Clinical dermatology • Review article
What’s new in psoriasis? An analysis of guidelines and systematic reviews published in 2009–2010
Conflict of interest: All authors work in the UK National Health Service (NHS), which funds NHS Evidence. RBW has acted as a consultant and/or speaker for Abbott, Janssen Cilag, Leo Pharma, Pfizer and Schering-Plough, all of which manufacture therapies used in the treatment of psoriasis. CEMG has received research support and/or has acted as a consultant or lecturer for Abbott, Amge, Biogen-IDEC, Centocor, Essex Pharma, Galderma, Janssen-Cilag, Leo Pharma, Novartis, Novo Nordisk, Schering-Plough, Merck-Serono, Stiefel, UCB Pharma, Wyeth and BioTest.
A similar and more detailed review to the material published here appeared in the 2010 Annual Evidence Update on Psoriasis published by NHS Evidence website http://www.evidence.nhs.uk/ and explicit reference is given to that fuller version throughout. There are no copyright issues with using material from that source.
Dr Amy Foulkes, Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, University of Manchester, Manchester, M6 8HD, UK
This review summarizes key clinical findings from 5 guidelines and 21 systematic reviews on psoriasis published or indexed in the period November 2009 to October 2010. The highlights include the British Association of Dermatologists guidelines on the use of biological interventions in psoriasis, and guidelines on the efficacy and use of acitretin. Biological therapies were reviewed for use in specific patient groups (such as those with hepatitis C) and from a health-economics perspective. Another systematic review focused on outcome measures used to assess the severity of psoriasis. Finally, comorbidities including cardiovascular risk were the topic of four systematic reviews.
This review summarises key findings from 5 guidelines and 21 systematic reviews on psoriasis, which were indexed in bibliographic databases between November 2009 and October 2010, and included in the 2010 Annual Evidence Update on Psoriasis from NHS Evidence – skin disorders. The aim is to pick out clinically important points with the busy clinician in mind. Readers are encouraged to view the full report and original papers cited in the 2010 Annual Evidence Update (http://www.library.nhs.uk/skin/ViewResource.aspx?resID=390037&tabID=289&catID=8398), where the methods and omitted citations are given. This review considers guidelines and systematic reviews only, as they are generally considered to be the most reliable evidence base for clinical practice. Reviews summarising previous Annual Evidence Updates on psoriasis have been published previously in this journal.1,2
The British Association of Dermatologists (BAD) published guidelines for biological interventions for psoriasis in 2009.3 Patients with psoriasis may be considered eligible to receive treatment with any of the four licensed biological interventions when they fulfil specific eligibility criteria comprising: (i) severe clinical disease, defined as Psoriasis Area Severity Index (PASI) of ≥ 10 and Dermatology Life Quality Index (DLQI) of ≥ 10; and (ii) a clinical category of disease for which (a) phototherapy and alternative standard systemic therapy are contraindicated, (b) there is intolerance to standard systemic therapy, or (c) there is lack of response to standard systemic therapy. An adequate response to treatment was defined as either ≥ 50% reduction in baseline PASI (PASI50) and a decrease of ≥ 5 points in DLQI, or a ≥ 75% reduction in baseline PASI (PASI75).
The guidelines serve as a vital resource for information on the initiation and use of biological therapies in a variety of clinical scenarios, e.g. relevant screening, chronic viral infections and use in pregnancy.
It is interesting to note that the BAD guidelines did not distinguish different eligibility criteria for infliximab, as is the case with guidance from the National Institute for Health and Clinical Excellence (NICE),4 which states that to qualify for this particular drug, a patient needs very severe disease (PASI of 20 and DLQI of 18). At the time of that publication, adalimumab or etanercept were considered first-line biologicals, with ustekinumab being reserved as a second-line agent and infliximab advised when more rapid disease control is required. As with any guidelines, it is important to consider literature published after the guidelines; for example, as greater long-term safety data emerge for ustekinumab, this may in time alter its positioning.
