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Management


biologics are more effective than etanercept and all conventional treatments. Head-to-head trials indicate the superiority of adalimumab and infliximab over methotrexate (MTX), the superiority of ustekinumab over etanercept, the non-significant superiority of ciclosporin over MTX, and the dose-dependent efficacy of etanercept and ustekinumab. Fumaric acid is as efficacious as MTX. Safety of treatments could not be pooled owing to a lack of standardisation in reporting across trials. Another meta-analysis (including data from trials with ustekinumab, infliximab, adalimumab and etanercept) in which the SPC-approved conditions of use and clinically relevant time points were taken into account20


has shown that at the end for secukinumab.8


Data on efficacy and safety included in the Summaries of Product Characteristics (SPCs) are based on the results observed in patients enrolled in randomised clinical trials, a subpopulation of individuals that is not representative of the overall population to be treated; up to 30% of patients in a registry in Spain would have been ineligible to participate in randomised clinical trials in psoriasis, and they have an increased risk (incidence rate ratio, 2.7) of serious adverse events.9


Disease-related factors


Disease-related factors might also affect the response to biologic treatments in psoriasis. They include severity10


and


duration of disease, age at diagnosis, and palmo-plantar or nail involvement, among others. In addition, 6–42% of psoriasis patients, particularly with a moderate-to-severe form of the disease, suffer from PsA,11


whose disease is refractory to non- biologic disease-modifying anti- rheumatic drugs (DMARDs), except for the management of axial disease, where non-biologic DMARDs have not been shown to provide a consistent benefit.14


Previous biologic treatment


Furthermore, the link between a previous biologic treatment and response to the current treatment should be considered. Patients who had received previous biologic therapies achieved lower PASI50 response rates with etanercept at week 24 than patients who were biologic-naïve.15 Biologic-naïve patients have been reported to have significantly higher PASI75 and PASI90 response rates at six months and one year following treatment with adalimumab,16 secukinumab.18


ustekinumab17 and and not all the available


therapeutic agents are equally effective on the skin and joint manifestations of psoriatic disease. On the other hand, a history of PsA may be associated with an increased probability of partial response to some biologic agents, although in a recent study,12


300mg secukinumab 20


proved more effective that etanercept at improving physical functioning of psoriasis patients with PsA, and was much superior to etanercept in improving the skin manifestations of psoriasis.13 Biologic agents approved for the treatment of PsA are usually introduced as a second-line treatment in patients


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According to this published meta-analysis, in placebo-controlled trials, infliximab was the most efficacious (risk difference (RD) 76%, 95% confidence interval (CI) 73–79%). Adalimumab (RD 61%, 95% CI 56–67%), and ustekinumab 45mg (RD 63%, 95% CI 59–66%) and 90mg (RD 67%, 95% CI 60–74%) each had similar efficacy. These


The efficacy of systemic treatments can be compared indirectly with meta- analyses of randomised clinical trials or directly when head-to-head trials are available. In a recently published meta-analysis (which included trials with infliximab, adalimumab, ustekinumab, etanercept), the efficacy was assessed as PASI75 response rates at the time of primary efficacy measurement (weeks 8–16).19


of the induction phase (week 24), ustekinumab 45mg has the greatest probability of achieving PASI75 response (RD 75.5%, 95%CI 71.5–79.4%), followed by ustekinumab 90mg, infliximab, adalimumab and etanercept. At the time points recommended for primary failure assessment according to the approved SPCs, ustekinumab 45mg (at week 28) also has the greatest probability of achieving PASI50 response (RD 80.7%, 95%CI 77.2–84.2%), followed by ustekinumab 90mg, infliximab, adalimumab and etanercept. Another recently published meta- analysis (including data from trials with infliximab, secukinumab, ustekinumab, adalimumab, etanercept and apremilast) has evaluated the efficacy of long-term (24–28 weeks) treatment of moderate to severe psoriasis.21


With respect to PASI75,


pooled risk ratios (RR) were: infliximab 13.07, 95% CI 8.60–19.87; secukinumab 11.97, 95% CI 8.83–16.23; ustekinumab 11.39, 95% CI 8.94–14.51; adalimumab 8.92, 95% CI 6.33–12.57; etanercept 8.39, 95% CI 6.74–10.45; and apremilast 5.83, 95% CI: 2.58–13.17. The corresponding results for PASI90 response were: secukinumab 40.15, 95% CI 20.97–76.89; ustekinumab 31.63, 95% CI 19.43–51.51; infliximab 31.00, 95% CI 13.45–71.46; adalimumab 23.17, 95% CI 12.51–42.91; etanercept 19.14, 95% CI 11.59–31.60; and apremilast 13.00, 95% CI 1.74–97.25. With respect to the addressed safety parameters, no differences were seen between adalimumab, etanercept, secukinumab or infliximab versus placebo.


Head-to-head studies have shown superior efficacy of secukinumab versus etanercept22


and ustekinumab,23 of


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