Special supplement

Prescribing information can be found on the inside back cover

Winter 2012

MODERATE-TO-SEVERE PSORIASIS

Initiated, funded and reviewed by

1.5creditsCPD

2

CONTENTS AND INTRODUCTION

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Published by Haymarket Medical, 174 Hammersmith Road, London W6 7JP.Senior project editor: Joanne Taylor; Managing editor: Hannah Cottle; Editor of MIMS Dermatology: Paula Hensler; Producer: Stephanie Jackson; Commercial director: Sandie Pears; Project manager: Lindsay Aldridge; Group art editor: Pauline Lock; Deputy production manager: Lucy Flatman; Head of delivery: Katie McCormack; Senior commercial director: Clair McHale; Medical director: Robert Brines; Medical education director: Richard Yarwood; Director: Jenny Gowans. The views expressed in this publication are those of the authors and not necessarily those of Haymarket Medical or Janssen. Readers are advised to make their own further enquiries of manufacturers or specialists in relation to particular drugs, treatments or advice. The publishers and printers cannot accept liability for errors or omissions. No part of this publication may be reproduced in any form without the written permission of the publisher, application for which should be made to the publisher.©2013 Haymarket Medical Media Ltd. Date of preparation: November 2012 (revised April 2013); PHGB/STE/1112/0755b

OPINION3 TheroleofGPsinthemanagementof

moderate-to-severepsoriasisDr Brian Malcolm

FEATURE4 Diagnosisandmanagementof

moderate-to-severepsoriasisDr Rebecca Ellard and Dr Anshoo Sahota

FEATURE6 Achievinglong-termcontrolof

moderate-to-severepsoriasisDr Amy Foulkes and Dr Richard Warren

CASE STUDY8 Apatienttreatedwithustekinumab

Dr Alia Ahmed and Dr Anthony Bewley

OPINION9 NICEguidelineontheassessmentand

managementofpsoriasisDr David Chandler and Dr Anthony Bewley

MANAGEMENT ALGORITHM10 Diagnosisandmanagementof

moderate-to-severepsoriasisDr Justine Kluk, Dr Shantini Rice, Dr Sandy McBride and Professor Malcolm Rustin

INTRODUCTIONPsoriasis is a chronic skin condition that can have a marked physical and psychological impact on those affected. While most patients have mild disease that can be managed in primary care, those with moderate-to-severe psoriasis require referral for specialist inter-vention and access to therapy such as biologics.

Biologics are an option for patients who have failed to respond to standard systemic ther-apy or in those for whom systemic therapy is unsuitable. The scope of this supplement is to enhance the understanding of biologics.

Dr Brian Malcolm provides his opinion on the role of the GP in the management of moderate -to-severe psoriasis.

Dr Rebecca Ellard and Dr Anshoo Sahota discuss the key elements of the diagnosis and management of moderate-to-severe psoriasis.

Dr Amy Foulkes and Dr Richard Warren focus on long-term control of psoriasis.

Dr Alia Ahmed and Dr Anthony Bewley present a case of a patient who was success-fully treated with biologics.

Dr David Chandler and Dr Anthony Bewley provide a summary of the recently published NICE guideline on psoriasis.

Dr Justine Kluk, Dr Sandy McBride and Professor Malcolm Rustin present a manage-ment algorithm to aid the diagnosis, treatment and referral of patients with moderate-to-severe psoriasis

Dr Paula Hensler, Editor, MIMS Dermatology

3

Psoriasis is common, affecting approximately 2% of the UK population.1 Such prevalence demands that a GP should have an up-to-date knowledge of this condition, specifically the potential triggers, the treatments available and when to refer patients to secondary care.

PHYSICAL AND PSYCHOLOGICAL DISTRESSPsoriasis can be very distressing.2 Patients can be significantly disabled by plantopalmar pus-tular psoriasis, severe scalp psoriasis, fissuring hyperkeratotic psoriasis of the hands, or rarely, acropustulosis. Genital involvement can also lead to high levels of sexual distress.3 GPs are well placed to offer support and manage patient expectations about treatment outcomes.

