We developed an online survey to distribute to a maximum of 75 Spanish dermatologists with recognized experience in managing moderate to severe psoriasis. We targeted practitioners working in hospitals located throughout Spain.

Two Spanish coordinators collaborated to produce a 12-item questionnaire (Table 1) specifically for this study. The items, which all had closed or numerical answers, covered 4 basic areas: a)current management of moderate to severe psoriasis in clinical practice; b)transitioning from traditional systemic drugs to biologics; c)aspects of management of patients on biologic treatments, and d)assessments of first-line biologic agents according to different profiles of patients with moderate to severe plaque psoriasis. Responses to items 4, 9, 10, and 11 were given on a Likert-type scale from1 (least important) to5 (most important). Item 12, in which respondents ranked biologic agents as candidates for use in various types of patients, was also answered on a Likert-type scale—from 1(worst choice) to5 (best choice). The survey was sent to the dermatologists in October 2015 and data were collected for analysis in May and June 2016. The findings were used to draft a report of expert opinion across Spain.

The following statistics were compiled for quantitative variables: number of available responses, number of unavailable responses, mean (SD) evaluations and 95%CI of the mean, median (interquartile range), and highest and lowest evaluations (range of responses on the scale). Qualitative variables were described as frequencies and percentages.

Three of the 75 invited dermatologists did not respond (response rate, 96.0%). The respondents were distributed across Spain as follows: southern Spain (n=16); central Spain and the Canary Islands (n=17); northern Spain (n=12); Catalonia (n=15); and eastern coastal Spain (the Levant region) and the Balearic Islands (n=12). Thirty-three of the 72 respondents were men (45.8%) and 39 were women (54.2%).

All were specialists who worked in hospitals in Spain's national public health system.

Answers to the first survey question, about the percentage of patients with moderate to severe psoriasis being managed with a single therapy, showed that biologics were the most widely accepted choice, ranking ahead of traditional systemic drugs (Fig. 1). Ustekinumab was the biologic agent most prescribed by the largest group of respondents; the next most often prescribed were adalimumab and etanercept (Fig. 2).

Figure 1.

Percentage of patients managed with each approach alone (x axis) by the different percentages of dermatologists (y axis) expert in the treatment of moderate to severe psoriasis.

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Figure 2.

Percentages of patients currently treated with each biologic (x axis) by the different percentages of dermatologists (y axis).

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When the respondents considered transitioning a patient from a traditional systemic to a biologic therapy, 35.7% thought that at least 2or 3conventional systemic alternatives or phototherapy should have failed, whereas 64.3% did not share that opinion. The main reason for transitioning to a biologic was unstable disease activity. The second most important reason was that high doses of a conventional systemic therapy were required to control symptoms (Fig. 3).

Figure 3.

Factors that lead the dermatologists to transition a patient from a traditional systemic treatment to a biologic and to limit the amount of time a patient stays on a traditional systemic therapy. The reasons were ranked on a scale of 1 (least important) to 5 (most important).

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Patients stayed on conventional systemic treatments for 1to 2years before transitioning to a biologic according to 64.3% of the dermatologists and for 6months to a year according to 21.4%. Only 14.3% reported that patients were kept on traditional systemic therapies for more than 2years.

Our data show that dermatologists are now keeping patients on conventional systemic treatments for less time than was reported in 2013 based on an online survey of members of the Psoriasis Working Group (PsWG) of the Spanish Academy of Dermatology and Venereology (AEDV).14 Prescribers are also currently more likely to transition patients with unstable disease from traditional systemic therapy to biologics in order to optimize treatment. The 2013 report found that 73% of respondents waited 2or more years to switch patients away from a traditional systemic treatment to a biologic, even though a considerable percentage (66%) thought the wait should be shorter. Our survey results suggest that Spanish practice is changing, as only 14.3% of patients now stay on conventional treatment for 2years. The consensus statement of the PsWG published in 2016 even reported the opinion that biologics should be considered first-line options for treating moderate to severe psoriasis, alongside conventional systemics.9

Change is also evident in the criteria dermatologists use to shorten the transition period. Toxic effects of systemic treatment once reigned as the main criterion, whereas loss of response or possible unevenness of response are now main concerns. The experts continue to take scant account of concomitant conditions when making this decision.

