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Long-term safety – part 1/2

Long-term safety of biologics in moderate-to-severe plaque psoriasis

This two-part chapter will provide expert perspectives from two leading dermatologists, Professor Robert Gniadecki (University of Copenhagen) and Professor Luigi Naldi (Centro Studi GISED), on the long-term safety issues associated with cumulative immunosuppression

Long-term safety of biologics: Part 1 – Assessment of safety in psoriasis and lessons from other disease areas

Robert Gniadecki MD Department of Dermatology, Bispebjerg Hospital and Faculty of Health Sciences, University of Copenhagen, Denmark

Professor Gniadecki begins by discussing the importance of assessing the long-term safety of biologics, and risks of unpredictable adverse events over time.


Psoriasis is a chronic disease requiring continuous treatment over years. It is therefore important to understand the long-term safety of the drugs used for the therapy of psoriasis and psoriatic arthritis. In this paper, we review the safety of the long-term treatment with anti-tumour necrosis factor (anti-TNF) agents (adalimumab, etanercept, infliximab) and anti-interleukins 12 and 23 (anti-IL-12/23) (ustekinumab). The sources of data were the randomised clinical trials, open-label extension studies, post-marketing surveillance databases and clinical registries. The safety profile of the biologics used in dermatology resembles that documented for other indications, with a trend towards a slightly lower incidence of severe adverse events (AEs) in psoriasis compared to patients with rheumatic diseases or inflammatory bowel disease.1 Evidence suggests that biologics seem to be

protective against cardiovascular AEs, but further data are required to verify this. The overall risk of unpredicted AEs during the long-term treatment seems to be well below 0.1%/year. It can be concluded that the biologics have a very high benefit/risk ratio and lack any cumulative toxicity, which makes them ideal for the long-term treatment of psoriasis and psoriatic arthritis.

Introduction: How biologics have transformed the clinical landscape The concept of how moderate and severe psoriasis should be managed on a long-term basis evolved over the past ten years. Conventional systemic drugs such as methotrexate, ciclosporin and retinoids pose a risk of cumulative organ toxicity

and have therefore been used in rotational regimes in which the patient remained on a single drug for only a limited period of time. Treatment holidays were advocated. Unavoidable psoriasis relapses were considered an acceptable trade-off for the sake of safety. This view changed considerably with the advent of biologics. First, an enormous investment in research on the clinical importance of psoriasis revealed that this disease has a profound negative effect on the quality of life of patients, to a magnitude comparable with other serious chronic diseases such as rheumatoid arthritis, congestive heart disease, chronic obstructive pulmonary disease or diabetes. It was realised that disease exacerbations, inevitable with the rotational regimens, might no longer be an acceptable option for the patients. Second, clinical trials with the biologics showed conclusively an excellent short-term efficacy of continuous drug administration. When the treatment is stopped and reintroduced, up to 20% of previous responders will lose efficacy.2 Thus, intermittent therapy with biologics leads us nowhere and the best strategy is to keep the patient on treatment for the longest possible time.

The concept of a very long (in principle life-long) immunosuppressive therapy raises important safety concerns. Is there a

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