Safety Assessment of Conventional and Biological Systemic Therapy in Older Adults with Psoriasis, a Real-world Multicentre Cohort Study.

Optimal selection of systemic therapy in older adults with psoriasis can be challenging, due to sparse evidence-based guidance. This multicentre retrospective study investigated the safety of systemic therapy with causality assessment in a real-world cohort of older adults (≥ 65 years) with psoriasis. Data from 6 hospitals on (serious) adverse events were collected, causality assessment performed and incidence rate ratios calculated. Potential predictors for adverse events-occurrence were studied using multivariable logistic regression analysis. In total, 117 patients with 176 treatment episodes and 390 patient-years were included, comprising 115 (65.3%) and 61 (34.7%) treatment episodes with conventional systemic therapy and biologics/apremilast, respectively. After causality assessment, 232 of 319 (72.7%) adverse events remained and were analysed further, including 12 serious adverse events. No significant differences in incidence rate ratios were found between the systemic treatment types. In regression analysis, increasing age was associated with causality assessed adverse events-occurrence (odds ratio 1.195; p=0.022). Comorbidity, polypharmacy, and treatment type were not associated with causality assessed adverse events-occurrence. In conclusion, increasing age was associated with a higher causality assessed adverse events-occurrence. Causality assessed serious adverse events were rare, reversible and/or manageable in clinical practice. In conclusion, the safety profile of systemic antipsoriatic therapy within this population is reassuring.

Impact of High Age and Comorbidity on Management Decisions and Adherence to Guidelines in Patients with Keratinocyte Skin Cancer.

Appropriate medical decision-making in patients with keratinocyte skin cancer (KSC) can be challenging, especially in those with a limited life expectancy (LEx). Treatment should be beneficial for the individual patient, the risk of both over- and under-treatment should be carefully considered, and deviation from guideline recommendations may be necessary. In this study retrospective analysis was performed to determine the influence of age and comorbidity, both factors strongly related to limited LEx, on KSC management in daily practice. After analysis of 401 patients it was found that management in patients with KSC is not influenced, or is only minimally influenced, by high age and comorbidity. Better integration of aspects related to a limited LEx in KSC management might optimize care and prevent overtreatment. Future research on the general prognostication, prediction of the patient burden caused by tumour and treatment, and time-to-benefit in KSC management is strongly recommended.

Prospective comparison of three guideline development methods for treatment of actinic keratosis.

OBJECTIVE: To compare three methods of guideline development, to see whether using alternative evidence-based methods resulted in variation of recommendations for treating actinic keratosis. METHODS: Method 1 followed a standard multiple session evidence-based approach with a working group. In method 2 recommendations were formulated by a working group during a 2-day conference. Method 3 used one epidemiologist to summarise the evidence and one dermatologist to make clinical recommendations afterwards. Graded recommendations and levels of evidence were compared per therapy across three draft guidelines. The primary outcome was the extent of accordance or discordance. Secondary outcomes were total costs and time period necessary to make a draft guideline. RESULTS: Therapeutic recommendations and levels of evidence differed in some occasions. However, intraclass correlations between levels of evidence were significant (method 1 vs 2: p = 0.003; method 1 vs 3: p < 0.001). Regarding recommendation variation method 1 and method 2 correlated significant at 0.755 (p = 0.001). Method 1 versus 3 and method 2 versus 3 also showed significant, but lower, correlation coefficients (respectively, 0.493 (p = 0.026) and 0.673 (p = 0.007)). Method 3 was the cheapest and quickest (24,770 euro and 4 months) and method 1 was the most expensive and slowest method (€48,100 euro and 14 months). CONCLUSIONS: The value of a guideline using alternative evidence-based methods seems to at least equal that of a guideline composed in multiple sessions, that is, for topics with a monodisciplinary character and a relatively small number of conducted trials. In addition, the presented alternatives were more time- and cost-efficient.

Off-label use of azathioprine in dermatology: a systematic review.

OBJECTIVE: To summarize evidence regarding the effectiveness, efficacy, and safety of off-label azathioprine use in dermatology. DATA SOURCES: We searched the MEDLINE (1950-2009), EMBASE (1980-2009), and CENTRAL (1996-2009) databases on October 9, 2009. The main search terms were azathioprine and its synonyms. No restrictions were imposed regarding publication date. Only articles in English, French, German, or Dutch were included. STUDY SELECTION: Randomized controlled trials, cohorts, and case series concerning the use of azathioprine in an off-label dermatologic setting were independently assessed for eligibility by 2 coauthors. The search retrieved 3870 articles, and 148 articles were selected for detailed review. DATA EXTRACTION: Forty-three articles matching the inclusion and exclusion criteria were reviewed for methodologic quality by 2 reviewers independently, including an evaluation of components associated with biased estimates of treatment effect. DATA SYNTHESIS: High-quality evidence (level A) was found for a moderate therapeutic effect in severe atopic dermatitis. Evidence of moderate quality (level B) was found for efficacy in parthenium dermatitis (an airborne plant allergen contact dermatitis), bullous pemphigoid, chronic actinic dermatitis, and leprosy type 1 reaction. Furthermore, favorable therapeutic effects existed for erythema multiforme, lichen planus, and pityriasis rubra pilaris, although the quality of evidence was low (level C). CONCLUSIONS: A strong clinical recommendation was given for azathioprine in atopic dermatitis. Conclusions regarding safety in an off-label setting could not be reached because of scarce and incomplete data (level C evidence). Long-term registries and prospective studies could add to the existing evidence and provide legal support for off-label drug use in dermatology.