RECOGNISING TRIGGERSGPs should understand the pathogenesis of the psoriasis to avoid exacerbations with the use of prescribed drugs known to potentially worsen psoriasis. These include lithium, anti-malarials and beta-blockers.4 GPs can also offer advice regarding exacerbating lifestyle factors such as alcohol, stress and smoking,4 especially as there is a growing recognition that psoriasis is an independent risk factor for cardiovascu-lar disease.5

TREATMENT KNOWLEDGEIt is important that GPs have a good understand-ing of topical treatments. GPs must also be aware that certain topical treatments, particularly ster-oids, may have systemic effects if they are used long term.4 Furthermore, the usefulness of simple emollients to keep skin hydrated should never be underestimated.4 Even if a patient is

under specialist care, the GP still has a pivotal role in repeat prescribing and shared-care plans.

SECOND-LINE TREATMENTSGPs should have understanding of the patient’s individual needs. Furthermore, there should be an awareness of commonly used second-line drugs and their implications, for example, family planning issues with the use of retin-oids,4 alcohol intake with methotrexate,4 renal function, hypertension and a history of cancer with ciclosporin4 and a past history of infections, particularly TB, and cancer with biologics.6

REFERRAL TO SECONDARY CAREReferral should be considered when there is diag-nostic doubt; when topical treatments have failed; in extensive disease and where there are difficult treatment sites. Erythrodermic or generalised pustular psoriasis also warrant referral, as does severe arthropathy. GPs have an important role in writing relevant and precise referral letters.

Even when a patient requires specialist care, there is potential for a knowledgeable GP to con-tribute to a holistic management approach.

Dr Brian Malcolm is associate specialist, GP principal and GPSI in dermatology in Barnstaple, Devon

REFERENCES1. Eedy DJ, Griffiths CEM, Chalmers RJG et al. Care of patients

with psoriasis: an audit of UK services in secondary care. Br J Dermatol 2009; 160:557–64.

2. Krueger G, Koo J, Lebwohi M et al. The impact of psoriasis on quality of life: Results of a 1998 National Psoriasis Foundation patient memebership survey. Arch Dermatol 2001 :137:280-4

3. Meeuwis KA, de Hullu JA, van de Nieuwenhof HP et al. Quality of life and sexual health in patients with genital psoriasis. Br J Dermatol 2011; 164:1247-55.

4. Menter A, Griffiths CEM. Current and future management of psoriasis. Lancet 2007;370:272-84.

5. Ahlehoff O. Psoriasis and cardiovascular disease: epidemiological studies. Dan Med Bull. 2011; 58:B4347.

6. MIMS. November 2012.

GPs have a pivotal role in managing this condition, says Dr Brian Malcolm.

The role of GPs in the management of moderate-to-severe psoriasis

OPINION

4

FEATURE

Psoriasis is a chronic disease that affects approxi-mately 1-3% of the population,1 with or without psoriatic arthritis. Patients typically present with ‘unsightly’ lesions which are sometimes itchy; for many there is no identifiable cause. Psoriasis can have a profound effect on quality of life and is also associated with cardiovascu-lar disease.2 Recent NICE guidance states that management should include early and continual assessment of psoriasis from first presenta-tion in primary care through to specialist care. The guidance focuses on disease severity, phys-ical and psychological effect, assessment for referral and treatment choice.2

ASSESSMENT OF PSORIASISVarious tools can be used to measure physi-cal severity or functional severity of psoriasis. Physical severity is categorised as clear, mild, severe or very severe, as outlined in the Physicians’ Global Assessment (PGA) or more precisely with the Psoriasis Area and Severity Index (PASI).3 Doctors should also note when nails, face, scalp or genitals are affected as these are particularly difficult to treat, along with symptoms or signs of psoriatic arthritis.

The PASI divides the body into head, arms, trunk and legs and notes the amount of redness, thickness and scale, along with percentage of area affected. A score maximum of 72 is given, and can help assess a patient’s response to treat-ment pre- and post intervention. The majority of patients will have mild disease (<3% body affected) which can be successfully managed

with topical therapy.4 More extensive disease (>10% body affected or PASI score >12) usually needs specialist input.

Functional severity can be measured with quality-of-life tools such as the Dermatology Life Quality Index (DLQI).5 Psychological morbidity is not well represented with these tools, but can be an important marker for dis-ease impact. NICE guidelines suggest assessing impact on daily living, ability to cope with the treatment regimen, change in mood and impact on family or carers.2

STEPWISE APPROACH TO MANAGEMENT Management of chronic illness such as psoria-sis should include physical and psychological aspects.2 It is helpful to manage expectations at an early stage and allow the patient control over their treatment, particularly with topical ther-apy. There is often the need to combine topical and systemic treatments.

