Systemic Therapies For Psoriasis Research Articles

Advances in systemic therapy for psoriasis.

Severe cases of psoriasis and psoriasis arthritis require systemic treatment. Although a number of established drugs are in clinical use, there is a need for new compounds with an improved risk-benefit ratio with a major emphasis on long-term safety. Furthermore, patients with moderate psoriasis ask for systemic drugs to make therapy easier and to avoid excessive local treatments. This article aims to give a brief overview about new drugs or groups of compounds together with an evaluation of their present status in the treatment of psoriasis and their future role with particular respect to efficacy, tolerability, safety and usability.

Management of Psoriasis

Oral synthetic retinoids have been established as effective systemic therapy for psoriasis since their introduction for clinical use in the 1970s; a compound for topical use, tazarotene has been recently marketed. Despite the demonstrated clinical success of retinoid therapy in psoriasis, its mechanism of action has not been fully elucidated, and investigators are confronted with two paradoxes. One is that the binding of retinoids to nuclear retinoic acid receptors (RARs) does not match their therapeutic efficacy: acitretin activates the three receptor subtypes, RAR-alpha, -beta and -gamma, without measurable receptor binding, whereas tazarotene preferentially binds to and activates RAR-beta and -gamma in preference to RAR-alpha. The other is that there is already increased formation of retinoic acid in the psoriatic lesion. Answering these questions should result in better use of these drugs in the treatment of psoriasis. Oral administration of acitretin remains one of the first therapeutic choices for severe psoriasis, particularly in association with ultraviolet light therapy, of which it may decrease the carcinogenic risk. Topical tazarotene is suitable for moderate plaque psoriasis. Its efficacy and tolerability can be enhanced by the addition of topical corticosteroids; its irritative potential is counterbalanced by a sustained therapeutic effect after the treatment is stopped.

Acitretin combination therapy

Systemic therapies used in psoriasis such as methotrexate, PUVA, cyclosporine, and acitretin often have side effects that limit their usefulness. Combination therapy, an effective strategy for treating psoriasis, allows use of lower doses of medications to achieve superior therapeutic results with fewer side effects. Acitretin is one of the most popular drugs used in combination with other systemic therapies for psoriasis. Details of the regimens used and results obtained from combining acitretin with PUVA, cyclosporine, and methotrexate are discussed. (J Am Acad Dermatol 1999;41:S18-21.)

Systemic sequential therapy of psoriasis: A new paradigm for improved therapeutic results

Sequential therapy is a treatment strategy involving the use of specific therapeutic agents in a deliberate sequence to optimize the therapeutic outcome. The rationale for this strategy in psoriasis is that it is a chronic disease requiring long-term maintenance therapy as well as quick relief of symptoms and that some therapies available for psoriasis are better suited for rapid clearance while others are more appropriate for long-term maintenance. Sequential therapy involves 3 main steps: (1) the clearing, or “quick-fix” phase; (2) the transitional phase; and (3) the maintenance phase. In the example of sequential systemic therapy described in this article, an acute exacerbation of psoriasis is brought under control promptly with the use of cyclosporine at maximum dermatologic dose (5 mg/kg daily). After 1 month, the transitional phase is initiated with the gradual introduction of acitretin as a maintenance agent. Once the maximum tolerated dose of acitretin has been established, cyclosporine is gradually tapered and acitretin is continued for long-term maintenance with phototherapy (UVB or PUVA) added for improved control if needed. The author proposes sequential therapy with cyclosporine and acitretin as a viable option for patients with psoriasis who require systemic therapy and desire an alternative to methotrexate. (J Am Acad Dermatol 1999;41: S25-8.)

Retinoids and psoriasis: Novel issues in retinoid pharmacology and implications for psoriasis treatment

Oral synthetic retinoids have been established as effective systemic therapy for psoriasis since their introduction for clinical use in the 1970s. Acitretin, the free acid of etretinate and its active metabolite, has replaced etretinate as the retinoid of choice for treating psoriasis because of its more favorable pharmacokinetic profile. Despite the demonstrated clinical success of retinoid therapy in psoriasis and other proliferative skin disorders, their mechanism of action has not been fully elucidated. Altered vitamin A metabolism, characterized by an increase in the formation of retinoic acid, has been demonstrated in psoriatic lesions and is potentially influenced by cytokines such as interferon gamma, which is present in high levels in these lesions. Synthetic retinoids such as acitretin may interfere with such cytokine-induced alterations. Studies on nuclear retinoic acid receptors have shown that acitretin activates all 3 receptor subtypes (RAR-alpha, -beta, and -gamma) without measurable receptor binding; this paradox remains unexplained. Further studies on nuclear receptor binding and activity, including possible receptor crosstalk with vitamin D nuclear receptors, promise to enhance understanding of the usefulness of retinoids in treatment of psoriasis. (J Am Acad Dermatol 1999;41:S2-6.)

Systemic psoriasis therapy has future potential

Systemic psoriasis therapy has future potential

Systemic Drug Therapy for Psoriasis

Guzzo and colleagues 1 present, in this issue ofArchives, the results of a phase I and II study of piritrexim, a nonclassical folate antagonist, for the reatment of severe psoriasis. This open study demonstrated a dose-dependent improvement in psoriasis patients receiving at least 100 mg/d for 5 consecutive days every 2 weeks. Reversible hepatotoxicity or leukopenia were noted in several patients. The hepatotoxicity was surprising in view of the rarity of this adverse effect in the oncology literature. See also p 511. Using the piritrexim article as a springboard for discussion, this editorial briefly addresses issues confronting dermatologists who prescribe systemic chemotherapy for patients with severe psoriasis. The risks and benefits of methotrexate, cyclosporine, and hydroxyurea in the treatment of psoriasis are discussed. Although retinoids and psoralen plus UV-A (PUVA) are beyond the scope of this discussion, the principles that follow can be applied to these therapies as well.

