Real-world use of dimethyl fumarate in patients with plaque psoriasis: a Delphi-based expert consensus
https://doi.org/10.4081/dr.2023.9613
HTML: 42
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Dimethyl fumarate (DMF) was recently approved by the European Medicines Agency for systemic treatment of moderateto- severe chronic plaque psoriasis. Appropriate management of DMF treatment is required to achieve optimal clinical benefits. 7 dermatology experts gathered online for 3 meetings to identify consensus on the use of DMF in patient selection, drug dosage/titration, side effects management, and follow-up, with the aim to provide guidance on the use of DMF for psoriasis in clinical dermatological practice based on literature data and expert opinion. 20 statements were discussed and voted on using a facilitator- mediated modified Delphi methodology. Strong consensus was reached for all statements (agreement level of 100%). DMF treatment is characterized by dosage flexibility, sustained efficacy, high rates of drug survival, and low potential for drug-drug interactions. It can be used in a broad range of patients, including the elderly or those with comorbidities. Side effects (mainly gastrointestinal disorders, flushing, and lymphopenia) are frequently reported but are generally mild and transient and can be minimized by dosage adjustments and a slow titration schedule. Hematologic monitoring throughout the treatment course is required to reduce the risk of lymphopenia. This consensus document provides clinical dermatologists with answers on the optimal use of DMF to treat psoriasis.
Korman NJ. Management of psoriasis as a systemic disease: what is the evidence? Br J Dermatol. 2020;182(4):840–848. https://doi.org/10.1111/bjd.18245
Mrowietz U, Szepietowski JC, Loewe R, et al. Efficacy and safety of LAS41008 (dimethyl fumarate) in adults with moderate-to-severe chronic plaque psoriasis: a randomized, double-blind, Fumaderm® - and placebo-controlled trial (BRIDGE). Br J Dermatol. 2017;176(3):615–623.
Griffiths CEM, Armstrong AW, Gudjonsson JE, et al. Psoriasis. Lancet. 2021;397(10281):1301–1315. https://doi.org/10.1016/S0140-6736(20)32549-6
Balak DMW. First-line systemic treatment of psoriasis: staying conventional or going biologic? Br J Dermatol. 2017;177(4):897–898.
European Medicines Agency [Internet]. Skilarence, INN-dimethyl fumarate: Summary of Product Characteristics. EMA 2017 [cited 2022 May 12]. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/skilarence#product-information-section.
Brück J, Dringen R, Amasuno A, et al. A review of the mechanisms of action of dimethylfumarate in the treatment of psoriasis. Exp Dermatol. 2018;27(6):611–624.
Blair HA. Dimethyl fumarate: a review in moderate to severe plaque psoriasis. Drugs. 2018;78(1):123–130.
Caputo V, Strafella C, Cosio T, et al. Pharmacogenomics: an update on biologics and small-molecule drugs in the treatment of psoriasis. Genes (Basel). 2021;12(9):1398.
Campione E, Mazzilli S, Di Prete M, et al. The role of glutathione-S transferase in psoriasis and associated comorbidities and the effect of dimethyl fumarate in this pathway. Front Med (Lausanne). 2022;9:760852.
van de Kerkhof PCM, Loewe R, Mrowietz U, et al. Quality of life outcomes in adults with moderate-to-severe plaque psoriasis treated with dimethylfumarate (DMF): a post hoc analysis of the BRIDGE study. J Eur Acad Dermatol Venereol. 2020;34(1):119–126.
Lijnen R, Otters E, Balak D, et al. Long-term safety and effectiveness of high-dose dimethylfumarate in the treatment of moderate to severe psoriasis: a prospective single-blinded follow-up study. J Dermatolog Treat. 2016;27(1):31–36.
Augustin M, Landeck L, Diemert S, et al. Long-term treatment with dimethyl fumarate for plaque psoriasis in routine practice: good overall effectiveness and positive effect on impactful areas. Dermatol Ther (Heidelb). 2022;12(5):1121–1131.
Reich K, Thaci D, Mrowietz U, et al. Efficacy and safety of fumaric acid esters in the long-term treatment of psoriasis—a retrospective study (FUTURE). J Dtsch Dermatol Ges. 2009;7(7):603–611.
Dickel H, Bruckner T, Altmeyer P. Long-term real-life safety profile and effectiveness of fumaric acid esters in psoriasis patients: a single-centre, retrospective, observational study. J Eur Acad Dermatol Venereol. 2018;32(10):1710–1727.
Ismail N, Collins P, Rogers S, et al. Drug survival of fumaric acid esters for psoriasis: a retrospective study. Br J Dermatol. 2014;171(2):397–402.
