Why do we Discontinue Biologic Agents? A Retrospective Study of 11 Years
Abstract
Introduction: Biologic agents acquired a growing relevance in dermatology, however, adverse events (AE) and reasons to discontinue therapy are not completely known. The objective of this study is to analyse the reasons behind the discontinuation of biologics and characterize the AE in this population of patients.
Material and Methods: Descriptive observational study, including patients over 18-years-old under treatment with biologic agents in the Dermatology Department of Hospital de Santarém, Portugal, between January/2007 and December/2017. We analysed reasons for therapeutic discontinuation, defined as the omission of at least 2 consecutive administrations, whatever the reason implicated and whether or not proposed by the dermatologist.
Results: A total of 262 cycles of treatment were performed, in 138 patients (59.4% male, 40.6% female). Psoriasis was the most prevalent diagnosis (93.5% of the patients). Cycles of treatment with 8 biologic agents were analysed: etanercept (46.6%), adalimumab (31.3%) and ustekinumab (12.6%) were the most represented. During the study period, 167 suspensions were registered, for which 170 justifications were indicated. The most prevalent causes were: primary or secondary therapeutic failure (35,3%), AE (31.2%), factors related to the patient/noncompliance (17.1%), surgical intervention (7.1%) and excellent clinical response/absence of lesions (6.5%). Among therapeutic discontinuations motivated by AE (n=53), infections were the most frequent cause (35.8%, n=19), followed by malignancies (15.1%, n=8), hematological abnormalities (13.2%, n=7), neurological symptoms (9.4%, n=5) and local reactions at the injection site (5.7%, n=3).
Discussion: The main cause for discontinuation of biologics was therapeutic failure, immediately followed by AE. Two different patterns of discontinuation were apparent: definitive suspension, commonly decided by the physician due to primary or secondary therapeutic failure, and temporary discontinuation, frequently without formal medical indication, due to AE, later resuming the same drug. We found a higher percentage of therapeutic cycles discontinued due to AE than reported in the literature. Temporary suspensions of the biologics due to AE, often not sufficiently valued by the dermatologist, are probably under-recognized and contribute to a suboptimal pattern of use of biologics and worse clinical outcomes.
Downloads
References
Campanati A, Ganzetti G, Giuliodori K, Molinelli E, Offidani A. Biologic Therapy in Psoriasis: Safety Profile. Curr Drug Saf. 2016; 11:4-11.
Torres T, Filipe P, Basto AS, Fernandes JC, Ferreira A, Rosmaninho A, et al. The DRAGON study: biologic DRug survivAl in PortuGuese psOriasis patieNts. Eur J Dermatol. 2018; 28:685-87.
Yiu ZZN, Mason KJ, Hampton PJ, Reynolds NJ, Smith CH, Lunt M, et al. Drug survival of adalimumab, ustekinumab and secukinumab in patients with psoriasis: a prospective cohort study from the British Association of Dermatologists Biologics and Immunomodulators
Register (BADBIR). Br J Dermatol. 2020 (in press). doi: 10.1111/bjd.18981.
Sruamsiri R, Iwasaki K, Tang W, Mahlich J. Persistence rates and medical costs of biological therapies for psoriasis treatment in Japan: a real-world data study using a claims database. BMC Dermatol. 2018; 18:5. doi: 10.1186/s12895-018-0074-0.
Iskandar IYK, Ashcroft DM, Warren RB, Evans I, McElhone K, Owen CM, et al. Patterns of biologic therapy use in the management of psoriasis: cohort study from the British Association of Dermatologists biologic interventions register (BADBIR). Br J Dermatol. 2017;
:1297-307. doi: 10.1111/bjd.15027.
Torres T, Balato A, Conrad C, Conti A, Dapavo P, Ferreira P, et al. Secukinumab drug survival in patients with psoriasis: a multicenter, real-world, retrospective study. J Am Acad Dermatol. 2019; 81: 273-75.
Kishimoto M, Komine M, Kamiya K, Sugai J, Mieno M, Ohtsuki M. Drug survival of biologic agents for psoriatic patients in a real-world setting in Japan. J Dermatol. 2020;4733-40. doi: 10.1111/1346-8138.15146.
Pogácsás L, Borsi A, Takács P, Remenyik E, Kemény L, Kárpáti S, et al. Long-term drug survival and predictor analysis of the whole psoriatic patient population on biological therapy in Hungary. J Dermatolog Treat. 2017; 28:635-47.
Belinchón I, Ramos JM, Carretero G, Ferrándiz C, Rivera R, Dauden E, et al. Adverse events associated with discontinuation of the biologics/classic systemic treatments of moderate-severe plaque psoriasis: data from the Spanish Biologics Registry, Biobadaderm. J Eur Acad Dermatol Venereol. 2017;311700-8.
Doshi JA, Takeshita J, Pinto L, Li P, Yu X, Rao P, et al. Biologic therapy adherence, discontinuation, switching, and restarting among patients with psoriasis in the US Medicare population. J Am Acad Dermatol. 2016; 74:1057-65.
Lin P, Wang S, Chi C. Drug survival of biologics in treating psoriasis: a meta-analysis of real-world evidence. Sci Rep. 2018;8:16068. doi: 10.1038/s41598-018-34293-y.
Lunder T, Zorko MS, Kolar NK, Suhodolcan AB, Marovt M, Leskovec NK, et al. Drug survival of biological therapy is showing class effect: updated results from Slovenian National Registry of psoriasis. Int J Dermatol. 2019; 58:631-41. doi: 10.1111/ijd.14429.
Egeberg A, Ottosen M, Gniadecki R, Broesby-Olsen S, Dam TN, Bryld LE, et al. Safety, efficacy, and drug survival of biologics and biosimilars for moderate-to-severe plaque psoriasis. Br J Dermatol. 2018; 178:509-19. doi: 10.1111/bjd.16102.
Wolf D, Skup M, Yang H, Fang AP, Kageleiry A, Chao J. Clinical Outcomes Associated with Switching or Discontinuation from Anti-TNF Inhibitors for Nonmedical Reasons. Clin Ther. 2017; 39:849-62. doi: 10.1016/j.clinthera.2017.03.005.
Copyright (c) 2020 Journal of the Portuguese Society of Dermatology and Venereology
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
All articles in this journal are Open Access under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).
