Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Dermatology and Therapy
Published in: Dermatology and Therapy 4/2020

Open Access 01-08-2020 | Systemic Therapy | Review

Long-term Safety of Oral Systemic Therapies for Psoriasis: A Comprehensive Review of the Literature

Authors: Deepak M. W. Balak, Sascha Gerdes, Aurora Parodi, Laura Salgado-Boquete

Published in: Dermatology and Therapy | Issue 4/2020

Login to get access

Abstract

Oral systemic therapies are important treatment options for patients with moderate-to-severe psoriasis, either as monotherapy or in therapy-recalcitrant cases as combination therapy with phototherapy, other oral systemics or biologics. Long-term treatment is needed to maintain sufficient disease control in psoriasis, but continuous use of systemic treatments is limited by adverse events (AEs) and cumulative toxicity risks. The primary aim of this comprehensive literature review was to examine the long-term safety profiles of oral agents commonly used in the treatment of adults with psoriasis. Searches were conducted in EMBASE and PubMed up to November 2018, and 157 relevant publications were included. Long-term treatment with acitretin could be associated with skeletal toxicity and hepatotoxicity, although evidence for skeletal toxicity is mixed and hepatotoxicity is rare, particularly at low doses. Other safety issues include hyperlipidaemia and potential for teratogenicity up to 2–3 years after discontinuation of treatment. There is a paucity of data on long-term treatment with apremilast. Continued exposure to apremilast does not seem to increase the incidence of common AEs, such as gastrointestinal (GI) AEs, upper respiratory tract infections and headache, while the long-term risks for depression, suicidal thoughts and weight loss are unknown. Long-term ciclosporin treatment is associated with renal toxicity, hypertension, non-melanoma skin cancer, neurological AEs and GI AEs. Long-term methotrexate treatment is associated with hepatotoxicity, GI AEs, haematological toxicity, renal toxicity and alopecia. Finally, long-term treatment with fumaric acid esters (FAE) is associated with GI AEs, flushing, lymphocytopenia, proteinuria and elevated liver enzymes. Median drug survival estimates varied considerably: ~  2.9–9.7 months for apremilast; ~ 5.4 months for ciclosporin; ~ 8.6 months for acitretin; ~ 12.1–21.6 months for methotrexate; and ~  54.8 months for FAE. These long-term safety profiles may help to guide clinicians to select the optimal oral systemic treatment for the long-term treatment of psoriasis in adults.
Appendix
Available only for authorised users
Literature
1.
Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 6. Guidelines of care for the treatment of psoriasis and psoriatic arthritis: case-based presentations and evidence-based conclusions. J Am Acad Dermatol. 2011;65(1):137–74.PubMedCrossRef
2.
Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 4. Guidelines of care for the management and treatment of psoriasis with traditional systemic agents. J Am Acad Dermatol. 2009;61(3):451–85.PubMedCrossRef
3.
Nakamura M, Koo J. Safety considerations with combination therapies for psoriasis. Expert Opin Drug Saf. 2020;19(4):489–98.
4.
Gustafson CJ, Watkins C, Hix E, Feldman SR. Combination therapy in psoriasis: an evidence-based review. Am J Clin Dermatol. 2013;14(1):9–25.PubMedCrossRef
5.
Armstrong AW, Bagel J, Van Voorhees AS, Robertson AD, Yamauchi PS. Combining biologic therapies with other systemic treatments in psoriasis: evidence-based, best-practice recommendations from the Medical Board of the National Psoriasis Foundation. JAMA Dermatol. 2015;151(4):432–8.PubMedCrossRef
6.
Edmundson WF, Guy WB. Treatment of psoriasis with folic acid antagonists. AMA Arch Dermatol. 1958;78(2):200–3.CrossRef
7.
