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FINAL Psoriasis supplement index image

High cost drugs in psoriasis: how to optimise patient care and budgets

ILUMETRI®(tildrakizumab): prescribing information
Skilarence® (dimethyl fumarate): prescribing information

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Improving cost effectiveness through pathways of care for the management of psoriasis

Mohsin Ashraf, Lead Pharmacist, University Hospitals Derby and Burton NHS Foundation Trust

[The views and opinions of the author are not necessarily those of University Hospitals Derby and Burton NHS Foundation Trust]

Introduction

Psoriasis is an inflammatory skin condition affecting nearly 2% of the population in the UK.1 As this is a debilitating condition, numerous health technologies have been brought to market over the last decade. 

High-cost drugs (HCDs) for treating moderate-to-severe psoriasis can be categorised into systemic non-biologic and systemic biologic treatment options. Biologic treatments broadly operate by inhibiting one of the following cytokines: tumour necrosis factor (TNF), interleukin (IL)17, and IL-12/IL-23 to varying affinity or avidity (see Table 1). It is likely that the cytokine involved in an individual’s disease is one of these four cytokines, so if one agent fails a subsequent line of therapy is likely to work. 

With so many options within these modes of actions, most commissioners need to build an understanding of the differences within these classes to help formulate appropriate HCD pathways for psoriasis in adult patients. These pathways are often local and seek to give additional context in areas that NICE technology appraisals (TA) do not cover. This brings on several questions: how are such guidelines and pathways developed? What should be considered and who should be consulted? What criteria are used to differentiate treatment options?  

Table 1: Treatment options for psoriasis
ClassSystemyc non-biologic name

PDE-4 inhibitors

apremilast

FAEs

dimethyl fumarate

Class

Systemic biologic therapy name

Anti-TNFs

adalimumab, etanercept, certolizumab pegol, infliximab

IL-12/23 inhibitor

ustekinumab

IL-23 inhibitor

guselkumab, tildrakizumab, risankizumab

IL-17 inhibitors

ixekizumab, secukinumab

IL-17 receptor antagonist

brodalumab

FAE= fumaric acid ester; IL=interleukin; PDE=phosphodiesterase; TNF=tumour necrosis factor.

Pathways of care: clinical and cost effectiveness

NICE has the responsibility to appraise all new technologies; however, this causes significant challenges for local commissioners. New HCD for psoriasis are welcomed additions to the dermatologists’ armamentarium for treating this life-long condition. They provide scope for increased efficacy, less frequent dosing, improved adherence, and longer-term persistence of effect. However, resources are not limitless within the NHS, and difficult decisions must be made.  A new NICE TA mandates use, and therefore funding must be allocated by clinical commissioning groups (CCGs). The recent availability of biosimilar adalimumab has provided significant savings to the NHS. Most commissioners and secondary care providers horizon scan for new assets and try to plan for positive TAs. Budget constraints within the healthcare system bring forth the financial impact of any new TA high on the agenda for local health economies, so it is necessary to take cost variations into account. This is one of the reasons for the development of pathways for conditions such as psoriasis. 

Clinical pathways seek to document and set out a process of best practice in a focused patient group. Pathways consist of a distillation of expert opinions, and should be evidence based. Guidelines are needed when treatment options are many, there is no clear direction on practice, and resources are limited. Psoriasis is a perfect indication for a pathway along with other inflammatory conditions such as rheumatoid arthritis and irritable bowel disease. Without guidelines, costs may spiral while providing suboptimal value to the health economy. 

Any new pathway developed locally must have the engagement of all stakeholders. This includes primary care, secondary care, commissioning groups, and patient representatives. The effectiveness of any pathway, such as those developed for psoriasis, should be based on improved clinical outcomes or quality of life and care. However, from a commissioning point of view, additional benefits such as reduced variation in practice, standardisation of resource allocation, and clinical effectiveness in terms of cost and resource reduction are just as important. Naturally, there will be variation in opinions amongst clinicians and patient advocates, but it is important that treatment options are considered in the context of both clinical and cost effectiveness. For example, there are pathways that list treatment options in order of acquisition cost (e.g. West Essex).2 The populations served by each CCG will differ as well as the availability of expertise in secondary care settings. These are some potential barriers to agreeing a pathway. Each representative will have a different set of priorities; to overcome this a compromise must be made to allow patients to have access to the treatments they need, to allow clinicians to have enough freedom to enact their own judgements, and to allow enough oversight for CCGs to have the assurance of best value and clinical effectiveness. 