The first step is topical treatment including the daily use of emollients. Patients should be reassured that almost any emollient is useful even if not prescribed or ‘dermatological’ in nature. Most patients will also need intermit-tent topical corticosteroid, with or without a vitamin D analogue, or a coal tar preparation.2

Management should include early and continual assessment from first presentation through to specialist care, write Dr Rebecca Ellard and Dr Anshoo Sahota

Diagnosis and management of moderate-to-severe psoriasis

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5

FEATURE

BOX1:Indicationsforspecialistreferral2

● Diagnostic uncertainty ● Psoriasis is severe or extensive, or cannot be controlled with topical therapies

● There is a need for phototherapy ● Nail involvement that has functional or cosmetic impact

● It is having a major impact on quality of life ● Patient is a child ● Patient has generalised pustular or erythrodermic psoriasis

Less commonly used products such as dithranol might be best used under specialist supervision.2

Second-line is phototherapy where narrow-band UVB has become the first choice followed by psoralen with UVA (PUVA). Some patients find the time commitment for phototherapy (typically 20-30 treatments in two-months) too onerous and will move to the third step.2

Third-line treatments, for adult patients only, include ciclosporin, methotrexate and acitretin.2 These can be very effective although side-effects, including renal and hepatic toxicity, mean that patients should be monitored by a specialist. NICE guidance suggests methotrexate as the first choice in adults with moderate-to-severe psoria-sis where topical therapies and phototherapy have not worked and where there is functional impair-ment and high levels of distress. Where psoriatic arthritis is present, a systemic agent should be chosen in discussion with a rheumatologist.2

Adults with moderate-to-severe psoriasis who have failed to respond to, or cannot tolerate two systemic drugs should be offered the fourth step of biological agents including TNF-antagonists such as adalimumab, etanercept and infliximab, and an anti-IL-12/23 monoclonal antibody such as ustekinumab. These drugs are generally well tolerated in the majority of people.2

TRIGGERS AND ASSOCIATIONS In a newly-diagnosed patient, it is important to consider triggers, such as a streptococcal infection causing guttate psoriasis.6 Patients should be asked about common triggers such as high alcohol intake and stress, as it may be possible to prevent the use of systemic agents by avoiding such triggers. A specific trigger for palmoplantar pustular psoriasis is cigarette smoking (especially in women in their fourth or fifth decade of life) so patients should be made aware of this association.7

FLARESWhen psoriasis flares it can mean there is more of the disease or, less commonly, it can indi-cate the disease has become unstable and may

become a systemic problem. In these patients specialist input should be sought.2 An inpatient stay may be necessary, particularly if the pso-riasis is unstable. Traditional treatments such as bed rest and bland emollients can be help-ful and rapidly working systemic agents such as ciclosporin may be useful in the short-term until the flare settles.

With the increasing recognition of the health, economic and psychological burden of psoriasis, the recent NICE guidance is a helpful resource. With the knowledge of a few simple principles of management, psoriasis can be gratifying to treat.

Dr Rebecca Ellard is a foundation doctor and Dr Anshoo Sahota is a consultant dermatologist, Barts Health NHS Trust

REFERENCES1. Naldi L, Griffiths CEM. Traditional therapies in the management

of moderate to severe chronic plaque psoriasis: an assessment of the benefits and risks. Br J Dermatol 2005; 152:597-615.

2. NICE. Guidance on the assessment and management of psoriasis. CG153. London, NICE, 2012. Available from www.nice.org.uk/CG153

3. PASI. What is PASI? PASI training. 2008. Accessed 15th November 2012. Available from: http://pasitraining.com/index.html.

4. Kurd SK and Gelfand JM. The prevalence of previously diagnosed and undiagnosed psoriasis in US adults: results from NHANES 2003-2004. J Am Acad Dermatol 2009; 50: 891-5.

5. Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI)-a simple practical measure for routine clinical use. Clin Exp Dermatol 1994; 19:210-6.

6. Owen CM, Chalmers RJG, O’Sullivan T et al. A systematic review of antistreptococcal interventions for guttate and chronic plaque psoriasis. Br J Dermatol 2001; 145:886-90.

7. Poikolainen K, Reunala T, Karvonen J. Smoking, alcohol and life events related to psoriasis among women. Br J Dermatol 1994; 130:473-7.