Nast A, Amelunxen L, Augustin M, et al. S3 Guideline for the treatment of psoriasis vulgaris, update—short version part 1—systemic treatment. J Dtsch Dermatol Ges. 2018;16(5):645–69.PubMed
8.
9.
Augustin M, Spehr C, Radtke MA, et al. German psoriasis registry PsoBest: objectives, methodology and baseline data. J Dtsch Dermatol Ges. 2014;12(1):48–57.PubMed
10.
Iskandar IY, Ashcroft DM, Warren RB, et al. Demographics and disease characteristics of patients with psoriasis enrolled in the British Association of Dermatologists Biologic Interventions Register. Br J Dermatol. 2015;173(2):510–8.PubMedCrossRef
11.
12.
13.
Strober B, Ryan C, van de Kerkhof P, et al. Recategorization of psoriasis severity: Delphi consensus from the International Psoriasis Council. J Am Acad Dermatol. 2020;82(1):117–22.PubMedCrossRef
14.
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):2277–94.PubMedCrossRef
15.
Armstrong AW, Koning JW, Rowse S, Tan H, Mamolo C, Kaur M. Initiation, switching, and cessation of psoriasis treatments among patients with moderate to severe psoriasis in the United States. Clin Drug Investig. 2017;37(5):493–501.PubMedCrossRef
16.
Smith D. Fumaric acid esters for psoriasis: a systematic review. Ir J Med Sci. 2017;186(1):161–77.PubMedCrossRef
17.
Arnold T, Schaarschmidt ML, Herr R, Fischer JE, Goerdt S, Peitsch WK. Drug survival rates and reasons for drug discontinuation in psoriasis. J Dtsch Dermatol Ges. 2016;14(11):1089–99.PubMedCrossRef
18.
Sadovsky R. Cyclosporine in the treatment of dermatologic disease. Am Fam Phys. 1997;55(6):2306–7.
19.
Lee CS, Koo J. A review of acitretin, a systemic retinoid for the treatment of psoriasis. Expert Opin Pharmacother. 2005;6(10):1725–34.PubMedCrossRef
20.
Naldi L, Griffiths CEM. Traditional therapies in the management of moderate to severe chronic plaque psoriasis: an assessment of the benefits and risks. Br J Dermatol. 2005;152(4):597–615.PubMedCrossRef
21.
McClure SL, Valentine J, Gordon KB. Comparative tolerability of systemic treatments for plaque-type psoriasis. Drug Saf. 2002;25(13):913–27.PubMedCrossRef
22.
23.
Kaushik SB, Lebwohl MG. Review of safety and efficacy of approved systemic psoriasis therapies. Int J Dermatol. 2018;58(6):649–58.PubMedCrossRef
24.
Lebwohl M. A clinician's paradigm in the treatment of psoriasis. J Am Acad Dermatol. 2005;53(1 Suppl):S59–S69.PubMedCrossRef
25.
Geilen CC, Orfanos CE. Standard and innovative therapy of psoriasis. Clin Exp Dermatol. 2002;20(6 Suppl 28):S81–S8787.
26.
Maryles S, Rozenblit M, Lebwohl M. Transition from methotrexate and cyclosporine to other therapies including retinoids, ultraviolet light and biologic agents in the management of patients with psoriasis. J Dermatolog Treat. 2003;14(Suppl 2):7–16.PubMedCrossRef
27.
Blauvelt A, Armstrong AW, Krueger GG. Essential truths for the care and management of moderate-to-severe psoriasis. J Drugs Dermatol. 2015;14(8):805–12.PubMed
28.
29.
Nast A, Spuls PI, van der Kraaij G, et al. European S3-Guideline on the systemic treatment of psoriasis vulgaris—update apremilast and secukinumab—EDF in cooperation with EADV and IPC. J Eur Acad Dermatol Venereol. 2017;31(12):1951–63.PubMedCrossRef
30.
31.
Volc S, Ghoreschi K. Pathophysiological basis of systemic treatments in psoriasis. J Dtsch Dermatol Ges. 2016;14(6):557–72.PubMed
32.
33.
Crowley J, Thaçi D, Joly P, et al. Long-term safety and tolerability of apremilast in patients with psoriasis: pooled safety analysis for ≥156 weeks from 2 phase 3, randomized, controlled trials (ESTEEM 1 and 2). J Am Acad Dermatol. 2017;77(2):310–17.e1.PubMedCrossRef
34.
35.
Ryan C, Amor KT, Menter A. The use of cyclosporine in dermatology: part II. J Am Acad Dermatol. 2010;63(6):949–72.PubMedCrossRef
36.
Pathirana D, Ormerod AD, Saiag P, et al. European S3-guidelines on the systemic treatment of psoriasis vulgaris. J Eur Acad Dermatol Venereol. 2009;23(Suppl 2):1–70.PubMedCrossRef
37.
