Abstract
Background
Relative changes in Psoriasis Area and Severity Index (PASI) are used as outcomes in psoriasis clinical trials but are limited when analysing long-term data and in routine practice. Absolute PASI may be more clinically useful.
Objectives
To develop and implement a methodology for assessing the probability of achieving and maintaining a “response” in patients with psoriasis, defined using absolute PASI.
Materials & Methods
This analysis included pooled data from the Phase III AMAGINE-2 and -3 trials. Absolute PASI was described using all available data. Multistate modelling was used to compare the probabilities of achieving (absolute PASI = 0) and maintaining (absolute PASI ≤2) a response, and the time in the response state, in patients receiving brodalumab vs ustekinumab.
Results
Higher proportions of patients achieved lower absolute PASI over 52 weeks with brodalumab vs ustekinumab. The probability of achieving the response state was greater with brodalumab vs ustekinumab over 52 weeks (hazard ratio: 1.96; 95% confidence interval [CI]: 1.66–2.31, p < 0.001). At Week 52, there was a higher probability of being in response with brodalumab vs ustekinumab (81% [95% CI: 74–89%] vs 60% [95% CI: 54–67%], respectively). Mean time in response was longer with brodalumab (215 days; 95% CI: 197–233) vs ustekinumab (145 days; 95% CI: 130–160); adifference of 70 days (95% CI: 46–94; p < 0.001).
Conclusion
Using a novel multistate modelling approach based on absolute PASI, we found that patients had a greater probability of achieving and maintaining a response with brodalumab vs ustekinumab.
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Acknowledgements and disclosure
All authors participated in interpreting the results and writing the manuscript and approved the final version for submission. AstraZeneca was not involved in the decision to publish these analyses and did not participate in the preparation of this manuscript.
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Financial support
The brodalumab clinical study programme was sponsored by Amgen/AstraZeneca; this analysis was performed by LEO Pharma. Medical writing support was provided by Susan Dyas, MSc, from Adelphi Communications Limited and Matthew Hartmann, PhD from Alphabet Health (New York, NY), funded by LEO Pharma, in accordance with Good Publication Practice (GPP3) guidelines.
Conflicts of interest
Claus Zachariae has received honoraria as consultant and/or speaker from AbbVie, Almirall, Amgen, CSL, LEO Pharma, UCB, Eli Lilly, Novartis, Takeda and Janssen Pharmaceuticals. Ulrich Mrowietz has been an advisor and/or received speaker’s honoraria and/or received grants and/or participated in clinical trials of the following companies: AbbVie, Aditxt, Almirall, Amgen, Aristea, Boehringer-Ingelheim, Bristol-Myers Squibb, Celgene, Dr. Reddy’s, Eli Lilly, Foamix, Formycon, Immunic, Janssen, LEO Pharma, Medac, MetrioPharm, Novartis, Phi-Stone, Pierre Fabre, Sanofi-Aventis and UCB Pharma. Jens Strodl Andersen is an employee of LEO Pharma. Lluís Puig has received consultancy/speaker’s honoraria from and/or participated in clinical trials sponsored by AbbVie, Almirall, Amgen, Baxalta, Biogen, Boehringer Ingelheim, Celgene, Gebro, Janssen, JS BIOCAD, Leo-Pharma, Lilly, Merck-Serono, MSD, Mylan, Novartis, Pfizer, Regeneron, Roche, Sandoz, Samsung-Bioepis, Sanofi and UCB.
Supplementary data
Supplementary data associated with this article can be found, in the online version, at doi:10.1684/ejd.2022.4304. Supplementary figure 1 Study designs for the Phase III randomized controlled AMAGINE-2 and AMAGINE-3 trials of brodalumab in patients with moderate-to-severe psoriasis.
Q2W: every two weeks; Q4W: every four weeks; Q8W: every eight weeks; R: randomization.
Supplementary data
40699_2022_4304_MOESM1_ESM.pdf
Multistate modelling of probability of on-treatment clinical response and time remaining in response in patients with moderate-to-severe psoriasis treated with brodalumab or ustekinumab in the AMAGINE-2 and -3 studies
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Zachariae, C., Mrowietz, U., Strodl Andersen, J. et al. Multistate modelling of probability of on-treatment clinical response and time remaining in response in patients with moderate-to-severe psoriasis treated with brodalumab or ustekinumab in the AMAGINE-2 and -3 studies. Eur J Dermatol 32, 530–535 (2022). https://doi.org/10.1684/ejd.2022.4304
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DOI: https://doi.org/10.1684/ejd.2022.4304