Sequential switching between systemic biologic treatments is one of the methods to enact cost savings while providing patients with increased treatment options. NICE clinical guideline 153 provides an evidence-based review of comparative biologic therapies in chronic plaque psoriasis.3 The British Association of Dermatologists guidelines for biologic therapy for psoriasis advises to seek advice from a clinician with expertise in biologic therapy when a patient’s psoriasis responds inadequately to a second or subsequent biologic agent.4 NICE estimates the cost of best supportive care to be £10,730 per year.5 The cost of systemic biological treatments will vary depending on the agents previously used. A third line systemic treatment option should cost less than the best supportive care, and should thus offer cost savings.  Patients with severe psoriasis and very severe psoriasis who have failed their second biological therapy may need repeated outpatient appointments, sometimes needing repeated day treatments and frequent hospital admissions. Biologic drugs have a yearly attrition rate of 15% resulting in patients having to switch to a different treatment for long-term control.6 As further evidence is now available, sequential switching is becoming the norm, whereas NICE only approves two systemic biologic treatment options. This goes to show how guidelines can enhance patient care, provide cost savings, and are more adaptable to current evidence.

An example of an advanced psoriasis pathway is from the Greater Manchester Medicines Management Group,7 and allows clinicians four treatment options and a further two with a multidisciplinary team input before resorting to an individual funding request. In addition, the use of non-biologic treatments is recommended at any stage of the pathway when their use is deemed preferable to biologics. This is an excellent example of understanding psoriasis as a condition with debilitating impact on patients, taking into account the various treatment options and balancing this with cost and clinical effectiveness. Close monitoring on implementation of such a pathway is essential, and can be done using regular audits or Blueteq (if available). 

Limiting biologic choice and options is common across England; however, a recent advisory statement by the Regional Medicines Optimisation Committee (RMOC) on sequential use of biologics may change this for the foreseeable future, not only for psoriasis but for all inflammatory conditions.

Finally, patient factors should be given more attention when prescribing. Patients should be given a range of options and be allowed to choose which is best for them, if they wish, as this will positively impact adherence. Routes and frequency of administration are very important factors for some patients, and this option is not routinely built into psoriasis pathways. 

Adjusting care to the COVID-19 pandemic

The COVID-19 pandemic has put pressure on existing pathways. During this unprecedented time, the NHS has quickly adjusted its operations to ensure patient and clinician safety. Many changes occurred in a short period of time, such as remote virtual clinics, reduced monitoring appointments, and moving phlebotomy into primary care where possible. Some of these changes have been assisted by pharma-funded services in addition to homecare, where trusts have chosen to adopt them. NICE guideline 169 has suggested monitoring can be modified from usual times,9 and Guy’s & St Thomas’ NHS foundation trust has developed a suggested guide on how to modify monitoring and follow ups for those patients on systemic biologic therapy.10 A greater discussion needs to take place on assessing and taking into account frequency of administration, safety profiles of medicines, monitoring frequency, patient outcomes, and adherence. Newer therapies may offer advantages in this respect compared to older agents. This should be taken into consideration alongside cost, supply chain robustness, and patient preference. Where possible, remote consultations are great for patients and clinicians alike, but a face-to-face assessment cannot be replaced by a remote one, for now. I believe we have had a glimpse of what the future may look like, but I would proceed with caution so to not compromise patient safety. 

Conclusion

The development of guidelines is complex and must take into consideration current evidence, resource impact analysis, and horizon scanning. Their development must be done with input from all stakeholders. The aim of any guideline must be to secure best value treatment for patients, while allowing clinicians the freedom to enact their judgement, and giving CCGs the confidence in compliance and cost effectiveness. At the moment, patient factors are not given enough precedence in guidelines, although there are some excellent examples of guidelines for psoriasis in England. Sequential switching between biologics has been limited to date, however the recent RMOC statement should bring about a change in this policy. 