Feldman SR, Garton R. Cyclosporin in psoriasis: how? J Eur Acad Dermatol Venereol. 2004;18(3):250–3.PubMedCrossRef
38.
39.
Malatjalian DA, Ross JB, Williams CN, Colwell SJ, Eastwood BJ. Methotrexate hepatotoxicity in psoriatics: report of 104 patients from Nova Scotia, with analysis of risks from obesity, diabetes and alcohol consumption during long term follow-up. Can J Gastroenterol. 1996;10(6):369–75.PubMedCrossRef
40.
Haustein UF, Rytter M. Methotrexate in psoriasis: 26 years' experience with low-dose long-term treatment. J Eur Acad Dermatol Venereol. 2000;14(5):382–8.PubMedCrossRef
41.
Rajnics P, Kellner VS, Kellner A, Karadi E, Kollar B, Egyed M. The hematologic toxicity of methotrexate in patients with autoimmune disorders. J Neoplasm. 2017;2(1):1.CrossRef
42.
43.
Kalb RE, Strober B, Weinstein G, Lebwohl M. Methotrexate and psoriasis: 2009 National Psoriasis Foundation Consensus Conference. J Am Acad Dermatol. 2009;60(5):824–37.PubMedCrossRef
44.
Przekop PR Jr, Tulgan H, Przekop AA, Glantz M. Adverse drug reaction to methotrexate: pharmacogenetic origin. J Am Osteopath Assoc. 2006;106(12):706–7.PubMed
45.
46.
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.PubMedCrossRef
47.
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):429–35.PubMed
48.
49.
50.
51.
Koo J. Systemic sequential therapy of psoriasis: a new paradigm for improved therapeutic results. J Am Acad Dermatol. 1999;41(3 Pt 2):S25–S2828.PubMedCrossRef
52.
53.
Lee E, Loo J. Single-center retrospective study of long-term use of low-dose acitretin (Soriatane®) for psoriasis. J Drugs Dermatol. 2004;15(1):8–13.
54.
Katz HI, Waalen J, Leach EE. Acitretin in psoriasis: an overview of adverse effects. J Am Acad Dermatol. 1999;41(3 Pt 2):S7–S12.PubMedCrossRef
55.
Roenigk HH Jr, Callen JP, Guzzo CA, et al. Effects of acitretin on the liver. J Am Acad Dermatol. 1999;41(4):584–8.PubMedCrossRef
56.
Murray HE, Anhalt AW, Lessard R, et al. A 12-month treatment of severe psoriasis with acitretin: results of a Canadian open multicenter study. J Am Acad Dermatol. 1991;24(4):598–602.PubMedCrossRef
57.
Gollnick HP. Oral retinoids—efficacy and toxicity in psoriasis. Br J Dermatol. 1996;135(Suppl 49):6–17.PubMedCrossRef
58.
59.
Gupta AK, Goldfarb MT, Ellis CN, Voorhees JJ. Side-effect profile of acitretin therapy in psoriasis. J Am Acad Dermatol. 1989;20(6):1088–93.PubMedCrossRef
60.
Dávila-Seijo P, Dauden E, Descalzo MA, et al. Infections in moderate to severe psoriasis patients treated with biological drugs compared to classic systemic drugs: findings from the BIOBADADERM Registry. J Invest Dermatol. 2017;137(2):313–21.PubMedCrossRef
61.
Gisondi P, Girolomoni G. Biologic therapies in psoriasis: a new therapeutic approach. Autoimmun Rev. 2007;6(8):515–9.PubMedCrossRef
62.
Aryal A, Upreti S. A brief review on systemic retinoids. Int J Pharm Sci Res. 2017;8(9):3630–9.
63.
Reich K, Gooderham M, Green L, et al. The efficacy and safety of apremilast, etanercept and placebo in patients with moderate-to-severe plaque psoriasis: 52-week results from a phase IIIb, randomized, placebo-controlled trial (LIBERATE). J Eur Acad Dermatol Venereol. 2017;31(3):507–17.PubMedCrossRef
64.
Papp K, Reich K, Leonardi CL, et al. Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: Results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1). J Am Acad Dermatol. 2015;73(1):37–49.PubMedCrossRef
65.
66.
Reich K, Goodfield M, Green L, et al. Safety and efficacy of apremilast through 104 weeks in patients with moderate to severe psoriasis who continued on apremilast or switched from etanercept treatment in the LIBERATE study. Ann Rheum Dis. 2017;76:1325–6 (abstract AB0771).
67.
Elise Kleyn C, Laws P, Chen KS, Eccles J, Cordey M, Griffiths CEM. UK and Ireland real-world experience with apremilast in psoriasis patients: analysis of 126 patients from the APPRECIATE study. Br J Dermatol. 2018;179:63.
68.
