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Role of biologics: anti-TNFs


determining immunogenicity can be helpful in deciding in which patient switching could be beneficial and can be part of a personalised treatment regimen.2


Etanercept


The use of ETN was approved by the European Medicines Agency (EMA) in 2004 for psoriasis and in 2002 for psoriatic arthritis. ETN was approved by the Food and Drug Administration (FDA) in 2004 for the treatment of moderate-to- severe psoriasis. The degree of immunogenicity of ETN has been demonstrated to be low (<2%), probably because of its human origin and protein structure.3


ETN is administered subcutaneously at the dose of 50mg once per week (or twice weekly during the initial 12 weeks of treatment). The half-life of ETN is 68±18hours. The therapeutic programme approved for the treatment of psoriasis is 50mg twice a week for 12 weeks followed by 50mg every week in a continuous administration.


ETN is the only biologic agent that has been approved for the treatment of psoriasis in children, from the age of six years, and it has demonstrated low rates of side effects in the paediatric population.4 The efficacy of ETN has been demonstrated in randomised clinical trials. Improvement equal to or greater than 75% with respect to baseline Psoriasis Area and Severity Index (PASI 75 response) is reached in 34% and 44% of the patients treated with ETN 50mg per week and in 49% and 59% using the dose of 50mg twice a week, at week 12 and 24 of treatment, respectively.5


ETN has shown good results in the treatment of nail psoriasis.6


Also, there are 12


several case reports describing the efficacy of ETN for the treatment of erythrodermic and generalised pustular psoriasis.7,8 ETN has also been demonstrated to be useful in combination with other systemic treatments or phototherapy in patients that show lack or loss of efficacy. The combination of ETN with phototherapy has been reported to achieve good results in a study that included 86 patients and in which the treatment with ETN 50mg twice a week in combination with nbUVB, achieving a PASI 75, 90 and 100 in 84.9%, 58.1% and 26% at week 12, respectively.9 The combination of ETN with MTX has been demonstrated to be more effective than each agent used separately and is to be considered a good alternative


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in cases that require combined treatment.10


In a controlled randomised


study, it was concluded that the combination of ETN 25mg per week with acitretin 0.4mg/kg/day shows the same efficacy as ETN 25mg twice per week; thus, the combination of ETN with acitretin is a good option to manage patients with psoriasis without increasing treatment associated toxicity.11


The side effects more


commonly associated with the administration of ETN are the following: injection site reaction, allergic reactions, headache and upper airway infections. Infections represent around 21% of the side effects associated with the use of ETN, including sinusitis and upper airway infections. The rate of severe infections is detected in 0.4% of patients treated with ETN.3


Patients receiving anti-TNF agents cannot be immunised using live agents.


Adalimumab


Adalimumab was approved by the EMA in 2005 for psoriatic arthritis and in 2007 for psoriasis, and by the FDA in 2004 for the treatment of psoriatic arthritis and in 2008 for the treatment of psoriasis. The half-life is two weeks and it has to be administered subcutaneously. The initial dosage to be administered is 80mg in a unique dose, 40mg after seven days and every two weeks subsequently. The efficacy of ADA has been


demonstrated in clinical trials, achieving a PASI 75 response in 53–80% of patients treated.13


The presence of anti-ADA


antibodies has been detected in 8.4% of patients in clinical trials, and up to 40% in real life series, and is frequently associated with a reduction in the efficacy of this agent. The combination of ADA with methotrexate has the ability to reduce the immunogenicity and clearance of ADA, leading to better responses when compared to ADA in monotherapy.14 Regarding safety, injection site reactions are the most commonly described adverse event (in 20% of the patients), even though these are slight reactions and the treatment does not usually require to be discontinued. The rate of infections in patients treated with ADA is one patient per year, which can be compared to 0.9% per year in patients treated with placebo.15


There have been several cases of ADA-induced lupus-like and autoimmune phenomena, which, together with worsening of demyelinating disease, are considered class effects of anti-TNF agents. Congestive heart failure (NYHA


class III-IV) is a contraindication for treatment with ADA or IFN, and requires careful consideration in candidates to ETN treatment.16


Infliximab


Infliximab (IFX) was approved for use by the EMA in 2004 for psoriatic arthritis and in 2005 for psoriasis. IFX was approved by the FDA in 2006 for the treatment of moderate-to-severe psoriasis. IFX is a chimeric monoclonal antibody with a half-life of 8–9.5 days. It is administered at a dose of 5mg/kg by intravenous infusion during two hours. It is recommended to be administered in an emergency room or day hospital facility with the capacity to treat infusion reactions to this agent, which can be severe. Treatment with IFX includes an induction phase, when the drug is administered at weeks 0, 2 and 6, and then every eight weeks.


IFX is one of the biologic agents to be used in severe cases, when a rapid time-to-onset of action is required because the initial results may be seen at 2 weeks after the first administration.17,18 Three main placebo-controlled randomised clinical trials have demonstrated the efficacy of IFX in moderate-to-severe psoriasis.17–19


At


week 10, 80% of the patients reach PASI 75 and the response may persist in a significant proportion of patients: 54–61% of patients sustain a PASI 75 response, and 34–45% of patients sustain a PASI 90 response at week 50. One of the causes that may explain the loss of efficacy is the development of anti-IFX antibodies, which can be detected in at least 19% of patients.17,20,21 The efficacy of IFX in nail psoriasis has been evaluated in the phase II EXPRESS study, in which 378 patients were included. In 305 of these patients, nail psoriasis was detected, and the response to IFX was evaluated at week 50 using the NAPSI score. In 59.7% of patients, the NAPSI was significatively reduced at week 50 compared to the basal NAPSI, and in 44.5% there was a complete clearance of nail disease at week 50.22


IFX can be considered the biologic agent of choice in severe cases of erythrodermic psoriasis or generalised pustular psoriasis because of its capacity to provide rapid clearance in these patients.23,24 The combination of IFX with classical systemic treatments is recommended in patients in whom loss of response is suspected. Baranauskaite et al have


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