The BAD also published guidelines on the efficacy and use of acitretin in 2010.5 Already a popular second-line systemic agent in the treatment of severe psoriasis, the guidelines reviewed evidence for its use in all dermatological disease. Acitretin monotherapy was recommended in the treatment of severe psoriasis, palmoplantar pustulosis, hyperkeratotic hand eczema, severe Darier’s disease (keratosis follicularis), severe congenital ichthyosis, and keratoderma. Evidence was presented that the conditions benefiting from the antimitotic and keratolytic actions of acitretin include lichen planus, lichen sclerosus, discoid lupus erythematosus, and prevention of cutaneous malignancies in recipients of organ transplants. Preliminary investigations required before starting acitretin were summarized, and a detailed monitoring process was provided.
National Health Service Clinical Knowledge Summaries (CKS; formerly PRODIGY) are a source of evidence-based information and practical knowledge about the common conditions managed in primary care. The new CKS Psoriasis topic6 is a thorough resource that could prove useful to both patients and healthcare professionals. It includes a useful lay summary (which can alternatively be viewed as a patient-information leaflet) and a detailed guide to psoriasis management in primary care, which links to the supporting evidence.
The American Academy of Dermatology has produced guidelines on the use of phototherapy for the treatment of psoriasis.7 Although an extensive review of literature has been summarized, prescriptive protocols are used, and these do not reference essential dosimetry and calibration, unlike the 2002 British Photodermatology Group guidelines.8
Severity and outcome measures
A systematic review of the best outcome measures for assessing plaque psoriasis severity suggests that the PASI is the most extensively studied clinical severity score and also the most thoroughly validated according to methodological criteria.9 The same criteria were also used to assess outcome measures of quality of life in plaque psoriasis, with the conclusion that the DLQI is the easiest to use in clinical practice.10
Mounting evidence for an association between cardiovascular disease (CVD) and severe psoriasis was found in a review of 14 studies on this topic,11 concluding that there is a ‘substantial’ increased risk of CVD in patients with both psoriasis and psoriatic arthritis (PsA).
An increased risk for both obesity and metabolic syndrome was found by Prey et al.12 in their review of 18 cross-sectional case–control studies of patients with solely plaque-type psoriasis. Bremmer et al.13 published a review on obesity and psoriasis, which concluded that the amount of category I evidence for objectively determining the best treatment choices for obese patients with psoriasis was scarce, considering the relative risk associated with therapeutic options in those with obesity as a comorbidity.
An investigation of the prevalence of psoriasis in multiple sclerosis14 found conflicting data from an evaluation of 19 articles. Despite the previous hypothesis that these diseases may be associated because of common immunopathogenic factors such as the dysregulation of the T-helper (Th)17 cell pathway, it was concluded that an association could not be established from published literature.
Estimates of the prevalence of PsA in psoriasis vary widely, in the range 5–40%.15 The time to development of PsA in patients with plaque psoriasis also remains unclear. A review of eight epidemiological studies by Prey et al.16 suggested a prevalence of 7–26% on examination using rheumatologically validated criteria.
There are few evidence-based data to guide clinicians in managing the challenge of erythrodermic psoriasis. Rosenbach et al.17 evaluated the therapeutic options available, and suggested that the paucity of high-quality scientific data indicated a need for dedicated clinical trials. However, these authors searched only PubMed, so some trials might have been missed in other databases such as EMBASE.
Therapies for psoriasis in specific patient groups
Frankel et al.18 reviewed the treatment of patients with psoriasis with concomitant hepatitis C virus (HCV), an important issue, as interferon-α can trigger and/or worsen psoriasis. Data indicate that ciclosporin A can contribute to a good outcome in patients with psoriasis and concomitant HCV, in terms of both safety and efficacy. The authors noted that further investigations of safety are required. Acitretin, psoralen ultraviolet A and anti-tumour necrosis factor-α agents were suggested as second-line agents.
