Acitretin: Optimal dosing strategies

doi:10.1016/S0190-9622(99)70360-9

Journal of the American Academy of Dermatology

Volume 41, Issue 3, Supplement, September 1999, Pages S13-S17

https://doi.org/10.1016/S0190-9622(99)70360-9 Get rights and content

Abstract

Acitretin is an oral synthetic retinoid effective in the treatment of psoriasis. As monotherapy, acitretin has been shown to be most effective in treating pustular and erythrodermic types of the disease. Monotherapy with acitretin for plaque-type psoriasis is often less successful; however, its use in combination with other therapies is highly effective in treating this form of the disease. Dose-response studies have established the effective dose range of acitretin as well as the dose-dependence of its side effects. Because both efficacy and side effects can vary substantially among individual patients, proper dosing of acitretin requires a balance between optimizing response and minimizing toxicity for each patient. Optimal dosing for individual patients may be achieved through a dose-escalation strategy involving initiation of therapy at low doses (10 to 25 mg/day) and, if necessary, gradually increasing the dose as tolerated until optimal response is achieved. (J Am Acad Dermatol 1999;41:S13-17.)

Section snippets

ACITRETIN MONOTHERAPY

Initial research on the efficacy of acitretin in treating psoriasis involved use of acitretin as a single agent compared with either placebo or etretinate. In 1989, Kragballe et al⁵ reported results from 127 patients treated with acitretin compared with 41 patients treated with etretinate. All patients were started on acitretin or etretinate at a dose of 40 mg/day for the first 4 weeks. The dose was then adjusted for each patient to maximize improvement of the lesions while minimizing side

DOSE-RANGING STUDIES

Additional studies on acitretin monotherapy for psoriasis include dose-ranging studies designed to establish optimal dose as well as the dose-dependence of side effects. In one dose-ranging study by Lassus et al,¹⁰ patients were randomized to a daily dose of 10, 25, or 50 mg of acitretin. After 8 weeks, a dose-response trend was observed, with patients averaging a reduction in PASI score of 61%, 79%, and 86%, respectively, compared with a 30% average reduction in PASI score in patients

DOSE ESCALATION

Dose-ranging studies have clearly established that, as with other retinoids, both efficacy and toxicity of acitretin increase significantly at higher doses. Clinical experience has also shown that both therapeutic and toxic responses to the drug vary greatly among individual patients. Therefore, a single “correct” dose cannot be recommended.

An effective dosing strategy broadly applicable for establishing optimal dose in balancing efficacy and toxicity in an individual, however, can be

CONCLUSION

Studies on dosing strategies for acitretin as a single agent in the treatment of psoriasis have established that higher doses of acitretin have more rapid effects and are more likely to result in greater improvement in psoriatic lesions. They have also demonstrated that higher doses are associated with a higher incidence and severity of side effects and that important toxicities including mucocutaneous side effects, hepatotoxicity, and alterations in serum lipid profile are dose-dependent.

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Cited by (53)