References

  1. Parisi R et al. J Invest Dermatol 2013; 133 (2): 377–385.
  2. West Essex CCG. Pathway for Plaque Psoriasis. November 2019. Available at: https://westessexccg.nhs.uk/your-health/medicines-optimisation-and-pharmacy/high-cost-drug-policies-and-pro-formas/dermatology/psoriasis/192-pathway-for-plaque-psoriasis/file
  3. NICE. Psoriasis: Assessment and management. Clinical Guideline 153. NICE, 2012 (last updated 2017). Available at: www.nice.org.uk/cg153
  4. Smith C et al. Br J Dermatol 2017; 177: 628–636.
  5. NICE. Psoriasis guideline—appendices J–U. October 2012. Available at: www.nice.org.uk/guidance/cg153/evidence/appendices-ag-pdf-188351536
  6. NHS Fife. High cost drugs pathway for adults with psoriasis. October 2018. Available at: www.fifeadtc.scot.nhs.uk/media/27063/nhs-fife-high-cost-drugs-psoriasis-pathway-2018-v1-2.pdf
  7. Great Manchester Medicine Management Group. High cost drugs pathway for psoriasis in adults: outcomes and monitoring framework. January 2020. Available at: http://gmmmg.nhs.uk/docs/guidance/Psoriasis-pathway-outcome-monitor-final-2020-01.pdf
  8. Regional Medicine Optimisation Committee. Regional Medicine Optimisation Committee (RMOC) advisory statement—sequential use of biologic medicines. May 2020. Available at: www.sps.nhs.uk/articles/rmoc-advisory-statement-sequential-use-of-biologic-medicines
  9. NICE. COVID-19 rapid guideline: dermatological conditions treated with drugs affecting the immune response. NICE Guideline 169. NICE, 2020. Available at: www.nice.org.uk/ng169
  10. Guy’s and Thomas’ NHS Foundation Trust. Safe prescribing and monitoring protocol for systemic immunomodulatory therapies for immune-mediated inflammatory skin disease in the context of Coronavirus (COVID-19). March 2020. Available at: www.bad.org.uk/shared/get-file.ashx?itemtype=document&id=6656 

The development of local pathways of care for moderate-to-severe psoriasis

Dr Laura Savage, Consultant Dermatologist, Leeds Teaching Hospitals NHS Foundation Trust; Honorary Senior Lecturer, University of Leeds

Introduction

Psoriasis is a common, chronic, immune-mediated papulosquamous dermatosis with a highly variable morphology, distribution, severity, and course. It is estimated that at least 100 million individuals are affected worldwide, with the reported prevalence in countries ranging between 0.09% and 11.43%.1 In the UK, 1.2 million people are thought to have psoriasis,2 with frequent functional, psychological, and social morbidity and consequent reduced levels of employment and income.3 Psoriatic inflammation drives a broad range of comorbidities including arthritis, cardiovascular diseases, metabolic syndrome, inflammatory bowel disease, and depression. Patients with psoriatic disease, therefore, often necessitate substantial cumulative usage of both primary and secondary healthcare resources.4

One fundamental mission of the NHS is ensuring the efficient delivery of high-quality primary, secondary, and tertiary care across all specialties, including dermatology. However, with finite budgets and increasing demand for services, selecting interventions and treatments to prioritise can be difficult. Over the past 20 years, the management of many diseases, including psoriasis, has been revolutionised through the advent of targeted biologic therapies, providing highly efficacious options for treatment with a good safety profile. However, such drugs come at high costs and therefore must be subject to appraisal by NICE. While therapeutic expansion in response to deepened understanding of pathogenic mechanisms is beneficial to patients (see Figure 1 for the evolution of psoriasis therapies over time), increasing choice adds further cost pressure to already constrained budgets. Rationing of high-cost drugs to those in greatest need while utilising the most cost-effective treatment is therefore imperative to stop budgets from spiralling and provide optimum value to the health economy. This is one reason for the development of both national NICE guidelines and local care pathways for disease-specific areas such as psoriasis: to promote organised, evidence-based, and cost-effective patient care.

Ample guidance for treating psoriasis exists within a stepwise framework, and clear signposting for when a patient requires referral for specialist advice is available.3, 5–7 However, a lack of confidence in managing psoriasis compared with other conditions in primary care remains.8 The rapid expansion of approved novel immunomodulators has also led many non-sub specialised dermatologists to feel overwhelmed by choice and seeking further education regarding the positioning of novel biologic agents and oral small molecules within their therapeutic armamentarium. National and local care pathways are therefore not only beneficial to stratify access due to financial limitations, but can also be vital to guide clinicians to make evidence-based treatment decisions to optimise patient outcomes. 

