TÓPICOS GENERATIVOS
4.5 Centros de Interés integrados al currículo
Biological therapies, or biologics, are agents that are extracted or semi-synthesised from biological sources and which are used for treating specific medical conditions, including autoimmune diseases. They are frequently produced using recombinant deoxyribonucleic acid (DNA) technology and are designed to act on specific parts of the human immune system. For example, biologics such as certolizumab, etanercept (Enbrel®, Pfizer, New York, NY, USA), adalimumab (HUMIRA®, AbbVie, Maidenhead, UK), infliximab (Remicade®, Janssen Biotech, Inc., Horsham, PA, USA) and golimumab (Simponi®, Janssen Biotech, Inc., Horsham, PA, USA) block tumour necrosis factor alpha (TNF-α), and ustekinumab (STELARA®, Janssen Biotech, Inc., Titusville, NJ, USA) and secukinumab (Cosentyx®, Novartis, Basel, Switzerland) inhibit IL-12/IL-23 and IL-17-A respectively. Such biologics are indicated for a range of conditions, including psoriasis, psoriatic arthritis, rheumatoid arthritis, ankylosing spondylitis and inflammatory bowel disease.
Three biologics (adalimumab, etanercept and ustekinumab) have regulatory approval for the treatment of plaque psoriasis in children and young people (Table 1).
Adalimumab is a fully human immunoglobulin G1 monoclonal antibody that inhibits the activity of TNF-α.
It has a marketing authorisation in the UK for treating severe chronic plaque psoriasis in children and adolescents from 4 years of age who have an inadequate response to, or who are inappropriate candidates for, topical therapy and phototherapies.
Etanercept is a recombinant human TNF-αreceptor fusion protein that inhibits the activity of TNF-α. It has
a marketing authorisation in the UK for treating chronic severe plaque psoriasis in children and adolescents from the age of 6 years who are inadequately controlled by, or who are intolerant to, other systemic therapies or phototherapies.
TABLE 1 Summary of drug properties and marketing authorisations
Treatment
Age
range Disease status
Mechanism
of action Dose/frequency Treatment pathway
Adalimumab ≥4 years Severe chronic plaque psoriasis
TNF-α
inhibitor
0.8 mg/kg up to a maximum of 40 mg at weeks 0 and 1, then every 2 weeks thereafter
When topical therapy and phototherapies are inadequate or inappropriate Etanercept ≥6 years Severe chronic
plaque psoriasis TNF-α inhibitor 0.8 mg/kg up to a maximum of 50 mg weekly for up to 24 weeks
When systemic therapies or phototherapies are inadequate or not tolerated Ustekinumab ≥12 years Moderate to
severe plaque psoriasis
IL-12/IL-23 inhibitor
0.75 mg/kg for body weight of<60 kg, 45 mg for body
weight of 60–100 kg and 90 mg for body weight of
>100 kg at weeks 0 and 4,
then every 12 weeks thereafter
When systemic therapies or phototherapies are inadequate or not tolerated
BACKGROUND
NIHR Journals Library www.journalslibrary.nihr.ac.uk
Ustekinumab is a fully human monoclonal antibody that acts as a cytokine inhibitor by targeting IL-12 and IL-23. It has a marketing authorisation for treating moderate to severe plaque psoriasis in adolescent patients from the age of 12 years who are inadequately controlled by, or who are intolerant to, other systemic therapies or phototherapies.
More recently, versions of biological drugs have become available that have been manufactured after the expiry of an original innovator agent’s patent. These‘biosimilars’are developed to be highly similar to the existing biological agents in physicochemical and biological terms and are typically cheaper than the original agents. Biosimilar medicines are usually licensed for all indications specified in the licence of the originator biological medicine, but this requires appropriate scientific justification on the basis of demonstrated or extrapolated equivalence. Benepali®(Biogen Idec Ltd, Maidenhead, UK), a biosimilar of etanercept, has been approved in Europe for use in adults with moderate to severe rheumatoid arthritis, psoriatic arthritis, severe ankylosing spondylitis, severe non-radiographic axial spondyloarthritis and moderate to severe plaque psoriasis. Currently, three biosimilars of infliximab (Inflectra®, Pfizer; Remsima, Pfizer; and Flixabi®, Biogen, Cambridge, MA, USA) are approved for use in ankylosing spondylitis, Crohn’s disease, psoriatic arthritis, psoriasis, rheumatoid arthritis and ulcerative colitis.
DOI: 10.3310/hta21640 HEALTH TECHNOLOGY ASSESSMENT 2017 VOL. 21 NO. 64
© Queen’s Printer and Controller of HMSO 2017. This work was produced by Duarteet al.under the terms of a commissioning contract issued by the Secretary of State for Health. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.
Chapter 2
Definition of the decision problem
A
ccording to NICE guideline CG153 in England,11psoriasis patients are treated in three stages. First-line therapy includes traditional topical therapies (such as corticosteroids, vitamin D and vitamin D analogues, dithranol and tar preparations). Second-line therapies include the phototherapies NBUVB light and PUVA and systemic non-biological agents such as ciclosporin, methotrexate and acitretin. Systemic biological therapies such as the TNF antagonists adalimumab, etanercept and infliximab and the monoclonal antibody ustekinumab, which targets IL-12 and IL-23, can be provided as third-line therapy.The three biologics that have regulatory approval for the treatment of plaque psoriasis in children and young people (adalimumab, etanercept and ustekinumab) have not yet been appraised by NICE and no NICE technology appraisal (TA) guidance is available for treating children and adolescents in the UK with these treatments for this indication.
Objective
The aim of this study was to determine the clinical effectiveness and cost-effectiveness of adalimumab, etanercept and ustekinumab within their respective licensed indications for the treatment of plaque psoriasis in children and young people.
Note
This report contains reference to confidential information provided as part of the NICE appraisal process. This information has been removed from the report and the results, discussions and conclusions of the report do not include the confidential information. These sections are clearly marked in the report.
DOI: 10.3310/hta21640 HEALTH TECHNOLOGY ASSESSMENT 2017 VOL. 21 NO. 64
© Queen’s Printer and Controller of HMSO 2017. This work was produced by Duarteet al.under the terms of a commissioning contract issued by the Secretary of State for Health. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.