Significant delay in the introduction of systemic treatment of moderate to severe psoriasis: a prospective multicentre observational study in outpatients from hospital dermatology departments in France.

BACKGROUND: There is a low rate of systemic treatment usage in moderate to severe psoriasis. OBJECTIVES: The primary objective of the present study was to assess the time period between lack of control of moderate to severe psoriasis with topical treatment or phototherapy as perceived by patients and the medical decision to introduce a systemic treatment. METHODS: This was a prospective multicentre study, which included patients with moderate to severe psoriasis. A standardized questionnaire was completed by physicians and patients at the time the decision was taken to introduce a systemic treatment. The primary outcome was the duration of uncontrolled psoriasis, as estimated by the patient, prior to the introduction of systemic treatment. Factors associated with a delay in systemic treatment defined as > 2 years of uncontrolled psoriasis were assessed. The agreement between patients and physicians on the duration of uncontrolled psoriasis was estimated. RESULTS: The study included 142 patients. The mean age was 48 years, the mean Psoriasis Area and Severity index (PASI) was 18·5 and the mean Dermatology Life Quality Index (DLQI) was 12. The median duration of uncontrolled psoriasis estimated by patients and physicians was 3 years and 2 years, respectively. Factors associated with a delay in the introduction of systemic treatment as assessed by patients were fewer than three physician visits since psoriasis was uncontrolled [odds ratio (OR) 3·05; 95% confidence interval (CI) 1·29-7·21], Hospital Anxiety and Depression (HAD) scale < 10 (OR 2·83; 95% CI 1·19-6·71), continuous psoriasis evolution (OR 2·67; 95% CI 1·12-6·42), low consumption of topical treatment (OR 2·35; 95% CI 1·03-5·34). CONCLUSIONS: There is a significant delay in the introduction of systemic treatment in moderate to severe psoriasis. Patients with low level anxiety and limited use of healthcare resources appear to be at higher risk of experiencing long delays.

Methotrexate in psoriasis: a systematic review of treatment modalities, incidence, risk factors and monitoring of liver toxicity.

BACKGROUND/AIM: To define practical use and to specify the ideal method for monitoring the liver toxicity of MTX in the management of psoriasis. OBJECTIVE: To systematically review the literature regarding treatment modalities with methotrexate (MTX) in psoriasis, risk of MTX-mediated liver fibrosis and monitoring of hepatic toxicity. METHODS: A systematic literature search was carried out in Medline, Embase and Cochrane Library databases from 1980 to 2010 searching for randomized controlled trials and observational studies on methods of administering MTX in psoriasis and risk factors and assessment of liver toxicity. We limited the literature search to articles on human subjects over 19 years of age, articles in English or French on psoriasis and articles including psoriatic arthritis and original data. RESULTS: Among 949 references identified, 23 published studies were included. There were no studies focusing directly on the question of MTX treatment modalities. Treatment outcome appears to be dose dependent. A single study in rheumatoid arthritis showed the slightly superior efficacy of subcutaneous administration vs. oral dosing with a similar safety profile. Combination with folic acid may decrease the efficacy of MTX while improving tolerability. The extreme variability of the incidence of hepatic fibrosis in the literature does not allow the risk of hepatic fibrosis to be quantified. Type 2 diabetes and obesity, were associated with a significant increased risk of liver fibrosis. Hepatitis B and C and alcohol consumption were associated with a modest and non-significant increased risk of liver fibrosis. Procollagen III for detection of hepatic fibrosis dosing was the most extensively validated method to monitor liver fibrosis showing a sensitivity of 77.3% and a specificity of 91.5%. The Positive Predictive Value and Negative Predictive Value fluctuated depending on the prevalence of hepatic fibrosis. The sensitivities of the FibroTest and the fibroscan were of 83 and 50%, respectively, with specific features amounting to 61 and 88% respectively. CONCLUSIONS: Based on expert experience, the starting dose of MTX is between 5 and 10 mg/week for the first week. Fast dose escalation is recommended in order to obtain a therapeutic target dose of 15-25 mg/week. The maximum recommended dose is 25 mg/week. A folic acid supplement is necessary. The initiation of treatment by oral administration is preferred. In cases where inadequate response is obtained or in the event of poor gastrointestinal tolerance, subcutaneous dosing can be proposed at the same dose. Published data do not confirm the incidence of hepatic fibrosis. Type 2 diabetes and obesity appear to be significant risk factors in fibrosis. A combination of FibroTests and fibroscans together with measurement of the type III serum procollagen aminopeptide seem to be ideal method for monitoring liver toxicity.

Efficacy and safety of oral retinoids in different psoriasis subtypes: a systematic literature review.

BACKGROUND: There is limited evidence regarding the efficacy and safety of retinoids in different psoriasis subtypes. OBJECTIVE: To systematically review the available literature on: (i) modalities of administration and prescription of oral retinoids as single agent or combined therapy for the treatment of plaque-type psoriasis (PV), nail psoriasis and localized and generalized pustular psoriasis : initial and optimal dosage; (ii) skeletal toxicity of retinoid for the treatment of psoriasis. METHODS: A systematic literature search was carried out in MEDLINE, EMBASE, and Cochrane Library databases from 1975 to 2010 searching for randomized controlled trials and observational studies evaluating 1) various dosages of retinoid in psoriasis and 2) skeletal toxicity of retinoid in psoriasis. Articles were limited to human subjects and English/French languages. RESULTS: Efficacy of retinoids in psoriasis. Among 1348 identified references, 44 published studies were included. Starting daily dosages between 10 and 25 mg and stepwise escalation were associated with higher clinical efficacy and lower incidence of adverse events in comparison with higher doses and regimens rapidly reaching optimal dose. Retinoids as single agent therapy appeared to show limited efficacy in PV, while the good clinical efficacy reported in pustular forms should be cautiously considered, given the spontaneously remitting course of the disease. Combining retinoids with phototherapy appeared to be highly effective in patients with PV. Potential skeletal toxicity of retinoids. 15 published studies out of 105 identified references were included. There is no strong evidence of an increased risk of skeletal abnormalities in psoriasis patients treated with retinoids. CONCLUSION: Acitretin appears to provide better efficacy in pustular psoriasis than in PV as a single agent treatment. There is no evidence for skeletal toxicity of retinoids in the setting of psoriasis, and accordingly monitoring this risk through X-ray is not warranted.