6

FEATURE

The management of psoriasis can be interest-ing and rewarding. Optimal use of psoriasis treatments can lead to a vast improvement in a patient’s quality of life. It is, however, impor-tant to be honest with patients and explain that treatment is non-curative but aims to allow regression of psoriasis plaques to normal- looking skin. Whilst guidelines exist for the various severities of psoriasis, treatment options should be tailored to the individual. This review will briefly discuss new guidance and newer therapies in the treatment of severe psoriasis.

TIMELY REFERRALNICE have recently published guidelines on the management of psoriasis from primary through to tertiary care.1 Useful elements for the primary care physician include referral recommenda-tions for specialist advice where:

● psoriasis is severe or extensive, for example more than 10% of body surface area (BSA; the size of the palm is approximately 1% BSA)

● there is diagnostic uncertainty ● psoriasis cannot be controlled with topical therapy

● there is acute guttate psoriasis that requires phototherapy

● nail disease has a major functional or cosmetic impact

● where any type of psoriasis is having a major impact on a person’s physical, psychological or social wellbeing.

NICE additionally recommend using a rec-ognised questionnaire, such as the Psoriasis

Epidemiology Screening Tool (PEST)2 to screen for the presence of psoriatic arthritis (PsA).

BIOLOGICSThe major advance in the management of severe psoriasis in the past decade has been the introduction of injectable biologic therapies, of which there are two approved groups in the treatment of psoriasis: TNF inhibitor agents (adalimumab, etanercept and infliximab) and those inhibiting interleukins (IL)-12 and IL-23 (ustekinumab).

Strict eligibility criteria are applied for use of all biologics, including:1

● history of chronic psoriasis (more than six months);

● documented failure or unsuitability for traditional systemic therapies and phototherapy and;

● physical severity and quality of life detriment above a certain threshold.

RCTs have shown that TNF inhibitors are a good therapeutic option for PsA3-6 and etaner-cept is now approved for the management of severe psoriasis in children.7

EVIDENCE BASEThe most recent biologic in use is ustekinumab, a fully humanised monoclonal antibody to the p40 subunit, common to IL-12 and IL-23. Large RCTs have demonstrated that ustekinumab is effective in psoriasis with a rapid onset of action and high response rates.8-10 The Psoriasis Area Severity Index (PASI) is a validated composite score of psoriasis severity, where a 75% improve-ment from baseline score is termed a PASI 75 response. In a RCT of 1,230 patients with moder-ate to severe psoriasis, 67% of patients receiving a 45mg dose and 76% of those receiving a 90mg

An appreciation of newer therapies is crucial, say Dr Amy Foulkes and Dr Richard Warren

Achieving long-term control of moderate-to-severe psoriasis

7

FEATUREiS

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Treatmentaimstoregresspsoriasisplaques

dose reached a PASI 75 at week 12, compared with 4% of those receiving placebo.9 After dose loading, ustekinumab is injected every 12 weeks. These short-term data are impressive and are supported by significant improve-ments in patient quality of life. Ustekinumab was generally well tolerated, without evidence of cumulative toxicity with increased duration of exposure.

However, extensions of clinical trials are not able to tell the full story about the safety of a therapy as any clinical trial has significant selection bias in the first instance. Thus, further safety data on all biologic therapies will come from large-scale registries that capture key data from those patients commencing systemic and biologic therapies. One of the best registries worldwide is being conducted in the UK, the British Association of Dermatologists’ (BAD)

Biologic Interventions Register (BADBIR). Thus far, more than 3,500 biologic patients and 2,000 systemic patients have been recruited to BADBIR.

Whilst the majority of patients will have mild disease that can be managed effectively in pri-mary care, an appreciation of newer therapies is crucial, as these can be life changing for those with severe disease.

Dr Amy Foulkes is dermatology specialist registrar and Dr Richard Warren is NIHR Senior Clinical Lecturer and Honorary Consultant Dermatologist, Salford Royal NHS Foundation Trust.

REFERENCES1. NICE. Guidance on the assessment and management of

psoriasis. CG153. London, NICE, 2012. Available from: www.nice.org.uk/CG153

2. Ibrahim GH, Buch MH, Lawson C et al. Evaluation of an existing screening tool for psoriatic arthritis in people with psoriasis and the development of a new instrument: the Psoriasis Epidemiology Screening Tool (PEST) questionnaire. Clin Exp Rheumatol 2009; 27:469-74.