Mayba JN, Gooderham MJ. Real-world experience with apremilast in treating psoriasis. J Cutan Med Surg. 2017;21(2):145–51.PubMedCrossRef
69.
Cranwell W, Radulski B, Dolianitis C, Nicolopoulos J, Varigos GA. Experience with apremilast in a small cohort of patients with chronic plaque psoriasis. Australas J Dermatol. 2018;59(S1):51.
70.
Ighani A, Georgakopoulos JR, Shear NH, Walsh S, Yeung J. Short-term reasons for withdrawal and adverse events associated with apremilast therapy for psoriasis in real-world practice compared with in clinical trials: a multicenter retrospective study. J Am Acad Dermatol. 2018;78(4):801–3.PubMedCrossRef
71.
Deeks ED. Apremilast: a review in psoriasis and psoriatic arthritis. Drugs. 2015;75(12):1393–403.PubMedCrossRef
72.
73.
Capella GL, Della Casa-Alberighi O, Finzi AF. Therapeutic concepts in clinical dermatology: cyclosporine A in immunomediated and other dermatoses. Int J Dermatol. 2001;40(9):551–61.PubMedCrossRef
74.
Weinstein GD, White GM. An approach to the treatment of moderate to severe psoriasis with rotational therapy. J Am Acad Dermatol. 1993;28(3):454–9.PubMedCrossRef
75.
76.
Ho VCY, Griffiths CEM, Berth-Jones J, et al. Intermittent short courses of cyclosporine microemulsion for the long-term management of psoriasis: a 2-year cohort study. J Am Acad Dermatol. 2001;44(4):643–51.PubMedCrossRef
77.
Paul CF, Ho VC, McGeown C, et al. Risk of malignancies in psoriasis patients treated with cyclosporine: a 5 y cohort study. J Invest Dermatol. 2003;120(2):211–6.PubMedCrossRef
78.
Marcil I, Stern RS. Squamous-cell cancer of the skin in patients given PUVA and ciclosporin: nested cohort crossover study. Lancet. 2001;358(9287):1042–5.PubMedCrossRef
79.
Zachariae H, Kragballe K, Hansen HE, Marcussen N, Olsen S. Renal biopsy findings in long-term cyclosporin treatment of psoriasis. Br J Dermatol. 1997;136(4):531–5.PubMedCrossRef
80.
Feutren G, Mihatsch MJ. Risk factors for cyclosporine-induced nephropathy in patients with autoimmune diseases. International Kidney Biopsy Registry of Cyclosporine in Autoimmune Diseases. New Engl J Med. 1992;326(25):1654–60.PubMedCrossRef
81.
Magnasco A, Rossi A, Catarsi P, et al. Cyclosporin and organ specific toxicity: Clinical apects, pharmacogenetics and perspectives. Curr Clin Pharmacol. 2008;3(3):166–73.PubMedCrossRef
82.
Laburte C, Grossman R, Abi-Rached J, Abeywickrama KH, Dubertret L. Efficacy and safety of oral cyclosporin A (CyA; Sandimmun) for long-term treatment of chronic severe plaque psoriasis. Br J Dermatol. 1994;130(3):366–75.PubMedCrossRef
83.
Maza A, Montaudie H, Sbidian E, et al. Oral cyclosporin in psoriasis: a systematic review on treatment modalities, risk of kidney toxicity and evidence for use in non-plaque psoriasis. J Eur Acad Dermatol Venereol. 2011;25(Suppl 2):19–27.PubMedCrossRef
84.
Powles H, Porter C, Hulme F. Renal function after 10 years’ treatment with cyclosporin for psoriasis. Br J Dermatol. 1998;138(3):443–9.PubMedCrossRef
85.
International Kidney Biopsy Registry of Cyclosporin A (Sandimmun®) in Autoimmune Diseases. Kidney biopsies in control or cyclosporin A-treated psoriatic patients. Br J Dermatol. 1990;122(Suppl 36):95–100.
86.
Lowe NJ, Wieder JM, Rosenbach A, et al. Long-term low-dose cyclosporine therapy for severe psoriasis: effects on renal function and structure. J Am Acad Dermatol. 1996;35(5 Pt 1):710–9.PubMedCrossRef
87.
Mrowietz U, Farber L, Henneicke-von Zepelin HH, Bachmann H, Welzel D, Christophers E. Long-term maintenance therapy with cyclosporine and post-treatment survey in severe psoriasis: results of a multicenter study. German Multicenter Study. J Am Acad Dermatol. 1995;33(3):470–5.PubMedCrossRef
88.
Pei Y, Scholey JW, Katz A, Schachter R, Murphy GF, Cattran D. Chronic nephrotoxicity in psoriatic patients treated with low-dose cyclosporine. Am J Kidney Dis. 1994;23(4):528–36.PubMedCrossRef
89.