Most respondents order tests every 3to 6months, as advised by the UK's National Institute for Health and Care Excellence (NICE).15 There is considerable variation in tuberculosis screening practices. Screening only at the start of biologic treatment is the approach that predominates,16 even though the Spanish PsWG's 2016 consensus statement9 recommends repeated screening while the patient is on such therapy. However, consensus for that statement was reached in 2012 and 2013, several years before the 2016 publication date. The results of the present survey, therefore, reflect the more up-to-date clinical practice opinions of dermatologists.

The dermatologists surveyed considered the following criteria to be important when deciding to recommend biologic therapy: PASI score≥10 or an affected body surface area of at least 5% to 10%; patient perception of having severe disease (Dermatology Life Quality Index>10); and the presence of psoriatic arthritis, consistent with an earlier PsWG consensus statement.6

The introduction of biologic drugs in clinical practice has improved the efficacy of psoriasis treatment, as shown by the opinion of 78.6% of our respondents that treatment should achieve at least a 90% improvement in the PASI score—the equivalent of an absence of clinical signs (clearing) or minimal signs of disease—or even that a PASI score of 3 or less should be sought. These goals are much more ambitious than the therapeutic objectives suggested by previously published guidelines, which recommend seeking 75% of more improvement in the score. The response criterion of 90% improvement also offers a more discriminating objective in terms of bettering patients’ quality of life17 than the lower goal of a 75% change in PASI score.

In clinical scenarios in which there is still no firm evidence to guide the treatment of moderate to severe psoriasis, therapy must be tailored to the patient's situation.5 The prescriber must therefore apply criteria based on experience gained by experts during routine clinical practice. Our survey, which provides data on the main criteria used by Spanish dermatologists when choosing a biologic, sheds light on practice in such scenarios.

Most respondents chose etanercept for pediatric patients (78.6%); adalimumab or etanercept for patients who also have psoriatic arthritis (64.3%); and ustekinumab for patients who have to travel away from home often (78.6%), whose adherence is poor (71.4%), or who have a history of multiple sclerosis or demyelinating disease (64.3%). The first-choice biologics for other scenarios varied greatly.

Some of these findings are consistent with opinions reported previously14 or with some guidelines.11 Our informants, all experts in psoriasis, expressed the novel opinions that secukinumab would be one of the biologics of choice for patients who are obese or have metabolic syndrome and that apremilast would be a good choice for patients with a history of neoplastic disease, chronic infection, or latent tuberculosis.

Warnings and contraindications are important to consider when choosing a biologic. The panel named ustekinumab, of which a maintenance dose is taken every 12weeks, as appropriate for scenarios in which there are adherence problems. It was also considered a candidate for scenarios in which anti-tumor necrosis factor (TNF) therapy is contraindicated (lupus erythematous and other autoimmune diseases, advanced heart failure, and demyelinating diseases), a suggestion that has been noted in the literature.18

Etanercept was chosen as the first-line biologic for pediatric populations. The respondents’ choice could be explained by the fact that etanercept was the first biologic approved by the European Medicines Agency (EMA) for the treatment of chronic severe plaque psoriasis in children aged 6years or older.19 Alternative explanations are that etanercept is the biologic agent that has been most widely studied in randomized clinical trials in children and adolescents20 to date, and it is the only one for which long-term extension studies have been carried out.21

Other biologics have begun to be subjected to such study. Examples are adalimumab, recently approved by the EMA for pediatric use and the subject of a trial in children and adolescents22 and ustekinumab.23 The range of treatments available for pediatric use is increasing.

Previously published guidelines for treating patients aged 65years or older recommend prioritizing safety, suggesting intermittent treatment approaches and lower doses than those listed in product summaries.24 The group of experts we surveyed chose etanercept as their first choice, presumably because of its short half-life, good safety and efficacy profiles,25 and tolerance in patients of advanced age.26 Recently published Italian guidelines point out that any of the biologics could possibly be used in this population if patients are monitored adequately, since few studies of adalimumab, etanercept, and ustekinumab in the elderly have as yet appeared.27,28

The risk of reactivation of latent infection or of opportunistic or serious infection is lower in patients with psoriasis than in those with other inflammatory diseases because psoriasis patients have different characteristics and are not usually on additional immunosuppressant therapies. However, risk is slightly higher in patients on infliximab or adalimumab than in those on etanercept or ustekinumab.29 The recommendations published by the AEDV's PsWG9 and the Italian group11 suggest that the risk of reactivation is lower with etanercept, based on wider experience using that biologic in patients with chronic hepatitis C and HIV infections.30,31 However, for this scenario our surveyed experts selected apremilast, an oral biologic agent that has lower efficacy but that seemed to have less of an immunosuppressant effect in a recent trial.32