3. Gladman DD, Mease PJ, Ritchlin CT et al. Adalimumab for long-term treatment of psoriatic arthritis: forty-eight week data from the adalimumab effectiveness in psoriatic arthritis trial. Arthritis Rheum 2007; 56:476-88.

4. Kavanaugh A, Antoni CE, Gladman D et al. The Infliximab Multinational Psoriatic Arthritis Controlled Trial (IMPACT): results of radiographic analyses after 1 year. Ann Rheum Dis 2006; 65:1038-43.

5. Mease PJ, Gladman DD, Ritchlin CT et al. Adalimumab for the treatment of patients with moderately to severely active psoriatic arthritis: results of a double-blind, randomized, placebo-controlled trial. Arthritis Rheum 2005; 52:3279-89.

6. Mease PJ, Goffe BS, Metz J et al. Etanercept in the treatment of psoriatic arthritis and psoriasis: a randomised trial. Lancet 2000; 356:385-90.

7. Enbrel (etanercept) SPC. 2012. Available from: http://www.medicines.org.uk (accessed 29 November 2012).

8. Leonardi CL, Kimball AB, Papp KA et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1). Lancet 2008; 371:1665-74.

9. Papp KA, Langley RG, Lebwohl M et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet 2008; 371:1675-84.

10. Krueger GG, Langley RG, Leonardi C et al. A human interleukin-12/23 monoclonal antibody for the treatment of psoriasis. N Engl J Med 2007; 356:580-92.

8

Successful management of psoriasis can be challenging, write Dr Alia Ahmed and Dr Anthony Bewley

A patient treated with ustekinumab

CLINICAL HISTORYAC is a 65-year-old male with moderate-to-severe psoriasis. In the last ten years he had been trialled on a number of treatments, including hydroxy urea and methotrexate, with limited success. The patient also responded poorly to etanercept, with their Psoriasis Area Severity Index (PASI) dropping from 25 to only 22.4 over six months. A similar picture occurred with adalimumab (PASI dropping from 24 to 20.8 in six months). AC’s Dermatology Life Questionnaire Index scores (DLQI) ranged from 18 to 24 during this time. Ciclosporin was not given due to the patient’s high blood pressure.

The next step was to treat with ustekinumab (45mg 12-weekly). Within five months the PASI and DLQI scores dropped to zero, indicating disease clearance. To date, AC remains stable on ustekinumab, with no major side effects.

COMMENTTreatment of moderate-to-severe psoriasis can be challenging. Topical therapy and conventional systemic agents are not always successful and may be associated with adverse side effects. In these circumstances, treatment with biologics is necessary. TNF-alpha and the interleukins (IL-12 and 23) have been identified as therapeutic targets in psoriasis.1 Biologic agents used for treatment of psoriasis include etanercept, adalimumab, infliximab and ustekinumab.2

Ustekinumab is a monoclonal antibody directed against IL-12 and IL-23, and its efficacy has been evaluated in high-quality trials.3-5 A systematic review has suggested continuous

treatment with biologic agents to control psoriasis.2

NICE guidance has suggested initiation of ustekinumab in patients with severe psoriasis that have not responded to systemic therapy, or where there is an intolerance or contraindi-cation. The guidance also suggests treatment should be stopped at 16 weeks if there is <75% reduction in PASI or there is <50% reduction in PASI plus <5 point reduction in DLQI from baseline.6

The physician must first assess the rea-sons for non-response to treatment and rule out confounding factors such as adherence, infection, natural variation in disease and stress.1 The benefit -risk profile needs consid-eration for every patient, coupled with close monitoring.

Dr Alia Ahmed is clinical research fellow in dermatology and Dr Anthony Bewley is consultant dermatologist, Barts Health NHS Trust.

REFERENCES1. Brezinski EA, Armstrong AW. Off-label biologic regimens

in psoriasis: a systematic review of efficacy and safety of dose escalation, reduction, and interrupted biologic therapy. PLoS One. 2012;7:e33486.

2. Reich K, Burden AD, Eaton JN, Hawkins NS. Efficacy of biologics in the treatment of moderate to severe psoriasis: a network meta-analysis of randomized controlled trials. Br J Dermatol. 2012; 166:179-88.

3. Leonardi CL, Kimball AB, Papp KA et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised double-blind, placebo-controlled trial (PHOENIX 1). Lancet 2008; 371:1665-74.