Powles AV, Baker BS, Valdimarsson H, Hulme B, Fry L. Four years of experience with cyclosporin A for psoriasis. Br J Dermatol. 1990;122(Suppl 36):13–9.PubMedCrossRef
90.
Powles AV, Cook T, Hulme B, et al. Renal function and biopsy findings after 5 years' treatment with low-dose cyclosporin for psoriasis. Br J Dermatol. 1993;128(2):159–65.PubMedCrossRef
91.
Shupack J, Abel E, Bauer E, et al. Cyclosporine as maintenance therapy in patients with severe psoriasis. J Am Acad Dermatol. 1997;36(3 Pt 1):423–32.PubMedCrossRef
92.
Svarstad E, Helland S, Morken T, et al. Renal effects of maintenance low-dose cyclosporin A treatment in psoriasis. Nephrol Dial Transplant. 1994;9(10):1462–7.PubMed
93.
Grossman RM, Chevret S, Abi-Rached J, Blanchet F, Dubertret L. Long-term safety of cyclosporine in the treatment of psoriasis. Arch Dermatol. 1996;132(6):623–9.PubMedCrossRef
94.
Feutren G. The optimal use of cyclosporin A in autoimmune diseases. J Autoimmun. 1992;5(Suppl A):183–95.PubMedCrossRef
95.
Feutren G, Abeywickrama K, Friend D, von Graffenried B. Renal function and blood pressure in psoriatic patients treated with cyclosporin A. Br J Dermatol. 1990;122(Suppl 36):57–69.PubMedCrossRef
96.
Korstanje MJ, Van de Staak WJBM. Long-term treatment of psoriasis with cyclosporin A–side-effects, minimal effective dose and cyclosporin blood levels. Clin Exp Dermatol. 1991;16(1):8–10.PubMedCrossRef
97.
98.
Altomare G, Ayala F, Bardazzi F, et al. Consensus on the use of cyclosporine in dermatological practice. G Ital Dermatol Venereol. 2014;149(5):607–25.PubMed
99.
Lebwohl M, Ellis C, Gottlieb A, et al. Cyclosporine consensus conference: with emphasis on the treatment of psoriasis. J Am Acad Dermatol. 1998;39(3):464–75.PubMedCrossRef
100.
Geller S, Xu H, Lebwohl M, Nardone B, Lacouture ME, Kheterpal M. Malignancy risk and recurrence with psoriasis and its treatments: a concise update. Am J Clin Dermatol. 2018;19(3):363–75.PubMedPubMedCentralCrossRef
101.
Naldi L. Malignancy concerns with psoriasis treatments using phototherapy, methotrexate, cyclosporin, and biologics: facts and controversies. Clin Dermatol. 2010;28(1):88–92.PubMedCrossRef
102.
van de Kerkhof PCM. Consistent control of psoriasis by continuous long-term therapy: The promise of biological treatments. J Eur Acad Dermatol Venereol. 2006;20(6):639–50.PubMedCrossRef
103.
Vassantachart JM, Jacob SE. Cyclosporine in the treatment of psoriasis. J Dermatol Nurses Assoc. 2017;9(2):98–101.CrossRef
104.
Colombo D, Banfi G, Cassano N, et al. The GENDER ATTENTION observational study: gender and hormonal status differences in the incidence of adverse events during cyclosporine treatment in psoriatic patients. Adv Ther. 2017;34(6):1349–63.PubMedPubMedCentralCrossRef
105.
Christophers E, Mrowietz U, Henneicke HH, Färber L, Welzel D. Cyclosporine in psoriasis: a multicenter dose-finding study in severe plaque psoriasis. The German Multicenter Study. J Am Acad Dermatol. 1992;26(1):86–90.PubMedCrossRef
106.
Korstanje MJ. How to improve the risk–benefit ratio of cyclosporin therapy for psoriasis. Clin Exp Dermatol. 1992;17(1):16–9.PubMedCrossRef
107.
108.
Cipriani P, Ruscitti P, Carubbi F, Liakouli V, Giacomelli R. Methotrexate: an old new drug in autoimmune disease. Expert Rev Clin Immunol. 2014;10(11):1519–30.PubMedCrossRef
109.
Ajmani S, Preet Singh Y, Prasad S, et al. Methotrexate-induced pancytopenia: a case series of 46 patients. Int J Rheum Dis. 2017;20(7):846–51.PubMedCrossRef
110.
Kozub P, Simaljakova M. Systemic therapy of psoriasis: methotrexate. Bratisl Lek Listy. 2011;112(7):390–4.PubMed
111.
Cuellar ML, Espinoza LR. Methotrexate use in psoriasis and psoriatic arthritis. Rheum Dis Clin N Am. 1997;23(4):797–809.CrossRef
112.
Warren RB, Mrowietz U, von Kiedrowski R, et al. An intensified dosing schedule of subcutaneous methotrexate in patients with moderate to severe plaque-type psoriasis (METOP): a 52 week, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;389(10068):528–37.PubMedCrossRef
