Inefficiencies of Off-Label Therapy in the Prevention of Generalized Pustular Psoriasis (GPP) Flares: Real-World Evidence From Europe
Author(s)
Laurent Misery, MD, PhD1, Denis Jullien, MD, PhD2, Manuelle Viguier, MD, PhD3, Richard B. Warren, MBChB (Hons), PhD4, Christopher EM Griffiths, MD4, Michael Sticherling, MD, PhD5, Bhargav Lakshminarasimhan, PharmD, MBA6, Nichiren Pillai, MSc, MBA6, Shah Alam Khan, MPH, MSPH, MD6, Elke De Jong, MD, PhD7, Anna Balato, MD, PhD8, Stefano Piaserico, MD, PhD9.
1Department of Dermatology, Venereology and Allergology and French Expert Centre on Pruritus, University Hospital of Brest, Brest, France, 2Department of Dermatology, Faculty of Medicine Lyon-Est, Hôpital Edouard Herriot, University of Lyon, Lyon, France, 3Université de Reims- Champagne Ardenne, Service de Dermatologie, Hôpital Robert Debré, Reims, France, 4Dermatology Centre, Northern Care Alliance NHS Foundation Trust & Division of Musculoskeletal and Dermatological Sciences Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom, 5Hautklinik, Friedrich-Alexander-University of Erlangen-Nürnberg (FAU) Department of Dermatology, Deutsches Zentrum Immuntherapie (DZI), University Hospital Erlangen, Erlangen, Germany, 6Boehringer Ingelheim International GmbH, Ingelheim, Germany, 7Department of Dermatology, Radboud University Medical Center (Radboudumc), Nijmegen, Netherlands, 8Unit of Dermatology, University of Campania "Luigi Vanvitelli", Naples, Italy, 9Unit of Dermatology, University of Padua, Padua, Italy.
1Department of Dermatology, Venereology and Allergology and French Expert Centre on Pruritus, University Hospital of Brest, Brest, France, 2Department of Dermatology, Faculty of Medicine Lyon-Est, Hôpital Edouard Herriot, University of Lyon, Lyon, France, 3Université de Reims- Champagne Ardenne, Service de Dermatologie, Hôpital Robert Debré, Reims, France, 4Dermatology Centre, Northern Care Alliance NHS Foundation Trust & Division of Musculoskeletal and Dermatological Sciences Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom, 5Hautklinik, Friedrich-Alexander-University of Erlangen-Nürnberg (FAU) Department of Dermatology, Deutsches Zentrum Immuntherapie (DZI), University Hospital Erlangen, Erlangen, Germany, 6Boehringer Ingelheim International GmbH, Ingelheim, Germany, 7Department of Dermatology, Radboud University Medical Center (Radboudumc), Nijmegen, Netherlands, 8Unit of Dermatology, University of Campania "Luigi Vanvitelli", Naples, Italy, 9Unit of Dermatology, University of Padua, Padua, Italy.
OBJECTIVES: Generalized pustular psoriasis (GPP) is a chronic, systemic, neutrophilic inflammatory disease associated with significant morbidity and mortality. Patients experience a heterogenous and unpredictable clinical course, with periods of flaring. GPP is largely managed off-label using therapies for plaque psoriasis, despite being a distinct disease and the approval of targeted treatment (i.e., spesolimab) in 2022. Here, we describe real-world off-label treatment patterns in the prevention of GPP flares in Europe.
METHODS: SCRIPTOR was an international, retrospective, non-interventional, chart review of patients diagnosed with GPP from 2011 onwards (data extraction September 2021-August 2024). We investigated the reasons for terminating prescriptions of off-label therapies in flare prevention.
RESULTS: In total, 199 patients were screened in France (53.3%), Germany (22.1%), the UK (14.1%), Italy (9.5%), and the Netherlands (1.0%). Of 183 eligible patients, 103 patients had 475 prescriptions for off-label preventive therapy, including: retinoid (18.1%), methotrexate (16.4%), TNF biologic (13.3%), topical corticosteroid (11.6%), IL-17 biologic (9.3%), and oral corticosteroid (8.7%). Of 475 prescriptions, 321 were terminated. “Lack of efficacy” was the most common reason for terminating prescriptions of retinoid (24.2% [16/66] of retinoid prescriptions), methotrexate (29.6% [16/54]), TNF biologic (30.6% [15/49]), IL-17 biologic (41.2% [7/17]), IL-23 biologic (42.9% [6/14]), and topical treatment, e.g., emollient (83.3% [10/12]). Termination due to “adverse events” occurred most often with retinoid (22.7% [15/66]), cyclosporin (15.4% [4/26]), and PDE 4 inhibitor (66.7% [2/3]). The need for dose adjustment led to termination of 33.6% (108/321) of all prescriptions. “Dose reduction” was the main reason for terminating oral corticosteroid prescriptions (64.3% [18/28]). Median treatment duration ranged from 9 days (oral corticosteroid) to 5.1 months (TNF biologic).
CONCLUSIONS: Long-term GPP management with off-label therapies involves frequent dose adjustment, and discontinuations due to lack of efficacy and adverse events, that potentially negatively impact patient outcome. These findings highlight the need for targeted GPP therapy.
METHODS: SCRIPTOR was an international, retrospective, non-interventional, chart review of patients diagnosed with GPP from 2011 onwards (data extraction September 2021-August 2024). We investigated the reasons for terminating prescriptions of off-label therapies in flare prevention.
RESULTS: In total, 199 patients were screened in France (53.3%), Germany (22.1%), the UK (14.1%), Italy (9.5%), and the Netherlands (1.0%). Of 183 eligible patients, 103 patients had 475 prescriptions for off-label preventive therapy, including: retinoid (18.1%), methotrexate (16.4%), TNF biologic (13.3%), topical corticosteroid (11.6%), IL-17 biologic (9.3%), and oral corticosteroid (8.7%). Of 475 prescriptions, 321 were terminated. “Lack of efficacy” was the most common reason for terminating prescriptions of retinoid (24.2% [16/66] of retinoid prescriptions), methotrexate (29.6% [16/54]), TNF biologic (30.6% [15/49]), IL-17 biologic (41.2% [7/17]), IL-23 biologic (42.9% [6/14]), and topical treatment, e.g., emollient (83.3% [10/12]). Termination due to “adverse events” occurred most often with retinoid (22.7% [15/66]), cyclosporin (15.4% [4/26]), and PDE 4 inhibitor (66.7% [2/3]). The need for dose adjustment led to termination of 33.6% (108/321) of all prescriptions. “Dose reduction” was the main reason for terminating oral corticosteroid prescriptions (64.3% [18/28]). Median treatment duration ranged from 9 days (oral corticosteroid) to 5.1 months (TNF biologic).
CONCLUSIONS: Long-term GPP management with off-label therapies involves frequent dose adjustment, and discontinuations due to lack of efficacy and adverse events, that potentially negatively impact patient outcome. These findings highlight the need for targeted GPP therapy.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO152
Topic
Clinical Outcomes
Topic Subcategory
Clinician Reported Outcomes
Disease
Sensory System Disorders (Ear, Eye, Dental, Skin)