The association of arthritis and psoriasis affects the choice of biologic, and guidelines recommend the use of an anti-TNF agent as the first line of therapy. These drugs have demonstrated efficacy in the 5key domains of this scenario: 1) peripheral arthritis; 2) skin and nail lesions; and the involvement of 3) axillas, 4) joints of fingers or toes (dactylitis), and 5) entheses (evidence level 1+).33 Anti-TNF agents have also been shown to inhibit the radiologic progression of psoriatic arthritis.34,35 Our respondents’ opinion that etanercept and adalimumab were the best choices could be due to reports of superior cost-effectiveness.36 However, it is important to also bear in mind that when we collected data for this analysis (in May–June 2016) the experts had not yet accumulated much experience with new biologics, especially secukinumab, in psoriatic arthritis. That drug is a well placed candidate at present, given the observation of good results at even lower doses than those generally used in psoriasis (see the FUTURE137 and FUTURE238 studies).

Anti-TNF agents are contraindicated in patients with congestive heart failure (gradesIII–IV). In patients with this concomitant condition ustekinumab could be considered the treatment of choice.

The Spanish dermatologists who responded to our survey preferred etanercept for intermittent treatment regimens, consistent with another survey14 and European guidelines.11 Their choice could be due to the pharmacokinetic characteristics of this drug, which has a shorter half-life and has proven effective in intermittent protocols and retreatments without causing additional adverse events.39,40

Recently published Spanish guidelines point to the difficulty of managing psoriasis in certain locations—such as the scalp, nails, palms, and plantar surfaces—and the scarcity of well organized information and high levels of evidence about such treatment difficulties.41 Guidelines on the use of biologics in patients with psoriasis in difficult-to-treat locations published in 2015 named infliximab and etanercept as good choices in scalp psoriasis (grade A recommendation, evidence level 1). The strength of recommendation is lower for adalimumab (grade B, level-1 evidence) and lower still for ustekinumab (grade C, level-1 evidence).8 The ESTEEM1 and 2trials recently demonstrated the efficacy of apremilast in these types of psoriasis,42 and the GESTURE trial concluded that secukinumab was very effective in the treatment of palmar-plantar psoriasis.43

Obesity plays a role in response to all biologic therapies, although differences often fail to reach statistical significance. The possibility of adjusting the dosage of infliximab according to weight offers the opportunity to achieve similar results in obese and nonobese patients.44

Tailored management is important in women who are pregnant or planning pregnancy, when the drug's half-life and the severity of disease must be weighed in the balance. Biologics used to treat psoriasis are categoryB drugs. In fact, a biologic's average half-life must be factored in whenever a woman of childbearing age is treated. Etanercept has the shortest half-life (3days), infliximab the next shortest (10days), followed by adalimumab (15days) and ustekinumab (3weeks). Contraceptives are recommended during treatment and up to 3weeks after suspending treatment with etanercept, 15weeks after stopping ustekinumab, 5months after stopping adalimumab, and 6months after stopping infliximab.24 Because immunoglobulinG is transported to the fetus during the second and third trimesters, guidelines recommend interrupting treatment with infliximab and adalimumab during the last trimester to prevent neonatal immunosuppression.11 In a case series describing 5pregnant women treated with ustekinumab, 1pregnancy resulted in miscarriage.45

A high prevalence of metabolic syndrome (14% to 40%) has been reported in psoriasis.46 An underlying inflammatory state is common to both conditions,47 as evidenced by altered levels of secretory proteins such as adponectin and leptin, which regulate the release of such mediators as TNF; interleukins6, 7, and 22; and interferon-γ. Drugs like acitretin, ciclosporin, and methotrexate can aggravate some components of metabolic syndrome, so biologics, which target more specific components of disease, are considered the first line of therapy for patients with this condition.48 Our survey found that the dermatologists’ choices for patients with moderate to severe psoriasis and metabolic syndrome were adalimumab, ustekinumab, and secukinumab.

Because ours was an opinion survey of 73 specialists in different hospitals and geographic areas, the highly variable results must be interpreted with caution. Nonetheless, the findings provide important information that reflects the professional experience and routine clinical practice of dermatologists.