Systemic drug therapy for psoriasis. The most critical issues

Systemic drug therapy for psoriasis. The most critical issues

Systemic psoriasis therapies should be alternated

Systemic psoriasis therapies should be alternated

Evaluation of the role of sulphasalazine in the treatment of moderate to severe psoriasis

The efficacy of sulphasalazine in the treatment of psoriasis was assessed by a double-blind trial performed on 17 patients. Treatment with sulphasalazine for 4 weeks caused a significant improvement in total body surface area of psoriasis and amount of scale, but produced no significant reduction in erythema or thickness of the plaques. Acetylator status was performed on patients drawn from both the double-blind trial and a preliminary open trial to assess if therapeutic response might be related to this factor. There was no correlation between overall response of psoriasls to sulphasalazine and the acetylator status of the patient. It is concluded that sulphasalazine is a safe, cheap and effective systemic therapy for psoriasis. Although side-effects are relatively common, they occur early and are reversible on discontinuation of the drug.

Systemic retinoid therapy for psoriasis

Retinoids are potent therapuetic agents that have been found to be effective in a variety of skin diseases. They are of benefit in various forms of severe psoriasis. With severe plaque psoriasis, they are used most effectively in combination with other forms of therapy, such as phototherapy. With generalized pustular psoriasis, they are effective monotherapy and are frequently helpful for the control of exfoliative psoriasis. A variety of new retinoid analogs have been studied in clinical investigations. This article discusses important aspects of the use of etretinate, isotretinoin, acitretin, and arotinoid ethyl ester in the treatment of severe forms of psoriasis.

Systemic Therapies for Psoriasis: recent clinical trials

Systemic Therapies for Psoriasis: recent clinical trials

Cost-effectiveness of PUVA

Five years ago a new form of systemic therapy for psoriasis was introduced. 1 The treatment combines the oral injestion of methoxsalen followed by increasing light (long-wave ultraviolet light [UVA]) given in special phototherapy boxes in established centers. This outpatient form of therapy has proved highly effective in two large cooperative studies 2,3 in the United States and also has been confirmed as standard therapy worldwide. The short-term side effects have been minimal and acceptable. Long-term side effects are yet to be determined, but one study 4 has suggested increased incidence of skin cancer, especially squamous cell carcinoma, but other studies 5,6 have argued that patients with severe psoriasis may have increased incidence of skin cancer because of exposure to other carcinogens such as x-ray, ultraviolet light in the sunlight range (UVB) for Goeckerman therapy, and other chemotherapeutic drugs. PUVA may increase the risk of skin cancer but no more than

Cost-effectiveness of PUVA

Five years ago a new form of systemic therapy for psoriasis was introduced.¹The treatment combines the oral injestion of methoxsalen followed by increasing light (long-wave ultraviolet light [UVA]) given in special phototherapy boxes in established centers. This outpatient form of therapy has proved highly effective in two large cooperative studies^2,3in the United States and also has been confirmed as standard therapy worldwide. The short-term side effects have been minimal and acceptable. Long-term side effects are yet to be determined, but one study⁴has suggested increased incidence of skin cancer, especially squamous cell carcinoma, but other studies^5,6have argued that patients with severe psoriasis may have increased incidence of skin cancer because of exposure to other carcinogens such as x-ray, ultraviolet light in the sunlight range (UVB) for Goeckerman therapy, and other chemotherapeutic drugs. PUVA may increase the risk of skin cancer but no more than

Aspects of the relationship between psychiatric status, sleep, nocturnal motility and nutrition

To review the Tayside home phototherapy service, including numbers of patients treated, diagnoses and outcomes, side-effects and safety, cost-effectiveness and absolute costs. To consider why home or outpatient phototherapy is not available to all patients who might benefit and how this could be addressed.Observational and cost analysis.Analysis of the Tayside home phototherapy database 1998 and 2011, home phototherapy patient questionnaires, outcome data, costs and a comparison with outpatient phototherapy. Review of literature and current national guidelines for phototherapy, traditional systemic and biologic therapies for psoriasis.298 courses of home narrowband UVB (NB-UVB) phototherapy were undertaken by 212 patients between 1998 and 2011, five courses in 1998 increasing to 36 in 2011. The main diagnoses treated were psoriasis (72%), atopic dermatitis (8%), and desensitization of photodermatosis (7%). For psoriasis, 74.5% achieved clearance or minimal residual activity in a median of 30 exposures (range 10–60). The estimated costs to the hospital ranged from £229 to £314 per course (£307 to £422 per effective course for psoriasis), compared with £114 for out-patient therapy (£149 per effective course for psoriasis). The total cost to society (hospital and patient costs) is around £410 per course, compared to an estimated £550 for outpatient therapy for this group of patients. Treatment was well tolerated, erythema rates were similar to outpatient therapy, there were no complaints and the vast majority would choose home over outpatient phototherapy if required in the future.Hospital supervised home phototherapy appears as safe and effective as outpatient therapy and provides equality of access for patients who cannot attend for outpatient therapy. These patients may otherwise be inadequately treated or given more costly and higher risk systemic therapies, particularly for psoriasis. Commissioners and clinicians involved in dermatology services should provide accessible phototherapy for all patients who might benefit, utilizing home phototherapy where outpatient access is not possible.