113.
114.
Weinstein G, Roenigk H, Maibach H, et al. Psoriasis-liver-methotrexate interactions. Arch Dermatol. 1973;108(1):36–42.CrossRef
115.
Lanse SB, Arnold GL, Gowans JD, Kaplan MM. Low incidence of hepatotoxicity associated with long-term, low-dose oral methotrexate in treatment of refractory psoriasis, psoriatic arthritis, and rheumatoid arthritis. An acceptable risk/benefit ratio. Dig Dis Sci. 1985;30(2):104–9.PubMedCrossRef
116.
Robinson JK, Baughman RD, Auerbach R, Cimis RJ. Methotrexate hepatotoxicity in psoriasis. Consideration of liver biopsies at regular intervals. Arch Dermatol. 1980;116(4):413–5.PubMedCrossRef
117.
Roenigk HH Jr, Auerbach R, Maibach HI, Weinstein GD. Methotrexate in psoriasis: revised guidelines. J Am Acad Dermatol. 1988;19(1 Pt 1):145–56.PubMedCrossRef
118.
119.
Zachariae H, Søgaard H. Methotrexate-induced liver cirrhosis. A follow-up. Dermatologica. 1987;175(4):178–82.PubMedCrossRef
120.
121.
Strober BE. Methotrexate-induced liver toxicity: replacing the liver biopsy. JAMA Dermatol. 2014;150(8):862–3.PubMedCrossRef
122.
Barker J, Horn EJ, Lebwohl M, et al. Assessment and management of methotrexate hepatotoxicity in psoriasis patients: Report from a consensus conference to evaluate current practice and identify key questions toward optimizing methotrexate use in the clinic. J Eur Acad Dermatol Venereol. 2011;25(7):758–64.PubMedCrossRef
123.
Eswaran R, Mahesh AR, Premkumar K, et al. Transient elastography monitoring for liver complications of long-term methotrexate use in psoriasis patients. Hepatol Int. 2018;12(2):S221.
124.
Warren RB, Weatherhead SC, Smith CH, et al. British Association of Dermatologists' guidelines for the safe and effective prescribing of methotrexate for skin disease 2016. Br J Dermatol. 2016;175(1):23–44.PubMedCrossRef
125.
126.
Shen S, O'Brien T, Yap LM, Prince HM, McCormack CJ. The use of methotrexate in dermatology: a review. Australas J Dermatol. 2012;53(1):1–18.PubMedCrossRef
127.
Roenigk HH Jr, Auerbach R, Maibach H, Weinstein G, Lebwohl M. Methotrexate in psoriasis: consensus conference. J Am Acad Dermatol. 1998;38(3):478–85.PubMedCrossRef
128.
Phillips TJ, Jones DH, Baker H. Pulmonary complications following methotrexate therapy. J Am Acad Dermatol. 1987;16(2 Pt 1):373–5.PubMedCrossRef
129.
Stern RS, Laird N. The carcinogenic risk of treatments for severe psoriasis. Photochemotherapy Follow-up Study Cancer. 1994;73(11):2759–64.PubMed
130.
Guenther L, Langley RG, Shear NH, et al. Integrating biologic agents into management of moderate-to-severe psoriasis: a consensus of the Canadian Psoriasis Expert Panel. J Cutan Med Surg. 2004;8(5):321–37.PubMedCrossRef
131.
Liu B, Schwartz RA. Potential cardio-protective effects of psoriasis medications. Acta Dermatovenerol Croat. 2018;26(3):249–54.PubMed
132.
De Vecchis R, Baldi C, Palmisani L. Protective effects of methotrexate against ischemic cardiovascular disorders in patients treated for rheumatoid arthritis or psoriasis: novel therapeutic insights coming from a meta-analysis of the literature data. Anatol J Cardiol. 2016;16(1):2–9.PubMed
133.
Micha R, Imamura F, Wyler von Ballmoos M, et al. Systematic review and meta-analysis of methotrexate use and risk of cardiovascular disease. Am J Cardiol. 2011;108(9):1362–70.PubMedPubMedCentralCrossRef
134.
Prodanovich S, Ma F, Taylor JR, Pezon C, Fasihi T, Kirsner RS. Methotrexate reduces incidence of vascular diseases in veterans with psoriasis or rheumatoid arthritis. J Am Acad Dermatol. 2005;52(2):262–7.PubMedCrossRef
135.
Busger op Vollenbroek FTM, Doggen CJM, Janssens RWA, Bernelot Moens HJ. Dermatological guidelines for monitoring methotrexate treatment reduce drug-survival compared to rheumatological guidelines. PLoS ONE. 2018;13(3):e0194401.PubMedPubMedCentralCrossRef
136.
137.
