind placebo-controlled trials. Pharmacodynamic models were developed for four endpoints: total lesion counts absolute change, noninflammatory lesion counts absolute change, inflammatory lesion counts absolute change and treatment success rate defined by the investigator global assessment scale. Covariate modelling and subgroup analyses were performed to explore influencing factors. Placebo response under different conditions was simulated based on the final model.

RESULTS

Model simulation results showed that for the typical population, after 12 weeks of placebo intervention, their total lesion counts, noninflammatory lesion counts and inflammatory lesion counts were reduced by 19.05 (95% confidence interval: 16.54-21.52), 10.71 (9.18-12.17) and 8.58 (7.55-9.58) from baseline, respectively; the treatment success rate was 11.83% (9.41%-14.35%). Baseline lesion counts, female proportion, Caucasians proportion, sample size, dosage form, type of control drug, skincare programme, number of centres, funding source, study locations and publication year could all influence placebo response. We also used our model to synthesize placebo arms for two single-arm studies, demonstrating the efficacy superiority of the drugs.

CONCLUSIONS

This study quantitatively described the time-response relationship of placebo in acne clinical trials, revealing the influence of baseline characteristics and trial design characteristics, which could provide evidence for optimizing clinical trial design.

TRIAL REGISTRATION: PROSPERO (CRD420250649902).