Quantitative Evaluation of Biologic Therapy Options for Psoriasis: A Systematic Review and Network Meta-Analysis.

Multiple biologic treatments are licensed for psoriasis. The lack of head-to-head randomized controlled trials makes choosing between them difficult for patients, clinicians, and guideline developers. To establish their relative efficacy and tolerability, we searched MEDLINE, PubMed, Embase, and Cochrane for randomized controlled trials of licensed biologic treatments for skin psoriasis. We performed a network meta-analysis to identify direct and indirect evidence comparing biologics with one another, methotrexate, or placebo. We combined this with hierarchical cluster analysis to consider multiple outcomes related to efficacy and tolerability in combination for each treatment. Study quality, heterogeneity, and inconsistency were evaluated. Direct comparisons from 41 randomized controlled trials (20,561 participants) were included. All included biologics were efficacious compared with placebo or methotrexate at 3-4 months. Overall, cluster analysis showed adalimumab, secukinumab, and ustekinumab were comparable in terms of high efficacy and tolerability. Ixekizumab and infliximab were differentiated by very high efficacy but poorer tolerability. The lack of longer term controlled data limited our analysis to short-term outcomes. Trial performance may not equate to real-world performance, and so results need to be considered alongside real-world, long-term safety and effectiveness data. These data suggest that it is possible to discriminate between biologics to inform clinical practice and decision making (PROSPERO 2015:CRD42015017538).

Risk of Serious Infections in Patients with Psoriasis on Biologic Therapies: A Systematic Review and Meta-Analysis.

A comprehensive evaluation of the risk of serious infections in biologic therapies for psoriasis is lacking. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) and prospective cohort studies reporting serious infections in people taking any licensed biologic therapy for psoriasis compared with those taking placebo, nonbiologic therapy, or other biologic therapies. The quality of the studies was assessed using Grading of Recommendations Assessment, Development and Evaluation criteria. No significant heterogeneity was detected in data from 32 RCTs (n = 13,359 participants) and one cohort study (n = 4,993 participants). In adults, low- to very-low-quality RCT data showed no significant difference between any biologic therapy and placebo at weeks 12-16 (overall pooled Peto odds ratio = 0.71, 95% confidence interval = 0.36-1.41) and weeks 20-30 (odds ratio = 2.27, 95% confidence interval = 0.45-11.49). No significant differences were found in any of the other comparisons in underpowered RCT data. Prospective cohort study data of low quality suggests that only adalimumab (adjusted hazard ratio [adjHR] = 2.52, 95% confidence interval = 1.47-4.32) was associated with a significantly higher risk of serious infection compared with retinoid and/or phototherapy in adults. No association between biologic therapies and serious infections in patients with psoriasis who were eligible for RCTs was detected. Further observational studies are needed to inform the uncertainty around this risk in the real world.

Biological therapies for the treatment of severe psoriasis in patients with previous exposure to biological therapy: a cost-effectiveness analysis.

BACKGROUND: Biologic therapies have revolutionised the care of patients with psoriasis, although they come at significant extra cost. Guidance on their use in the UK National Health Service (NHS) has so far focused on patients who are "biologic naive", yet a minority of patients have poor response and require further treatment. OBJECTIVES: To assess the potential cost effectiveness of sequential biologic therapies in patients with psoriasis who have been exposed to previous biologic therapy. METHODS: A two-part model with a 10-year time horizon was built to model an initial 13.5-week "trial" phase and a longer-term "treatment" period with annual Markov cycles. Psoriasis Area and Severity Index (PASI) response rates from subgroup analyses of three randomised placebo-controlled trials evaluating biologic agents were considered. A meta-analysis of these data provided probabilities of achieving PASI response (50/75/90) in the short term, and published evidence and assumptions were used to predict outcomes over the longer term. Benefits were measured in quality-adjusted life years (QALYs), and costs (2013-14) to the UK NHS included drugs, administration, monitoring, and hospitalisation. Costs and benefits were discounted 3.5 % per annum. Cost effectiveness of sequential biologic therapy was measured using an incremental cost-effectiveness ratio (ICER) compared to best supportive care (BSC). Extensive sensitivity analyses were performed to assess the impact of alternative assumptions on the results. RESULTS: Results indicate that over 10 years, switching to a second biologic following intolerance to or failure of a first is likely to generate more QALYs than BSC, but at a higher cost. Base case results suggest the ICER of the second biologic compared to BSC is £17,681 per QALY; however, sensitivity analyses indicate that changes in the efficacy of BSC, drug costs, dropout rates, and rates of hospitalisation have a significant impact, causing the ICER to range from less than £10,000 to over £50,000 per QALY. CONCLUSIONS: Further biologic therapy for patients with psoriasis who have previously been treated with biologic therapy may be cost effective, although there is considerable uncertainty in the results. Future studies should be designed to evaluate the clinical efficacy of biologic therapies in this subgroup with particular attention given to short-term and longer-term responses.

Psoriasis: guidance on assessment and referral.

This concise guideline summarises the key recommendations from the recent National Institute for Health and Care Excellence (NICE) clinical guideline on the assessment and management of psoriasis (CG153) that are relevant to the non-dermatologist. The aim is to highlight important considerations for assessment and referral of people with psoriasis, including identification of relevant comorbid conditions. Psoriasis is a common inflammatory skin condition and, especially when severe, can be associated with increased risk of cardiovascular disease, diabetes and depression. Functional, psychological and social morbidity can also be encountered, and the extent of the disability is frequently underestimated. Importantly, highly effective treatments are available. Appropriate assessment and referral of people with psoriasis therefore has the potential to improve outcomes by correctly identifying the appropriate treatment pathway. Assessment should involve not only disease severity but also the impact on patient well-being and whether the patient has any comorbid conditions, such as psoriatic arthritis, which requires rapid referral to a rheumatologist.

Incidence of cardiovascular disease in individuals with psoriasis: a systematic review and meta-analysis.

The relationship between psoriasis and increased risk of cardiovascular disease (CVD) is controversial. We critically evaluate 14 cohorts and meta-analyze the magnitude of CVD risk for the primary outcomes of CVD mortality, stroke, and myocardial infarction (MI), and establish subgroup risk for different psoriasis severities and age groups. Increased CVD risk was identified only in individuals with severe psoriasis (defined as requiring systemic therapy or hospital admission): the risk ratio relative to the general population was 1.37 (95% confidence interval (CI) 1.17-1.60) for CVD mortality, 3.04 (95% CI 0.65-14.35) for MI, and 1.59 (95% CI 1.34-1.89) for stroke. The relative risks of CVD were highest in the younger, severe psoriasis population (e.g., 3.10 (95% CI 1.98-4.86) for MI at 30 years), and absolute risks were greatest in older individuals with severe psoriasis (e.g., 23.2 excess MIs per 10,000 person-years at 60 years). Uncertainty remains about whether CVD risk is directly attributable to psoriasis, as the majority of studies failed to adequately adjust for key traditional risk factors.