4. Papp KA, Langley RG, Lebwohl M et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised double-blind, placebo-controlled trial (PHOENIX 2). Lancet 2008;371:1675-84.

5. Griffiths CEM, Strober BE, van de Kerkhof P et al. Comparison of ustekinumab and etanercept for moderate-to-severe psoriasis. N Engl J Med 2010;362:118-28

6. NICE. Ustekinumab for the treatment of adults with moderate to severe psoriasis. TA180. London, NICE, 2009. Available from: www.nice.org.uk/TA180

CASE STUDY

9

The new NICE guideline for psoriasis high-lights key priorities for implementation, with the aim of improving the delivery of care.1

ASSESSMENT AND REFERRALAll patients with psoriasis should receive a complete and holistic assessment. Assessment of severity is based on clinical examination, and the Psoriasis Area and Severity Index (PASI).2 Assessment should be tailored to the individual, and it is vital to assess health-related quality of life. A recommended tool is the Dermatology Life Quality Index (DLQI).3

The majority of patients are managed in primary care.1 Referral should be considered when there is diagnostic uncertainty, exten-sive disease, nail disease that has a functional and cosmetic impact, failure of topical treat-ments or the need for phototherapy, and where there are concerns about the patient’s wellbeing.

COMORBIDITIESPsoriasis can be complicated by arthritis in up to 30% of patients.4 The use of a validated tool, for example the Psoriasis Epidemiological Screening Tool (PEST), is recommended to assess adults. Urgent referral to a rheumatolo-gist is necessary if severe psoriatic arthritis is suspected.

Risk factors for cardiovascular disease are more prevalent in patients with psoriasis. Advice should be tailored to the individual and, where appropriate, include information about risk factor modification.

TREATMENTSPatients should be involved in all treatment decisions .Topical therapy should be offered as first-line treatment and practical advice on their use should be provided. Initial treatment for adults with psoriasis affecting the trunk or limbs should consist of a corticosteroid plus vita-min D (combination) or a vitamin D analogue.

Narrowband UVB should be considered for plaque or guttate psoriasis that is unresponsive to topical treatments.

Conventional systemic agents can be offered where topical treatments and phototherapy have failed, with extensive disease (PASI>10), or with localised disease with functional impair-ment. Methotrexate is the first choice.

Biologics can be used when other systemic agents have failed. An alternative biologic should be considered if: the psoriasis does not respond to a first biologic (at 10 weeks for infliximab, 12 weeks for etanercept, and 16 weeks for adalimumab and ustekinumab); or the psoriasis improves but subsequently loses this response; or the biologic is not tolerated or is contraindicated.1

These recommendations have been incorpo-rated into a helpful ‘NICE pathway’.5

Dr David Chandler is a medical SHO and Dr Anthony Bewley is a consultant dermatologist, Barts Health NHS Trust.

REFERENCES1. NICE. Guidance on the assessment and management of

psoriasis. CG153. London, NICE, 2012. www.nice.org.uk/CG1532. PASI. What is PASI? PASI training. 2008. Accessed 15th November

2012. Available from: http://pasitraining.com/index.html.3. Finlay AY, Khan GK. Dermatology Life Quality Index

(DLQI)-a simple practical measure for routine clinical use. Clin Exp Dermatol 1994; 19:210-6.

4. Zachariae H. Prevalence of joint disease in patients with psoriasis: implications for therapy. Am J Clin Dermatol. 2003; 4(7): 441-7.

5. NICE Pathways. http://pathways.nice.org.uk/pathways/psoriasis/

NICE guideline on the assessment and management of psoriasis This new guideline recommends holistic management, say Dr David Chandler and Dr Anthony Bewley

OPINION

10

YES

efficacy, and effect of dose reduction. Br J Dermatol 2005; 152: 1304-12.

4. Reich K, Nestle FO, Papp K et al. Infliximab induction and maintenance therapy for moderate-to-severe psoriasis: a phase III, multicentre, double-blind trial. Lancet 2005; 366: 1367-74.

5. Menter A, Tyring SK, Gordon K et al. Adalimumab therapy for moderate to severe psoriasis: A randomized, controlled phase III trial. J Am Acad Dermatol 2008; 58: 106-15.