For patients with psoriasis and concomitant human immunodeficiency virus (HIV) infection, treatments have been considered by a task force of the US National Psoriasis Foundation Medical Board.19 Acitretin was proposed as a safe second-line agent. Interestingly, biologicals have been used in series of patients with both HIV and rheumatoid arthritis, with some success. It was reinforced that this approach should be reserved for those with debilitating disease, and should remain a joint management decision with specialists in infectious diseases.
A study on economic factors in the use of biological agents used pharmacoeconomic analyses with numerous limitations, as drug toxicity and long-term efficacy were not taken into account.20
Evidence Review Group report summaries were produced for NICE by Gospodarevskaya et al. on the use of ustekinumab to treat moderate to severe psoriasis21 and by Turner et al. for adalimumab.22 The resulting NICE guidance stated that ustekinumab is recommended as a treatment option for adults with severe plaque psoriasis (PASI ≥ 10; DLQI ≥ 10) unresponsive to standard systemic therapy,23 and adalimumab as a treatment option for adults with severe plaque psoriasis (PASI ≥ 10; DLQI ≥ 10) unresponsive to standard systemic therapy.24
In conclusion, systematic reviews over the last year have once again focused on the use of biologicals for the treatment of psoriasis, although this has now been expanded to their use in subgroups of patients such as those with viral or retroviral disease. In the current economic climate, we may expect to see further pharmacoeconomic analyses of the use of biological therapies.
- • The BAD has published guidelines on the use of biologicals in psoriasis. Recommendations include the use of ustekinumab in patients who fulfil the stated disease criteria, and for whom TNF antagonist therapy has failed or is contraindicated.
- • The BAD has published guidelines on the use of acitretin; recommended monitoring includes assessment of liver enzymes and fasting serum cholesterol and triglycerides every 2–4 weeks for the first 2 months of treatment, and then every 3 months.
- • PASI remains the best-validated outcome measure for assessing chronic plaque psoriasis, although its weaknesses include its poor sensitivity at the lower end of the scale.
- • The relationship between cardiovascular risk and chronic plaque psoriasis is complex, and a true association remains to be established.
- • There are few evidence-based data to guide clinicians in the management of erythrodermic psoriasis.
AF is a Clinical Research Training Fellow funded by the North-west England Medical Research Council Clinical Research Training Fellowship in Clinical Pharmacology and Therapeutics. CEMG is supported in part by the National Institute for Health Research (NIHR) Manchester Biomedical Research Centre. RBW is an NIHR Senior Clinical Lecturer.
The purpose of this activity is to review new guidelines and systematic reviews on psoriasis published or indexed from November 2009 to October 2010 and to demonstrate up-to-date knowledge on psoriasis.
Which of the following dermatological diseases would you consider treating with oral acitretin, according to the British Association of Dermatologists guidelines on its use?
a) Severe psoriasis
b) Mild atopic eczema
c) Acne vulgaris
d) Viral warts
e) Basal cell carcinoma
Which is the most studied outcome measure for assessing the severity of chronic plaque psoriasis?
The National Institute of Health and Clinical Excellence issued guidance that ustekinumab was indicated in patients with which combination of the following scores?
a) PASI > 5; DLQI > 10
b) PASI > 10; DLQI > 10
c) PASI ≥ 10; DLQI ≥ 10
d) PASI > 20; DLQI > 10
e) PASI ≥ 20; DLQI ≥ 10
Which of the following treatments is known to trigger/worsen psoriasis in patients with concomitant viral hepatitis?
Which of the following statements is recommended in US guidelines as best management for patients with severe psoriasis and human immunodeficiency virus infection?
a) Patients should always be managed with anti-tumour necrosis factor-α therapy
b) Patients should be jointly managed by a dermatologist and a specialist in infectious diseases
c) Patients should be admitted for inpatient treatment
d) Patients should always be treated with ustekinumab
e) Phototherapy is the best option
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