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Citation Excerpt :
Acitretin is less beneficial than other common systemic psoriasis medications, although head-to-head comparison studies are lacking. The effects of acitretin are dose-dependent, and a number of different dosing schedules have been used.151-158 In one study, 23% of patients treated with acitretin 50 mg/d achieved PASI 75 after 8 weeks of therapy, with some patients experiencing complete clearance of skin disease.159
Psoriasis is a chronic inflammatory disease involving multiple organ systems and affecting approximately 2% of the world's population. In this guideline, we focus the discussion on systemic, nonbiologic medications for the treatment of this disease. We provide detailed discussion of efficacy and safety for the most commonly used medications, including methotrexate, cyclosporine, and acitretin, and provide recommendations to assist prescribers in initiating and managing patients on these treatments. Additionally, we discuss newer therapies, including tofacitinib and apremilast, and briefly touch on a number of other medications, including fumaric acid esters (used outside the United States) and therapies that are no longer widely used for the treatment of psoriasis (ie, hydroxyurea, leflunomide, mycophenolate mofetil, thioguanine, and tacrolimus).
Systemic Retinoids
2020, Comprehensive Dermatologic Drug Therapy, Fourth Edition
Retinoids are derivatives of vitamin A and have a long history of use in dermatology, as systemic and topical agents, in the treatment of acne, psoriasis, cutaneous T cell lymphoma, and disorders of keratinization. More recently, these drugs have been increasingly used for chemoprevention of skin cancer. Despite the risk of teratogenicity, retinoids are valuable medications and it is important for the dermatologist to be comfortable with their use.
Acitretin
2016, Therapy for Severe Psoriasis
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Citation Excerpt :
Dose-response studies have established the dose dependence of its side effects. It is recommended to initiate the therapy at low doses (10-25 mg/day) and, if necessary, gradually increase the dose until optimal effect is achieved.72 Acitretin may rarely cause intracranial hypertension and papilledema.70
The use of many drugs in dermatologic diseases may cause ocular side effects. Some may regress after discontinuation of the therapy, but others persist or progress even after the cessation of treatment. This review presents four groups of commonly prescribed drugs—antimalarial medicines, glucocorticoids, retinoids, and psoralens + ultraviolet A (UVA) therapy—and discusses their possible ocular side effects.
The most significant complication of antimalarial drugs is retinopathy with the risk of permanent visual impairment. There are different recommendations for screening for this drug-related retinopathy. The most important ocular manifestations of steroid management are irreversible optic nerve damage in “steroid responders” (steroid glaucoma) and cataract. Some other side effects may disappear after discontinuation of the therapy. Retinoid-induced ocular side effects include ocular surface disease as well as retinal dysfunction. It is recommended to modify the therapy when night blindness occurs or after the decrease of color vision. Protective eyewear is sufficient to avoid ocular surface problems during psoralen + UVA therapy.
The knowledge of screening schemes and closer cooperation between physicians may decrease the risk of serious or irreversible ocular side effects.
Guidelines for the use of acitretin in psoriasis
2013, Actas Dermo-Sifiliograficas
La fototerapia y los tratamientos sistémicos clásicos (metotrexato, acitetrina, ciclosporina), junto con las denominadas terapias biológicas (etanercept, infliximab, adalimumab, ustekinumab), permiten al dermatólogo disponer de un arsenal terapéutico amplio que aumenta las posibilidades de control de pacientes con psoriasis grave y/o extensa. La acitretina sigue siendo de gran utilidad tanto en monoterapia como combinada con otros fármacos sistémicos (clásicos o «biológicos»), o en terapia secuencial. Se distingue por no ser inmunosupresor directo y mantener respuestas a muy largo plazo, lo que le confiere un papel relevante en el tratamiento de la psoriasis, que no siempre ha sido reconocido en las diversas guías terapéuticas de esta enfermedad.
Se presenta una guía de uso de acitretina consensuada por los miembros del Grupo de Psoriasis de la Academia Española de Dermatología y Venereología, en la que se exponen de forma detallada aspectos de la farmacología del fármaco, sus indicaciones y contraindicaciones, su eficacia antipsoriásica, los efectos adversos asociados al fármaco, las acciones a tener en cuenta para aumentar la seguridad de su uso, y se propone diversas estrategias terapéuticas de aplicación en la práctica clínica habitual. El objetivo global es facilitar los criterios de indicación y manejo de la acitretina en pacientes con psoriasis.
Phototherapy, classic systemic treatments (methotrexate, acitretin, and ciclosporin), and biologic agents (etanercept, infliximab, adalimumab, and ustekinumab) constitute a broad therapeutic arsenal that increases the likelihood of achieving control of severe and extensive disease in patients with psoriasis. Acitretin continues to be a very valuable tool in both monotherapy, in which it is combined with other systemic treatments (classic or biologic), and in sequential therapy. Thanks to its lack of a direct immunosuppressive effect and its ability to achieve a long-term response, acitretin has an important role in the treatment of psoriasis, although this has not always been acknowledged in relevant treatment guidelines.
We present consensus guidelines for the use of acitretin in psoriasis drawn up by the Psoriasis Group of the Spanish Academy of Dermatology and Venereology. These guidelines provide a detailed account of acitretin, including pharmacological properties, indications and contraindications, adverse effects, and factors that should be taken into account to enhance the safe use of this drug. They also propose treatment strategies for use in routine clinical practice. The overall aim of these guidelines is to define the criteria for the use and management of acetretin in psoriasis.
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^☆: From MedaPhase, Inc, Atlanta.

^☆☆: This manuscript is based on a presentation given at the 5th European Congress on Psoriasis/7th International Psoriasis Symposium in Milan, Italy on September 2, 1998, with support from Roche Laboratories, Inc., Nutley, NJ.

^★: Reprint requests: Mark R. Ling, MD, PhD, MedaPhase, Inc., 393 Mill Creek Bend NE, Atlanta, GA 30307.

^★★: 0190-9622/99/$8.00 + 0 16/0/100481

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Abstract

Section snippets

ACITRETIN MONOTHERAPY

DOSE-RANGING STUDIES

DOSE ESCALATION

CONCLUSION

Dermatol Clin

J Am Acad Dermatol

J Am Acad Dermatol

J Am Acad Dermatol

J Am Acad Dermatol