Nast A, Gisondi P, Ormerod AD, et al. European S3-Guidelines on the systemic treatment of psoriasis vulgaris – Update 2015 – Short version – EDF in cooperation with EADV and IPC. J Eur Acad Dermatol Venereol. 2015;29(12):2277–2294.
Malara G, Fabbrocini G, Trifirò C, et al. Dimethyl fumarate titration for the systemic treatment of moderate-to-severe plaque psoriasis. Drugs Context. 2021;10:2020-12-4.
McMillan SS, King M, Tully MP. How to use the nominal group and Delphi techniques. Int J Clin Pharm. 2016;38(3):655–662.
Mazzilli S, Cosio T, Botti E, et al. Dimethylfumarate efficacy and safety in palmoplantar psoriasis patient affected by hepatitis B and depression: a case report. Dermatol Ther. 2020;33(4):e13659.
Mrowietz U, Barker J, Boehncke WH, et al. Clinical use of dimethyl fumarate in moderate-to-severe plaque-type psoriasis: a European expert consensus. J Eur Acad Dermatol Venereol. 2018;32(Suppl 3):3–14.
Balato N, Patruno C, Napolitano M, et al. Managing moderate-to-severe psoriasis in the elderly. Drugs Aging. 2014;31(4):233–238.
Thaçi D, Weisenseel P, Philipp S, et al. Efficacy and safety of fumaric acid esters in patients with psoriasis on medication for comorbid conditions - a retrospective evaluation (FACTS). J Dtsch Dermatol Ges. 2013;11(5):429–435.
Corazza M, Odorici G, Conti A, et al. Dimethyl fumarate treatment for psoriasis in a real-life setting: a multicentric retrospective study. Dermatol Ther. 2021;34(5):e15066.
Ricceri F, Bardazzi F, Buggiani G, et al. Efficacy and safety of dimethylfumarate in elderly psoriasis patients: a multicentric Italian study. J Dermatolog Treat. [Published online 2021 Aug 11];1–4. doi: 10.1080/09546634.2021.1962000.
Gisondi P, Fostini AC, Fossà I, et al. Psoriasis and the metabolic syndrome. Clin Dermatol. 2018;36(1):21–28.
Holzer G, Hoke M, Sabeti-Sandor S, et al. Disparate effects of adalimumab and fumaric acid esters on cardiovascular risk factors in psoriasis patients: results from a prospective, randomized, observer-blinded head-to-head trial. J Eur Acad Dermatol Venereol. 2021;35(2):441–449.
Gold R, Phillips JT, Havrdova E, et al. Delayed-release dimethyl fumarate and pregnancy: preclinical studies and pregnancy outcomes from clinical trials and postmarketing experience. Neurol Ther. 2015;4(2):93–104.
Weisenseel P, Reich K, Griemberg W, et al. Efficacy and safety of fumaric acid esters in combination with phototherapy in patients with moderate-to-severe plaque psoriasis (FAST). J Dtsch Dermatol Ges. 2017;15(2):180–186.
Tzaneva S, Geroldinger A, Trattner H, et al. Fumaric acid esters in combination with a 6-week course of narrowband ultraviolet B provides an accelerated response compared with fumaric acid esters monotherapy in patients with moderate-to-severe plaque psoriasis: a randomized prospective clinical study. Br J Dermatol. 2018;178(3):682–688.
Balak DMW, Gerdes S, Parodi A, et al. Long-term safety of oral systemic therapies for psoriasis: a comprehensive review of the Literature. Dermatol Ther (Heidelb). 2020;10(4):589–613.
Reszke R, Szepietowski JC. A safety evaluation of dimethyl fumarate in moderate-to-severe psoriasis. Expert Opin Drug Saf. 2020;19(4):373–380.
Dickel H, Bruckner T, Höxtermann S, et al. Fumaric acid ester-induced T-cell lymphopenia in the real-life treatment of psoriasis. J Eur Acad Dermatol Venereol. 2019;33(5):893–905.
Reich K, Mrowietz U, Radtke MA, et al. Drug safety of systemic treatments for psoriasis: results from The German Psoriasis Registry PsoBest. Arch Dermatol Res. 2015;307(10):875–883.
Arnold T, Schaarschmidt ML, Herr R, et al. Drug survival rates and reasons for drug discontinuation in psoriasis. J Dtsch Dermatol Ges. 2016;14(11):1089–1099. https://doi.org/10.1111/ddg.13152
Copyright (c) 2022 the Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
Downloads
Citations
