Biologics

Biologics represent a new generation of drugs which have been developed to treat chronic immune-mediated inflammatory conditions such as psoriasis (but also rheumatoid arthritis and chronic inflammatory bowel conditions such as Crohn’s disease). In common with other systemic drugs, they are reserved for those who have severe disease, and in addition, it is usual for patients to have unsuccessfully tried the other systemic options before being offered biologic drugs. This section briefly considers the three biologic drugs that are currently available for the treatment of plaque psoriasis in the UK. However, new biologic drugs are being developed and this list in unlikely to be exhaustive for very long. For example the National Institute for Health and Clinical Excellence is due to publish its technology appraisal on Ustekinumab (which is a human monoclonal antibody) in September 2009.

The basic principle of biologic drugs is that they interfere with a very specific part of the inflammatory process thus preventing the development of psoriatic lesions. Because the drugs are so targeted it is hoped that the longterm side effects will be less than other systemic medications, but there is no long-term data that categorically confirms this judgement. Some considerable attention is being given, by the British Association of Dermatologists, to collecting data about the effects of biologic drugs thus creating what is called a biologics register (British Association of Dermatologists, 2007).
In April 2009, there were three biologic drugs available for the treatment of severe plaque psoriasis. Table 8.7 outlines what the three drugs are, the dosage and recommendations from NICE as to how and when they should be prescribed. A fourth drug (Efalizumab, Raptiva™) was available until February 2009 when three patients experienced severe adverse effects. As a consequence of this, the European Medicines Agency issued recommendation that the product should not be marketed, that no further prescriptions should be issued and that those already on the drug should talk to their doctor about finding an alternative (European Medicines Agency, 2009).

Table 8.7 Biologic drugs and prescribing regimes.   Name   Mode of action   Recommended prescribing regime   Delivery   Etanercept (EnbrelTM)   Known as a genetically engineered recombinant protein, it binds to TNF-α molecules preventing them from activating skin cells thus preventing inflammation (Jackson et al., 2007).   Twice weekly doses of 25 mg for up to 24 weeks or until remission occurs, should further treatment be needed the same dose should be followed (i.e. it is an intermittent treatment). Suitable for individuals with PASI 1 of 10 or more and a DLQI 2 of 10 or more Should be discontinued after 12 weeks if the response is inadequate, i.e. there is a less than 75% reduction in PASI or less than 50% reduction in PASI accompanied by a 5 point reduction in DLQI (National Institute for Health and Clinical Excellence, 2006)   Subcutaneous injections   Infliximab (RemicadeTM)   Known as a monoclonal antibody it binds to all three forms of TNF-α thus affecting the inflammatory process   An initial 5 mg/kg infusion over 2 hours, followed by further 5 mg/kg infusions at 2 and 6 weeks. Subsequent infusions are then given at 8-week intervals Suitable for individuals with PASI of 20 or more and a DLQI of 18 or more Should be discontinued after 10 weeks if the response is inadequate, i.e. there is a less than 75% reduction in PASI or less than 50% reduction in PASI accompanied by a 5 point reduction in DLQI (National Institute for Health and Clinical Excellence, 2008a)   Infusion   Adalimumab (HumiraTM)   Known as a monoclonal antibody which binds with TNF-α blocking interaction with cell-surface receptors and limiting the promotion of inflammatory pathways   An initial dose of 80 mg followed by 40 mg injections every other week starting 1 week after the initial dose. Suitable for individuals with PASI of 20 or more and a DLQI of 18 or more Should be discontinued after 16 weeks if the response is inadequate, i.e. there is a less than 75% reduction in PASI or less than 50% reduction in PASI accompanied by a 5 point reduction in DLQI (National Institute for Health and Clinical Excellence, 2008b)   Subcutaneous injection     1 PASI is the Psoriasis Area Severity Index which is a validated method for assessing disease severity. Further details about how to carry out a PASI. 2 DLQI is the Dermatology Life Quality Index which is a validated questionnaire that assesses the impact that skin disease has on quality of life. It is discussed in further detail in Psychological and social aspects of skin care.

Each biologic drug will have its own contraindications which can be found in the British National Formulary (British Medical Association and Royal Pharmaceutical Society of Great Britain, 2008), Electronic Medicines Compendium (Datapharm, 2009) and summarised in the British Association of Dermatologists Guidelines (Smith et al., 2005). However, a concern which is relevant to all biologic drugs is that of infection including risk of tuberculosis. All psoriasis patients being considered for biologic therapies must have a chest X-ray and a Mantoux test, both of which must be negative prior to commencing therapy. If for any reason, there is doubt about the result or an individual can’t have a Mantoux test as they are on immunosuppressive therapy they should be referred to a thoracic physician (Smith et al., 2005).