Almirall Figure 1

IL=interleukin; MTX=methotrexate; PASI=Psoriasis Area and Severity Index; TNF=tumour necrosis factor.

Figure 1: The evolution of psoriasis therapy

Biologic treatments for psoriasis

When choosing a therapy for psoriasis, healthcare professionals should keep in mind the current understanding of the pathways involved and how biologic therapies influence them. Psoriasis is a T cell-mediated disease in which interleukin (IL)-12 and IL-23, released by activated dendritic cells, differentiate naïve T helper (Th) cells into Th1, Th17, and Th22 cells. These cells produce additional cytokines, including interferon (IFN)-γ, tumor necrosis factor (TNF), IL-17, and IL-22, which propagate the immune response and lead to keratinocyte hyperproliferation.9 Biologics act by altering T-cell activation, effector cytokines, or cytokine receptors. As shown in Figure 2, current NICE-appraised biologics for psoriasis comprise four TNF antagonists (etanercept, adalimumab, infliximab, certolizumab)[A] one anti-IL-12/23p40 monoclonal antibody (ustekinumab)[A] and two anti-IL-17A monoclonal antibodies (secukinumab and ixekizumab), [A] one IL-17 receptor antagonist (brodalumab)[A] and three anti-IL-23p19 monoclonal antibodies (guselkumab, risankizumab, tildrakizumab). [A] Table 1 summarises the characteristics of the five classes of biologics for psoriasis. 

[A] Summary of product characteristics for individual products can be found at www.medicines.org.uk/emc

Almirall Figure 2

Huppler A et al. Arthritis Res Ther 2012; 14 (4): 217
DC=dendritic cell; IFN=interferon; IL=interleukin; JAK=janus kinase; PDE4=phosphodiesterase-4; TNF=tumour necrosis factor.

Figure 2: Pathogenesis of psoriasis and biologic targets

Table 1: Biologics licensed for the treatment of psoriasis (please consult individual summary of product characteristics before prescribing)
TargetLicenced drug(s)Advantages Disadvantages 

TNFi

Adalimumab[A]

  • Dual licence (psoriasis and PsA); similar efficacy of ADA and SEC15
  • Good efficacy in nail and scalp disease (ADA and ETA)16,17
  • Shorter half-life than other biologics (if cessation required)
  • Cost: with the exception of CTZ, biosimilar versions of TNFi are cheaper than originator biologics within all classes
  • CTZ may be used during pregnancy and can be used during lactation18,19
  • Frequency of dosing/posology
  • Less effective on palmoplantar disease than other classes of biologics20,21
  • Highest rates of anti-drug antibody formation across all classes leading to secondary inefficacy22
  • Contraindicated in patients with cardiac failure, and active severe/opportunistic infections
  • Discontinue if lupus-like syndrome develops, caution/discontinue if demyelinating disease occurs (pre-existing or de-novo)
  • Higher rates of injection site reactions compared to other classes of biologics23

Certolizumab[A]

Etanercept[A]

Infliximab[A]

IL-12/23p40

Ustekinumab[A]

  • Available as 45 mg or 90 mg doses (at the same price)
  • Most infrequent dosing (12-weekly) compared to TNFi and IL-17i/RA
  • Dual licence (psoriasis and PsA)
  • Stringent weight-based dosing
  • High cost compared to biosimilar TNFi
  • Long half-life if discontinuation required
  • Less efficacious in PsA compared to ADA and SEC24

IL-23p19

Guselkumab[A]

  • Most infrequent dosing (8- or 12-weekly) compared to TNFi and IL-17i/RA
  • No specific contraindications above those for all biologic therapies
  • Minimal impact on efficacy if priorly treated with ADA or UST (GUS, RIS)25–28
  • Superior quality of life improvement compared to UST and TNFi (RIS, GUS) 25–28
  • No apparent loss of efficacy in patients with higher BMI compared to other classes 29–31
  • TIL available as 100 mg or 200 mg doses (at the same price)
  • Not licensed for PsA
  • Two injections per dose required for RIS
  • High cost compared to biosimilar TNFi
  • Long half-life if discontinuation required

Risankizumab[A]

Tildrakizumab[A]

IL-17A

Ixekizumab[A]