Lucas J, Ntuen E, Pearce DJ, Fleischer AB Jr, Feldman SR. Methotrexate: understanding the risk in psoriasis patients. J Dermatolog Treat. 2009;20(5):311–3.PubMedCrossRef
138.
139.
Brück J, Dringen R, Amasuno A, Pau-Charles I, Ghoreschi K. A review of the mechanisms of action of dimethylfumarate in the treatment of psoriasis. Exp Dermatol. 2018;27(6):611–24.PubMedCrossRef
140.
Mrowietz U, Morrison PJ, Suhrkamp I, Kumanova M, Clement B. The pharmacokinetics of fumaric acid esters reveal their in vivo effects. Trends Pharmacol Sci. 2018;39(1):1–12.PubMedCrossRef
141.
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):1710–27.PubMedPubMedCentralCrossRef
142.
Hoefnagel JJ, Thio HB, Willemze R, Bouwes Bavinck JN. Long-term safety aspects of systemic therapy with fumaric acid esters in severe psoriasis. Br J Dermatol. 2003;149(2):363–9.PubMedCrossRef
143.
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):615–23.PubMedCrossRef
144.
Lijnen R, Otters E, Balak D, Thio B. 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):31–6.PubMedCrossRef
145.
Atwan A, Ingram JR, Abbott R, et al. Oral fumaric acid esters for psoriasis. Cochrane Database Syst Rev. 2015;2015(8):CD010497.PubMedPubMedCentral
146.
Burden-Teh E, Lam M, Cohen S. Fumaric acid esters to treat psoriasis: experience in a UK teaching hospital. J Am Acad Dermatol. 2013;68(4, Suppl 1):AB52.
147.
Philipp S, Wolk K, Sterry G, Sterry W, Sabat R. Analysis of patients under long term treatment with fumaric acid esters for upto 4 years. Exp Dermatol. 2010;19(2):195.
148.
Shear NH. Fulfilling an unmet need in psoriasis. Do biologicals hold the key to improved tolerability? Drug Saf. 2006;29(1):49–66.PubMedCrossRef
149.
Mason KJ, Lunt M, Hunter HJ, et al. Real-world use of fumaric acid esters in psoriasis: Results from the British Association of Dermatologists Biologic Interventions Register (BADBIR). Br J Dermatol. 2017;177(5):e272–e273.
150.
Mrowietz U, Christophers E, Altmeyer P. Treatment of severe psoriasis with fumaric acid esters: scientific background and guidelines for therapeutic use. The German Fumaric Acid Ester Consensus Conference. Br J Dermatol. 1999;141(3):424–9.PubMedCrossRef
151.
Reszke R, Szepietowski JC. A safety evaluation of dimethyl fumarate in moderate-to-severe psoriasis. Expert Opin Drug Saf. 2020;19(4):373–80.
152.
Reich K, Thaci D, Mrowietz U, Kamps A, Neureither M, Luger T. 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):603–11.PubMed
153.
Gieselbach RJ, Muller-Hansma AH, Wijburg MT, et al. Progressive multifocal leukoencephalopathy in patients treated with fumaric acid esters: a review of 19 cases. J Neurol. 2017;264(6):1155–64.PubMedCrossRef
154.
Nast A, Kopp IB, Augustin M, et al. Evidence-based (S3) guidelines for the treatment of psoriasis vulgaris. J Dtsch Dermatol Ges. 2007;5(Suppl 3):1–119.PubMedCrossRef
155.
Aubets J, Jansat JM, Salva M, et al. No evidence for interactions of dimethylfumarate (DMF) and its main metabolite monomethylfumarate (MMF) with human cytochrome P450 (CYP) enzymes and the P-glycoprotein (P-gp) drug transporter. Pharmacol Res Perspect. 2019;7(6):e00540.PubMedPubMedCentralCrossRef
156.
Sbidian E, Chaimani A, Garcia-Doval I, et al. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis. Cochrane Database Syst Rev. 2017;12:CD011535.PubMed
157.
Augustin M, Mrowietz U, Radtke MA, et al. Effectiveness, drug survival and safety of fumaric acid esters for moderate-to-severe psoriasis in routine care: results from the German Psoriasis Registry PsoBest. Br J Dermatol. 2017;177(5):e246–e247247.
158.
159.
Dávila-Seijo P, Dauden E, Carretero G, et al. Survival of classic and biological systemic drugs in psoriasis: results of the BIOBADADERM registry and critical analysis. J Eur Acad Dermatol Venereol. 2016;30(11):1942–50.PubMedCrossRef
160.
Shalom G, Zisman D, Harman-Boehm I, et al. Factors associated with drug survival of methotrexate and acitretin in patients with psoriasis. Acta Derm Venereol. 2015;95(8):973–7.PubMedCrossRef
