M Masson Regnault1, J Castañeda-Sanabria2, M H T Diep Tran2, M Beylot-Barry3, H Bachelez4,5,6, N Beneton7, O Chosidow8, A Dupuy9, P Joly10, D Jullien11, E Mahé12, M-A Richard13, M Viguier14, F Tubach2,15, E Sbidian8, C Paul1. 1. Dermatologie, CHU Toulouse, Toulouse, France. 2. Centre de Pharmaco-épidémiologie, Pitié Salpêtrière, Paris, France. 3. Dermatologie, CHU Bordeaux, Bordeaux, France. 4. Service de Dermatologie, AP-HP Hopital Saint Louis, Paris, France. 5. Sorbonne Paris Cité Université Paris Diderot, Paris, France. 6. UMR INSERM 1163, Institut Imagine, Paris, France. 7. Dermatologie, CHU Le Mans, Le Mans, France. 8. Dermatologie, AP-HP, Hôpitaux universitaires Henri Mondor, Département de Dermatologie, UPEC, INSERM, Centre d'Investigation Clinique 1430, EA 7379 EpidermE, Université Paris-Est Créteil, UPEC, Créteil, France. 9. Dermatologie, CHU Rennes, Rennes, France. 10. Dermatologie, CHU Rouen, Rouen, France. 11. Dermatologie, CHU Lyon, Lyon, France. 12. Dermatologie, CH Argenteuil, Argenteuil, France. 13. Dermatology Department, EA 3279: CEReSS - Health Service Research and Quality of Life Center, Timone Hospital, Assistance Publique Hôpitaux de Marseille, Aix-Marseille University, Marseille, France. 14. Dermatologie-Vénéréologie, Hôpital Robert Debré, Reims, France. 15. Sorbonne Université, INSERM UMR-S 1136, Paris, France.
Abstract
BACKGROUND: Numerous inclusion and exclusion criteria are involved in phase III moderate to severe psoriasis trials investigating the safety and efficacy of biologics. This questions the generalization of results. METHODS: In this cohort study, we applied inclusion/exclusion criteria for phase III trials from original protocols (adalimumab - REVEAL, ustekinumab - PHOENIX, brodalumab - AMAGINE, secukinumab FIXTURE) to all patients enrolled in the PsoBioTeq prospective registry who received a biological agent for the first time between July 2012 and November 2017. We then compared the efficacy, drug survival and occurrence of adverse events between patients who satisfied/did not satisfy the eligibility criteria for these phase III trials. RESULTS: A total of 1267 patients were enrolled, of whom 993 (78.4%) were not eligible for at least one RCT (randomized controlled trial) and 251 (19.1%) did not meet the PASI/PGA severity requirements. Apart from disease severity, the most frequent criteria resulting in exclusion were as follows: non-plaque psoriasis (12.6%), significant cardiac disease (8.4%), significant liver disease (7.3%), elevated liver enzymes (4.9-9.6%) and personal history of diabetes (9.2%). There was no difference in drug survival between the two groups. The incidence ratio of adverse events was significantly lower in eligible versus non-eligible patients [0.78 (95% CI 0.62-0.97) (P = 0.03)]. CONCLUSION: The majority of patients treated with biologics in the PsoBioTeq real-life registry would not have been eligible for phase III moderate to severe psoriasis trials. Patients not eligible for psoriasis phase III clinical trials have a higher incidence of adverse events.
BACKGROUND: Numerous inclusion and exclusion criteria are involved in phase III moderate to severe psoriasis trials investigating the safety and efficacy of biologics. This questions the generalization of results. METHODS: In this cohort study, we applied inclusion/exclusion criteria for phase III trials from original protocols (adalimumab - REVEAL, ustekinumab - PHOENIX, brodalumab - AMAGINE, secukinumab FIXTURE) to all patients enrolled in the PsoBioTeq prospective registry who received a biological agent for the first time between July 2012 and November 2017. We then compared the efficacy, drug survival and occurrence of adverse events between patients who satisfied/did not satisfy the eligibility criteria for these phase III trials. RESULTS: A total of 1267 patients were enrolled, of whom 993 (78.4%) were not eligible for at least one RCT (randomized controlled trial) and 251 (19.1%) did not meet the PASI/PGA severity requirements. Apart from disease severity, the most frequent criteria resulting in exclusion were as follows: non-plaque psoriasis (12.6%), significant cardiac disease (8.4%), significant liver disease (7.3%), elevated liver enzymes (4.9-9.6%) and personal history of diabetes (9.2%). There was no difference in drug survival between the two groups. The incidence ratio of adverse events was significantly lower in eligible versus non-eligible patients [0.78 (95% CI 0.62-0.97) (P = 0.03)]. CONCLUSION: The majority of patients treated with biologics in the PsoBioTeq real-life registry would not have been eligible for phase III moderate to severe psoriasis trials. Patients not eligible for psoriasis phase III clinical trials have a higher incidence of adverse events.
Authors: Thomas Graier; Wolfgang Weger; Paul-Gunther Sator; Wolfgang Salmhofer; Barbara Gruber; Constanze Jonak; Claudia Kölli; Martina Schütz-Bergmayr; Igor Vujic; Gudrun Ratzinger; Nina Häring; Clemens Painsi; Knut Prillinger; Alexander Mlynek; Hans Skvara; Hannes Trattner; Adrian Tanew; Roland Lichem; Christina Ellersdorfer; Franz Legat; Alexandra Gruber-Wackernagel; Angelika Hofer; Erich Schmiedberger; Wolfram Hoetzenecker; Robert Müllegger; Werner Saxinger; Franz Quehenberger; Peter Wolf Journal: JAAD Int Date: 2020-12-26
Authors: T Graier; W Weger; C Jonak; P Sator; C Zikeli; K Prillinger; C Sassmann; B Gruber; W Saxinger; G Ratzinger; C Painsi; A Mlynek; N Häring; B Sadoghi; H Trattner; R Müllegger; F Quehenberger; W Salmhofer; Peter Wolf Journal: Sci Rep Date: 2022-09-05 Impact factor: 4.996
Authors: A Blauvelt; C Paul; P van de Kerkhof; R B Warren; A B Gottlieb; R G Langley; F Brock; C Arendt; M Boehnlein; M Lebwohl; K Reich Journal: Br J Dermatol Date: 2020-09-06 Impact factor: 9.302