Biologics for psoriasis: current evidence and future use

Psoriasis is a chronic immune-mediated inflammatory disease which, in its severe form, is associated with significant comorbidities and increased mortality.1, 2 Effective, long-term treatment of plaque psoriasis is challenging. Dermatologists are faced with an array of treatment options, and there is a wide variability in both initial response to treatment, response over time and side-effects. Consequently, dermatologists must continually adapt and/or change therapies as required, on a patient-by-patient basis. Several biologic agents have emerged over the past 10 years for the treatment of moderate-to-severe plaque psoriasis, providing valuable alternatives for patients who have failed to respond to conventional topical and systemic agents or for whom these agents are contraindicated. These biologics are diverse in nature, but share an ability to block specific steps in the inflammatory process, thereby offering a targeted approach to therapy, while providing valuable insights into the mechanisms underlying disease pathology.3 Although tumour necrosis factor (TNF)-α signalling is the target for several of the biologics in use for psoriasis, including infliximab, adalimumab and etanercept, other important targets have emerged. These newer targets include interleukin (IL)-12/IL-23, which are targeted by ustekinumab, and IL-17. Biologic agents have entered mainstream clinical practice for the treatment of moderate-to-severe plaque psoriasis, and clinical experience with them is expanding rapidly. An in-depth understanding of the real-life capabilities, in terms of both efficacy and safety of biologics is emerging, in large part through data from national registries. However, biologic agents represent a relatively recent therapeutic option for psoriasis and, thus, there is a relative paucity of long-term safety data. Treatment guidelines rank biologics as the third-line treatment option for plaque psoriasis, after topical, photo and systemic therapies.4, 5 The efficacy of biologics in plaque psoriasis is now generally accepted, with a number of studies reporting positive data for up to 3 years of continuous use,6-9 whereas demonstration of safety requires ongoing evaluation and long-term follow-up. In the U.K., the British Association of Dermatologists (BAD) Biologic Interventions Register (BADBIR) collects data on the long-term safety of biologic and conventional systemic treatments for psoriasis.10 Inclusion in the BADBIR is recommended by the National Institute for Health and Clinical Excellence (NICE) for all patients with psoriasis receiving biologic therapy. For patients with moderate-to-severe psoriasis who have not responded to conventional systemic therapy such as methotrexate, several factors may influence the choice of first biologic, including physician and patient preference, disease severity and comorbidities. The BAD and European treatment guidelines4, 5 recommend TNF antagonists as first-line biologic therapy due to the availability of clinical safety data across a number of disease areas. However, these guidelines may be adjusted as psoriasis biologics registers and open-label extension studies begin to provide long-term safety profiles. Clinical trial data inform us that patients whose psoriasis has improved significantly on a biologic should generally be continued on their treatment regimen in order to prevent relapse. This guidance is particularly pertinent with the current absence of systemic biomarkers of disease remission. However, dermatologists may choose to stop a specific biologic therapy in the event of slow or inadequate response, occurrence of adverse events or under special circumstances, such as elective surgery, vaccination with live virus or pregnancy.4, 5 In such cases where a biologic treatment fails to show initial or prolonged efficacy, it is already clear that sequential use of these agents is both an effective and valuable treatment strategy. Importantly, different biologics appear to behave as distinct drug classes in this regard, with failure of one agent not necessarily predictive of failure with another.11 Crucially, however, there is little formal guidance on how best to sequence the use of biologic agents, and most of the evidence available to inform such decisions is anecdotal. It is clear that the treatment of moderate-to-severe psoriasis is a complex area, with the guidelines for best practice still evolving. For biologic therapies, a number of key questions remain: How do the safety and efficacy profiles of these agents compare with each other and with non-biologic treatments? At what stage and in what order should they be introduced? Can individual biologic therapies be used intermittently without losing efficacy? How should their sequential use be managed in patients demonstrating adverse events or inadequate disease control? Are there data available to guide treatment decisions and facilitate the prediction of short- and long-term response and toxicity? This supplement aims to address these questions by reviewing the current evidence base for biologics in the treatment of moderate-to-severe psoriasis, specifically focusing on long-term safety data, the available information from clinical practice on switching between therapies, and real-world experience from experts on the use of biologics. The articles aim to provide practical insights to help dermatologists address the challenges they face in deciding on appropriate treatment for individual patients. Editorial support for this article was funded by Janssen. Editorial control resided with the author. The author received no honoraria or other form of financial support related to the development of this manuscript. Funding for publication of this supplement was provided by Janssen. C.E.M.G. has received honoraria and/or research support from Abbott, Biotest, Celgene, Incyte, Janssen, LEO, MSD, Novartis, Pfizer and Stiefel U.K., a GSK company.