6. Papp KA, Langley RG, Lebwohl M et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet 2008; 371: 1675-84.

7. Smith C, Anstey A, Barker J et al. British Association of Dermatologists’ guidelines for biologic interventions for psoriasis 2009. Br J Dermatol 2009; 161: 987–1019.

8. Leman J, Burden AD. Sequential use of biologics in the treatment of moderate-to-severe plaque psoriasis. Br J Dermatol 2012; 167 (suppl.3): 12-20.

By Dr Justine Kluk and Dr Shantini Rice, dermatology registrars, and Dr Sandy McBride and Professor Malcolm Rustin, consultant dermatologists, Royal Free London NHS Foundation Trust.

REFERENCES1. NICE Psoriasis: Assessment and management of psoriasis.

CG153. London, NICE, 2012. www.nice.org/CG1532. SIGN Diagnosis and management of psoriasis and psoriatic

arthritis in adults.A national clinical guideline No. 121; 2010. Available from:www.sign.ac.uk/guidelines/fulltext/121/index.html.

3. Papp KA, Tyring S, Lahfa M et al. A global phase III randomized controlled trial of etanercept in psoriasis: safety,

MANAGEMENT ALGORITHM

Second-line therapies:●● Phototherapy●● Acitretin●● Methotrexate●● Ciclosporin●● Hydroxycarbamide

Topical therapies:●● Topical●steroid●● Coal●tar●● Dithranol●● ●Vitamin●D●analogues●●(+/-●topical●steroid)●

●● Calcineurin●inhibitors

DLQI●=●dermatology●life●quality●index

PASI●=●psoriasis●area●&●severity●index

CONTINUE

DISCONTINUE TREATMENTConsider●alternative●biologic●agent8

ADVERSE REACTION OR SECONDARY

TREATMENT FAILURE

NO

YES

Adequate response to biologics defined as:7

75%●reduction●in●PASI●score

OR50%●reduction●in●PASI●

score

AND5-point●reduction●in●DLQI

(Assess infliximab at week 10, etanercept at week 12, adalimumab and ustekinumab at week 16 from when treatment started)

Emergency referral if:Erythrodermic●or●

generalised●pustular●psoriasis2

*Following appropriate history, examination and

screening tests:eg●hepatitis●and●HIV●serology,●

tuberculosis●risk●factors,●previous●or●current●malignancy7

CONTINUE

PSORIASIS DIAGNOSISAssess●severity:1●

Mild●=●PASI/DLQI●<5Severe●=●PASI●≥10/DLQI●>10

Consider●comorbidities●such●as●cardiovascular●disease,●psoriatic●arthritis●and●patient●wellbeing

Provide●patient●information

ADEQUATE RESPONSE?7

BIOLOGICS FOR PSORIASIS*●● Etanercept3● ● Infliximab4●

●● Adalimumab5● ● Ustekinumab6

SECOND-LINE THERAPIESAdequate●response●or●no●treatment●

contraindications

REFER TO SECONDARY CARE IF:●● Failure,●or●intolerance●of●topical●therapies●● DLQI●>52

●● Nail●disease●with●functional/cosmetic●impact●●High●impact●sites●●Acute●guttate●psoriasis●requiring●phototherapy●● ●Major●impact●on●physical,●psychological●or●social●wellbeing●●Uncertainty●of●diagnosis

NO

NO

Prescribing Information

Date of preparation: February 2013 PHGB/STE/1212/0886(1)