161.
Papadavid E, Rompoti N, Theodoropoulos K, Kokkalis G, Rigopoulos D. Real-world data on the efficacy and safety of apremilast in patients with moderate-to-severe plaque psoriasis. J Eur Acad Dermatol Venereol. 2018;32(7):1173–9.PubMedCrossRef
162.
Lee EB, Amin M, Wu JJ. Drug survival of apremilast in patients treated for psoriasis in a real-world setting. J Am Acad Dermatol. 2018;79(4):760–1.PubMedCrossRef
163.
Santos-Juanes J, Velasco L, Munguía-Calzada P, Lozano A, Gómez-Díez S. Comment on “Drug survival of apremilast for psoriasis in a real-world setting”. J Am Acad Dermatol. 2018;79(4):e83–e8484.PubMedCrossRef
164.
Vujic I, Herman R, Sanlorenzo M, et al. Apremilast in psoriasis—a prospective real-world study. J Eur Acad Dermatol Venereol. 2018;32(2):254–9.PubMedCrossRef
165.
Vujic I, Herman R, Sanlorenzo M, et al. Apremilast in psoriasis-a prospective real-world study. J Invest Dermatol. 2017;137(10):S195 (abstract 014).CrossRef
166.
Otero ME, van den Reek JM, Seyger MM, van de Kerkhof PC, Kievit W, de Jong EM. Determinants for drug survival of methotrexate in patients with psoriasis, split according to different reasons for discontinuation: results of the prospective MTX-CAPTURE. Br J Dermatol. 2017;177(2):497–504.PubMedCrossRef
167.
Maul JT, Djamei V, Kolios AGA, et al. Efficacy and survival of systemic psoriasis treatments: an analysis of the Swiss Registry SDNTT. Dermatology. 2016;232(6):640–7.PubMedCrossRef
168.
Ismail N, Collins P, Rogers S, Kirby B, Lally A. Drug survival of fumaric acid esters for psoriasis: a retrospective study. Br J Dermatol. 2014;171(2):397–402.PubMedCrossRef
169.
Damiani G, Cazzaniga S, Naldi L, PsoReal Study Group. Use of fumaric acid derivatives (FADs) in Italian reference centres for psoriasis. G Ital Dermatol Venereol. 2019. https://​doi.​org/​10.​23736/​S0392-0488.​18.​06032-7.​
170.
Lee EB, Amin M, Wu JJ. Reply to: “Comment on ‘Drug survival of apremilast for psoriasis in a real-world setting’”. J Am Acad Dermatol. 2018;79(4):e85.PubMedCrossRef
171.
172.
Au S, Levin AA, Gottlieb AB. Psoriasis drug failure rates of biologics compared to conventional systemic therapies. J Invest Dermatol. 2014;134(Suppl 1):S9 (abstract 047).
173.
Menter A, Gelfand JM, Connor C, et al. Joint American Academy of Dermatology–National Psoriasis Foundation guidelines of care for the management of psoriasis with systemic non-biological therapies. J Am Acad Dermatol. 2020;82(6):1445–86.
Metadata
Title
Long-term Safety of Oral Systemic Therapies for Psoriasis: A Comprehensive Review of the Literature
Authors
Deepak M. W. Balak
Sascha Gerdes
Aurora Parodi
Laura Salgado-Boquete
Publication date
01-08-2020
Publisher
Springer Healthcare
Published in
Dermatology and Therapy / Issue 4/2020
Print ISSN: 2193-8210
Electronic ISSN: 2190-9172
DOI
https://doi.org/10.1007/s13555-020-00409-4

Other articles of this Issue 4/2020

Dermatology and Therapy 4/2020 Go to the issue

Original Research

Intralesional Methotrexate for the Treatment of Advanced Keratinocytic Tumors: A Multi-Center Retrospective Study

Case Report

Clinical, Dermoscopic and In-Vivo Reflectance Confocal Microscopy Evaluation of a Case of Graham Little-Piccardi-Lassueur Syndrome Successfully Treated with Narrowband-UVB Phototherapy

Case Report

Toripalimab-Induced Dermatomyositis in a Patient with Metastatic Melanoma

Case Report

Novel Coronavirus Disease (COVID-19) and Biologic Therapy for Psoriasis: Successful Recovery in Two Patients After Infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

Case Report

Successful Treatment of Refractory Candidal Granuloma by Itraconazole and Terbinafine in Combination with Hyperthermia and Cryotherapy

Case Report

Risankizumab-Aggravated Crusted Scabies in a Patient with Down Syndrome
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits