First-line systemic treatment of psoriasis

The systemic treatment landscape of psoriasis has changed significantly in the last two decades. Introduced in 2003, biologic cytokine antagonists have become important therapies for psoriasis that are highly efficacious, fast-acting and relatively safe. Prior to the introduction of the biologics, the systemic treatment options for psoriasis were limited to methotrexate, ciclosporin, retinoids and fumaric acid esters (FAEs). These so-called conventional drugs typically have a slow onset of efficacy and may be associated with cumulative toxicity. Current psoriasis treatment guidelines recommend the use of conventional systemic agents as first-line treatment, whereas biologics are to be applied in case of treatment failure, intolerance or contraindication to a conventional therapy. This restricted second-line use of biologics is based partly on economic grounds – the costs of biologics are significantly higher compared with conventional treatments – and on a lack of data regarding the long-term safety of biologic treatments. Yet with the advent of biosimilars the biologic costs may decrease considerably, while to date no major safety issues have been observed with continuous biologic treatment. In line with this, several biologics have been granted marked authorization for first-line use in psoriasis. As a result, biologics may be prescribed to patients with psoriasis without a need for prior use of conventional therapies, but supporting evidence has been lacking.
In this issue of the BJD, Sticherling and colleagues describe results from the PRIME study, a German multicentre, randomized, open-label trial that compared head-to-head the efficacy of secukinumab, an anti-interleukin-17 biologic, with that of FAEs, a conventional agent approved for first-line use in Germany. In this study, 202 patients with chronic plaque psoriasis who had been na€ıve to systemic treatment were randomized to receive subcutaneous secukinumab or oral FAEs (Fumaderm, comprised mainly of dimethylfumarate) per label for 24 weeks. The primary outcome – the proportion of patients achieving at least 75% reduction in their baseline psoriasis area and severity index (PASI-75 response) at week 24 – was evaluated by blinded assessors. There was a significantly higher PASI-75 response for secukinumab than for FAEs, 90% vs. 34%, respectively. Other secondary efficacy outcomes were also in favour of secukinumab. Of note, only 43 (44%) subjects on FAEs had completed the 24-week follow-up period compared with 99 (94%) on secukinumab. Most FAE treatment withdrawals were related to gastrointestinal complaints and lymphocytopenia.
The study findings of the PRIME trial confirm important differences in short-term efficacy and speed of onset of action between secukinumab and FAEs. However, long-term assessment of efficacy, safety, cost-effectiveness and patient treatment satisfaction is still needed for optimal clinical decisionmaking. For example, biologics have been linked to a gradual decrease of efficacy, whereas FAEs have shown a favourable drug survival. In the current perspective, conventional systemic treatments will likely retain their status as preferred first-line therapy. Nonetheless, the clinical superiority in short-term treatment of highly effective biologics such as secukinumab may support their use as first-line therapy in specific cases requiring rapid disease control.
The PRIME trial is hopefully the first of studies that will generate high-quality evidence to better define the position of biologic therapies relative to that of the conventional systemic agents in the psoriasis treatment algorithms.