STELARA® 45 mg solution for injection in pre-fi lled syringe PRESCRIBING INFORMATIONACTIVE INGREDIENT(S): Ustekinumab. Please refer to Summary of Product Characteristics (SmPC) before prescribing. INDICATION(S): Treatment of moderate to severe plaque psoriasis in adults who failed to respond to, or who have a contraindication to, or are intolerant to other systemic therapies including ciclosporin, methotrexate and PUVA. DOSAGE & ADMINISTRATION: Under the guidance and supervision of a physician experienced in diagnosis and treatment of psoriasis. Subcutaneous injection. Avoid areas with psoriasis. For self-injecting patients ensure appropriate training, follow-up and monitoring during treatment. Adults & Elderly: Patients ≤ 100kg, 45 mg at week 0 followed by a 45 mg dose at week 4, then every 12 weeks. Patients >100 kg, 90 mg at week 0 followed by a 90 mg dose at week 4, then every 12 weeks (45 mg was less effective in these patients). Consider discontinuation if no response after 28 weeks. Children <18 years: Not recommended. Renal & Hepatic impairment: Not studied. CONTRAINDICATIONS: Hypersensitivity to product; clinically important, active infection. SPECIAL WARNINGS & PRECAUTIONS: Infections: Potential to increase risk of infections and reactivate latent infections. Caution in patients with a chronic infection or history of recurrent infection, particularly TB. Patients should be evaluated for tuberculosis prior to initiation of STELARA. Consider anti-tuberculosis therapy prior to initiation of STELARA in patients with past history of latent or active tuberculosis. Patients should seek medical advice if signs or symptoms suggestive of an infection occur. If a serious infection develops, they should be closely monitored and STELARA should not be administered until infection resolves. Malignancies: Potential to increase the risk of malignancy. No studies in patients with a history of malignancy or in patients who develop malignancy while receiving STELARA. Monitor all patients, in particular those older than 60, patients with a medical history of prolonged immunosuppressant therapy or those with a history of PUVA treatment for non-melanoma skin cancer. Concomitant immunosuppressive therapy: Caution, including when changing immunosuppressive biologic agents. Hypersensitivity reactions: Serious hypersensitivity reactions (anaphylaxis and angioedema) reported, in some cases several days after treatment. If these occur, discontinue STELARA immediately and institute appropriate therapy. Immunotherapy: Not known whether STELARA affects allergy immunotherapy. Latex sensitivity: Needle cover contains natural rubber (latex), may cause allergic reactions.

SIDE EFFECTS: Serious side effects: Serious infections, malignancies. Very common: upper respiratory tract infection, nasopharyngitis. Common: hypersensitivity reactions (rash, urticaria), cellulitis, viral upper respiratory tract infection, depression, dizziness, headache, pharyngolaryngeal pain, nasal congestion, diarrhoea, pruritus, back pain, myalgia, arthralgia, fatigue, injection site erythema, antibodies to ustekinumab. Uncommon: herpes zoster infection, injection site reactions. Rare: serious hypersensitivity reactions (including anaphylaxis, angioedema), facial palsy Refer to SmPC for other side effects. FERTILITY: The effect of ustekinumab has not been evaluated. PREGNANCY: Should be avoided. Women of childbearing potential: Use effective contraception during treatment and for at least 15 weeks post-treatment. LACTATION: Limited data in humans. INTERACTIONS: In vitro, STELARA had no effect on CYP450 activities. Vaccinations: Live vaccines should not be given concurrently with STELARA, and should be witheld for at least 15 weeks after last dose of STELARA. STELARA can resume at least 2 weeks after such vaccinations. No data on secondary transmission of infection by live vaccines in patients receiving STELARA. Concomitant immunosuppressive therapy: The safety and effi cacy of STELARA in combination with other immunosuppressants, including biologics, or phototherapy have not been evaluated. LEGAL CATEGORY: POM PRESENTATIONS, PACK SIZES, PRODUCT LICENCE NUMBERS & BASIC NHS COSTS: STELARA 45mg: 1 x 0.5ml pre-fi lled syringe. EU/1/08/494/003. £2147 MARKETING AUTHORISATION HOLDER: JANSSEN-CILAG INTERNATIONAL NV, Turnhoutseweg 30, B-2340 Beerse, Belgium. FURTHER INFORMATION IS AVAILABLE FROM: Janssen-Cilag Ltd, 50 – 100 Holmers Farm Way, High Wycombe, Buckinghamshire, HP12 4EG UK. © Janssen-Cilag Ltd 2013Prescribing information last revised: 17/01/2013 PIVER: 170113

Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Janssen-Cilag Ltd on 01494 567447.

Reference: 1. Kimball A et al. Spring EADV 2012. P582.

…and the results are clear

5 years of data on sustained response...In Week 40 responders* in PHOENIX 1, a pivotal Phase III study:

- PASI 75 response rate at week 244 was over 79%1

- The results were consistent for both the 45mg and 90mg treatment groups1

Prescribing information and references available on reverse.

Indicated for the treatment of moderate to severe plaque psoriasis in adults who have failed to respond to, or have a contraindication to, or are intolerant to other systemic therapies including ciclosporin, methotrexate and PUVA.

*Week 40 responders comprised of patients who were randomised to Stelara® at baseline, were PASI 75

responders at both Weeks 28 and 40, and were re-randomised at Week 40 to continue 12-weekly

maintenance treatment with Stelara®.