  • Superior efficacy against UST in head-to-head trials over 52 weeks 32–34
  • High efficacy in nail and scalp psoriasis35,36
  • Superior quality of life improvement compared to UST and TNFi 32–34
  • Good efficacy in genital psoriasis (IXE)37 and palmoplantar psoriasis (SEC)38
  • Dual licence (psoriasis and PsA), with superior efficacy demonstrated against ADA (IXE)39
  • Contraindicated in patients with clinically important active infections (e.g. active tubercolosis)
  • Not recommended in patients with IBD
  • Two injections per dose required for SEC
  • Higher rates of injection site reactions compared to other classes of biologics40,41
  • High cost compared to biosimilar TNFi
  • No flexibility with dosing

Secukinumab[A]

IL-17R

Brodalumab[A]

  • Superior efficacy against UST in head-to-head trials42,43
  • High efficacy in nail and scalp psoriasis44  
  • Not licensed for PsA
  • High cost compared to biosimilar TNFi
  • Contraindicated in patients active Crohn’s disease and important active infections (e.g. active tubercolosis)
  • Not recommended/discontinue in patients with IBD
  • No flexibility with dosing

ADA=adalimumab; BMI=body mass index; CTZ=certolizumab; ETA=etanercept; GUS=guselkumab; IBD=inflammatory bowel diesease; IL=interleukin; IXE=ixekizumab; PsA=psoriatic arthritis; RIS=risankizumab; SEC=secukinumab; TIL=tildrakizumab; TNFi=tumour necrosis factor inhibitor; UST=ustekinumab.

[A]Summary of product characteristics for individual products can be found at www.medicines.org.uk/emc

Best practice in developing pathways of care

Engagement of all stakeholders is paramount when developing a new local care pathway. This includes primary care, secondary care, patient representatives, managers, and commissioners. The effectiveness of any pathway should be based on both improved clinical and quality of life outcomes and the delivery of high-quality care. Pathways are advocated to reduce variation in practice, to improve clinical effectiveness, and provide value for money. The temptation is therefore to constrain access to a limited number of biologic agents with strict sequencing, but there needs to be a fine balance between providing guidance to clinicians and potentially restricting patients’ access to the right therapy. A recent Regional Medicines Optimisation Committee (RMOC) advisory statement on sequential use of biologics stated that limiting biologic choice and options would go against the provisions of the NHS constitution, which pledges that ‘patients have the right to drugs and treatments that have been recommended by NICE subject to being clinically appropriate, and have the right to expect local decisions on the funding of drugs and treatments to be made rationally and following the proper consideration of evidence’.10 No single treatment option is effective or appropriate for all patients with psoriasis, largely due to the fact that the pathophysiology of psoriasis is multifaceted and involves a complex interaction between genetic, environmental, and immunological factors.9

A number of landmark studies using novel approaches such as genome-wide association studies and bioinformatics tools for transcriptomics analysis have identified numerous single nucleotide polymorphisms, genes, and altered signalling pathways, which have provided insights into the relationship between specific genetic predisposition and immunopathological mechanisms driving psoriasis. Despite this knowledge, some patients remain refractory to one biologic treatment and not others, driving the urgent need for precision medicine in psoriasis. Personalised regimens would lead to a myriad of benefits including tighter disease control, the development of fewer co-morbidities, less drug wastage due to trial and error, and enhanced patient satisfaction. 

While clinicians eagerly await the feasibility to deliver precision medicine, dermatologists can offer some of its benefits by adopting a stratified approach to the selection of biologic therapy for each individual by considering patient- and disease-related factors in addition to high-quality clinical trial data (including phase III head-to-head comparator trials) and real-world evidence. Evidence from clinical trials provides pertinent short- and long-term information regarding the safety and efficacy of biologic agents for psoriasis in a controlled population, and clinicians should consider how disease presentation, distribution, and severity, alongside comorbid conditions, response to previous therapy, age, and body mass index (BMI) can influence treatment outcomes. Adherence may be improved by considering the patients’ preferences (e.g. posology) and lifestyle, and conception plans must be discussed in women of child-bearing age. Only by allowing dermatologists some flexibility to consider all of these factors within local pathways of care can they attempt to ‘get it right first time’ rather than subscribing to the paradigm that ‘one size fits all’. 

