Sequential use of biologics in the treatment of moderate-to-severe plaque psoriasis (original) (raw)

2012, British Journal of Dermatology

A number of biologic agents, including the tumour necrosis factor (TNF) antagonists etanercept, adalimumab and infliximab, and the interleukin (IL)-12/IL-23 antagonist ustekinumab, are available for the treatment of moderate-to-severe plaque psoriasis in the U.K. Currently, the selection of the first biologic, and the choice of sequential biologics in the event of efficacy/tolerability concerns, is made using a limited evidence base. The efficacy of biologics, the potential mechanisms of primary and secondary failure and the evidence for sequencing therapy among TNF antagonists and between TNF antagonists and IL-12/IL-23 blockade are reviewed. As psoriasis biologics registers begin to produce longterm safety and efficacy data, therapy decisions in plaque psoriasis may become more objective, and it may be possible to individualize treatment based on clinical or pharmacogenetic information. The management of moderate-to-severe plaque psoriasis has been significantly enhanced by the addition of biologic therapies to the therapeutic armamentarium. Four such drugs are approved in the U.K.: three TNF antagonists (etanercept, adalimumab, infliximab) and the IL-12/IL-23 antagonist, ustekinumab. These drugs have different mechanisms of action and all have proven efficacy in plaque psoriasis. 1 The choice of first biologic is directed by physician and patient preference, disease phenotype (e.g. the need for rapid control in severe inflammatory disease), the presence of comorbidities such as psoriatic arthritis (PsA), the presence of contraindications to TNF antagonists (such as demyelinating disease), treatment goals, local and national guidelines, and local funding and access agreements. Unfortunately, a significant number of patients will discontinue their first biologic because of primary failure (lack of initial efficacy), secondary failure (loss of efficacy with time) or because of intolerance/side-effects. Studies in Crohn's disease and rheumatoid arthritis (RA) have demonstrated benefit in transitioning from one biologic to another, although the efficacy of a second agent may not reach the benefit of the first. 2-4 In this article, we discuss the efficacy of biologics in moderate-to-severe plaque psoriasis, potential mechanisms of primary and secondary failure, and review the evidence for sequencing therapy between TNF antagonists and from TNF antagonists to IL-12/IL-23 blockade. Methods Papers were identified from MEDLINE and EMBASE using the following search terms: psoriasis AND (ustekinumab OR etanercept OR infliximab OR adalimumab OR efalizumab OR biologic*) AND (switch* OR sequence*). Thirty-two papers were retrieved, and those reporting efficacy and/or safety data for biologics in the treatment of plaque psoriasis were considered for inclusion. Particular focus was given to papers reporting switching between biologics. Not all the doses and/or regimens for each agent that are discussed in the article are approved for use; local prescribing information should therefore be referred to for the approved use of each agent. Other