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Sequential use of biologics


with the currently available data. However, infliximab has been shown to have the shortest TOA (3.5 weeks), followed by ustekinumab (high dose 4.6/low dose 5.1 weeks [not weight adapted]), adalimumab (4.6 weeks) and etanercept (high dose 6.6/ low dose 9.5 weeks). The time necessary for a treatment to become effective is crucial for patients and physicians but has been largely neglected in the reporting and comparison of clinical trials in dermatology.13


Based on this


systematic review, infliximab is preferred above the other biologics if a prompt onset of action is needed. Low-dose etanercept seems to be very slow in improving psoriasis. When considering TOA, it is important to note that infliximab is the only biologic approved for psoriasis that is administered intravenously, while all other approved biologics are given to patients as subcutaneous injections. This difference in mode of administration could play a role but requires further investigation. The haematological side effects, the increased risk of infections and the slight increase in some malignancies seem to be comparable among the biologics. On short-term side effects, the biologics differ slightly. Subcutaneous injections with adalimumab, etanercept and ustekinumab may cause a local (skin) reaction at the injection site. Infliximab may cause a generalised infusion reaction. Precautions with one dose of oral corticosteroids and antihistamines can be used to prevent this infusion reaction.


In cases where infliximab treatment has been interrupted for four months or more, restarting this therapy may cause even more severe infusion reactions and therefore should be avoided.


Prospective studies including registries will give insight into long-term safety and rare adverse events.14


The age of patients plays a role in selecting a biologic. Until now, only etanercept has been approved for childhood psoriasis.15,16


Some case reports with


infliximab in children are available. Prospective cohorts may provide data in the future for geriatric patients with psoriasis. Prospective randomised trials have not been performed for psoriasis in pregnant and lactating women and, in current guidelines, attempting to conceive, pregnancy and nursing are contraindications for biologics.17


However, many data have


been published on biologics in pregnancy. The Medical Board of the National Psoriasis Foundation has published consensus recommendations on treatment options in pregnant patients. TNF inhibitors, including adalimumab, etanercept and infliximab,


may be used with caution in the second and third trimesters, with relative confidence in selected patients with appropriate counselling of risks and benefits. For ustekinumab, fewer data are available. Large population-based studies and long-term data are lacking.18


Comorbidities do play a major role in selecting a conventional systemic treatment but not specifically for selecting a biologic. All biologics have similar contraindications.17 In patients with latent tuberculosis (TB), ustekinumab may be preferred, as incidences of TB reactivation appear to be lower with anti IL-12/23 inhibition.19


Combination treatment


Some combination treatments may enhance the efficacy of systemic agents and accelerate the onset of disease remission. Moreover, combination therapy may permit dose reductions of individual systemic agents, prevent antibody formation or prolong treatment intervals, so that side effects can be minimised. There is a high level of evidence that short-term treatment combining etanercept with methotrexate has better efficacy than does monotherapy with etanercept.20,21


There is some evidence that


UVB may enhance the efficacy of etanercept and ustekinumab.22,23


However, UV is


considered a contraindication for biologics.1,17


UV in combination with


biologics might enhance photocarcinogenesis. Acitretin combined with etanercept does not appear to be more favourable than monotherapy with etanercept.24


insufficient evidence on combination therapy.


Adverse events are increased in the combined treatment groups. In the short-term trials, they were mild for both the mono- and combined treatments groups. For long-term continuous disease


control, a biologic with the best benefit–risk ratio should be selected. Drug survival data25 and maintenance treatment data26


are


important in this perspective. Additionally, cost effectiveness data27,28 may be important in selecting a biologic. Eligibility and reimbursement criteria play a role. Also, clinical research/trials that have been or are being performed at the treating hospital have an impact on the selection of a biologic.


On a physician and practice level, the experience in treating psoriasis with biologics and available facilities, for example for giving infusions, do play a role. In some countries, to reduce costs, hospital pharmacists conclude contracts


with the pharmaceutical industry. The purpose of these contracts is to obtain discounts. These contracts may affect the choice of a biologic. Last but not least, shared decision- making is crucial and therefore patient preferences play an important role. They are based on many aspects, including previous experiences with drug treatment, lifestyle, mode and frequency of administration of the biologic and information received about efficacy and safety. Self-administration of biologics (adalimumab, etanercept and ustekinumab) with subcutaneous injections is often preferred over in-hospital infusions (infliximab).


Umar et al have published a study assessing the extent to which matching physicians’ treatment recommendations to patients’ treatment preferences is associated with improvement in treatment satisfaction in patients with moderate-to-severe psoriasis. Dissatisfaction with treatment is common among those with psoriasis. An approach based on preference matching showed an increase in patients’ satisfaction in the management of psoriasis.29


Lecluse et al


summarised the evidence of patient preferences and concluded that the evidence is limited and that, overall, we cannot rank therapies based on patient preferences yet.30


Switching is worth a try For the other biologics, there is


Many aspects related to switching between biologics are described in a consensus meeting report.31


Patients with ineffectiveness or loss of efficacy for one anti-TNF can benefit from a switch to another anti-TNF.3,32-36 Historically, etanercept has mostly been used as first-choice biologic in clinical practice. In a cohort of 122 patients (2005–2008), 20% of the patients switched to a second biologic (21 due to loss of efficacy, four due to safety issues). Patients switched to efalizumab* and adalimumab. Unsatisfactory response to one biologic did not predict the response to another (anti-TNF) biologic.32


data analyses showed that adalimumab seems to be an effective and safe treatment option for patients with psoriasis who failed on etanercept treatment, irrespective of the reason for discontinuation.33


In a


comparison study of treatment responses to ustekinumab in patients previously treated with TNFa inhibitors and anti-TNFa-naïve patients, lack of response to previous anti-TNF treatment does not impair clinical response to ustekinumab.34


www.hospitalpharmacyeurope.com


In 2010, daily practice


29


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