Selecting the right biologic the first time has an impact on drug expenditure aside from the benefits to a patient’s physical and mental wellbeing. Switching a biologic is expensive and time consuming for patient and clinician. Drug loading can increase the cost of a biologic by 20–25% in the first year,11 and indirect costs such as reduced or lost work productivity for the patient must be appreciated.3,12 While limiting the number of biologics a patient may access may seem to be a way of reducing the cost associated with switching, this is a naïve position given the increase in outpatient appointments, day case attendances, and hospital admissions that result from patients inadequately controlled and in flare. The cost of switching can be minimised by increasing access, rather than restricting it, allowing dermatologists to position the most efficacious therapies with the highest persistence of response earlier in the therapeutic pathway. On the whole, biologic agents have a yearly attrition rate of 15%,13 and therefore long-term clinical trials and real-world outcome studies, especially around persistence of response, are of greatest importance when reviewing treatment efficacy and comparing cost-effectiveness. Clinicians should seek to obtain locally-negotiated drug acquisition costs to help make such assessments, which can sometimes vary by several thousand pounds within each class. Budgetary control can also be maintained to some extent by limiting access to therapy to only those in greatest need (e.g. PASI and DLQI scores ≥10), by undertaking regular audits or Blueteq (where available), by requesting that clinicians consider biosimilar adalimumab first-line if patients and their clinicians consider it to be one of a range of potential suitable treatments (on the basis of least cost), and stipulating that more refractory patients (such as those who have failed on two biologic therapies) are reviewed by a dermatologist with a special interest in complex psoriasis, in accordance with the guidelines from the British Association of Dermatologists (BAD).6

COVID-19: changes to patients’ care

The COVID-19 pandemic has provided new challenges and alterations to pathways to ensure patients’ safety. The pace of these changes was unprecedented and initially based on limited evidence. Patients prescribed biologics were contacted and helped to determine their personal risk from COVID-19, and advised to shield if they were using more than one form of immunosuppression, were aged over 70, or had comorbidities. Guidance from BAD was instrumental in providing a uniform approach across the UK, and provided clinicians with much needed reassurance.14 Even through the recovery phase, consultations continue to be held remotely, either by telephone or video, and monitoring in the community or in primary care is performed with reduced frequency where possible. For a time, the prescribing of new systemic immunosuppression was halted, with patients encouraged to optimise their topical therapy or use non-immunosuppressive treatments such as acitretin, if appropriate. Many patients chose to discontinue their treatment due to fears of increased susceptibility to, or worse outcomes from, COVID-19. Unsurprisingly, increasingly volumes of patients are now requiring review, initiation, or a change in immunosuppressive therapy, and departments are starting to increase their capacity for face-to-face reviews, with strict social distancing policies in place. While there is no substitute for physically seeing and feeling a patient’s skin, for patients well controlled on biologic therapy, the pandemic has provided an opportunity to evaluate both the frequency and functionality of remote review, with many patients preferring the convenience of a telephone or video call. The focus at the present time is on managing clinic backlogs and prioritising those in flare, but time should be invested in due course into evaluating the beneficial aspects of remote working for patients with psoriasis and incorporating them into local pathways of care. 

Conclusion

The current goal in psoriasis is to optimise responses to available biologic therapies through stratification according to disease severity, distribution, comorbidities, prior response to other treatments, BMI, age, and other patient factors that influence responses to therapy. These needs to be coupled with clinical judgment of individual patient factors, such as perceived effect of disease on quality of life, the patient’s environment and lifestyle, and the potential adverse effects associated with given therapies. Regular assessments of therapy are important, either face to face or remotely, and therapies should be switched if control is inadequate. Local pathways of care should be outcomes-focused, and advocated to promote the implementation of key principles of good care and reduce non-evidence based variations in practice. In accordance with the RMOC, they should permit sequential switching yet provide clinicians with guidance on biologic selection to facilitate positioning of each drug for each individual. Pathways also provide the opportunity to identify areas of need and develop services that are accessible and acceptable to all psoriasis patients, and should be reviewed in the coming months to embrace the positive changes that the COVID-19 pandemic has imposed in terms of virtual consultations.

References

  1. World Health Organisation. Global report on psoriasis. WHO, 2016. Available at: apps.who.int/iris/bitstream/handle/10665/204417/9789241565189_eng.pdf?sequence=1&isAllowed=y
  2. Moon H et al. Dermatol Ther (Heideld) 2013; 23: 117–130.
  3. NICE. Psoriasis: assessment and management. Clinical Guideline 153. NICE, 2012 (updated September 2017). Available at: www.nice.org.uk/guidance/cg153
  4. Kimball A et al. J Eur Acad Dermatol Venereol 2011; 25: 157–63.
  5. Scottish Intercollegiate Guidelines Network. Diagnosis and management of psoriasis and psoriatic arthritis in adults. Edinburgh: SIGN; October 2010. (SIGN publication no. 121). Available at: www.sign.ac.uk/assets/sign121.pdf
  6. Smith C et al. Br J Dermatol 2020; doi:10.1111/bjd.19039.
  7. Bhatti K et al. Psoriasis—primary care treatment pathway. PCDS, 2017. Available at: www.pcds.org.uk/ee/images/uploads/general/Psoriasis_Treatment_2019-web.pdf
  8. Nelson P et al. BMC Fam Pract 2013; 14: 158.
  9. Lowes M et al. Ann Rev Immunol 2014; 32: 227–55.
  10. Specialist Pharmacy Service. Updated RMOC Advisory Statement on the Sequential Use of Biologic Medicines. January 2020. Available at: www.sps.nhs.uk/articles/rmoc-advisory-statement-sequential-use-of-biologic-medicines/
  11. Guerriero F et al. Clinicoecon Outcomes Res 2017; 9: 741–748.
  12. Armstrong A et al. PLoS One 2012; 7: e52935
  13. NHS Fife. High cost drugs pathway for adults with psoriasis. October 2018. Available at: www.fifeadtc.scot.nhs.uk/media/27063/nhs-fife-high-cost-drugs-psoriasis-pathway-2018-v1-2.pdf
  14. British Association of Dermatologists. Dermatology Advice Regarding Medication Acting on the Immune System: Adults, Paediatrics and Young People. April 2020. Available at: www.bad.org.uk/shared/get-file.ashx?itemtype=document&id=6674
  15. McInnes I et al. Lancet 2020; 395: 1496–1505.
  16. Elewski B et al. J Am Acad Dermatol 2018; 78 (1): 90–99.e1.
  17. Bagel J et al. J Am Acad Dermatol 2012; 67 (1): 86–92.
  18. Mariett X et al. Ann Rheum Dis 2018; 77 (2): 228–233.
  19. Clowse M et al. Ann Rheum Dis 2017; 76: 1890–1896.
  20. Leonardi C et al. Arch Dermatol 2011; 147 (4): 429–436.
  21. Menter A et al.  J Eur Acad Dermatol Venereol 2017; 31 (10): 1686–1692.
  22. Carrascosa J et al. J Eur Acad Dermatol Venereol 2014; 28: 1424–1430.
  23. Specialist Pharmacy Service. Update on development of biosimilar versions of adalimumab with particular focus on excipients and injection site reactions. December 2018. Available at: www.sps.nhs.uk/wp-content/uploads/2019/01/Adalimumab-Biosimilar-Comparison_V8.pdf
  24. Yiu Z et al.  Br J Dermatol 2020; 183: 294–302.
  25. Blauvelt A et al. J Am Acad Dermatol 2017; 76 (3): 405–417.
  26. Reich K et al. J Am Acad Dermatol 2017; 76 (3): 418–431.
  27. Langley R et al. Br J Dermatol 2018;178 (1): 114–123.
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  29. Armstrong A et al. Poster ppresented at the World Congress of Dermatology (WCD); late-breaking abstract 524.
  30. Gordon K et al. Br J Dermatol 2018; 178 (1): 132–139.
  31. Leonardi C et al. Poster 5248, presented at the World Congress of Dermatology (WCD).
  32. Thaçi D et al. J Am Acad Dermatol 2015; 73: 400–409.
  33. Bagel J et al.  J Eur Acad Dermatol Venereol doi:10.1111/jdv.16558.
  34. Reich K et al. Br J Dermatol 2017; 177 (4): 1014–1023.
  35. Bagel J et al. J Am Acad Dermatol 2017; 77: 667–674.
  36. Reich K et al. Br J Dermatol 2019; 181 (5): 954–966.
  37. Ryan C et al. Br J Dermatol 2018; 179 (4): 844–852.  
  38. Gottlieb A et al. Br J Dermatol 2020; 182 (4): 889–899.
  39. Mease P et al.Ann Rheum Dis 2020; 79: 123–131.
  40. Mahil S et al. Br J Dermatol 2020 Accepted Author Manuscript. doi:10.1111/bjd.19325
  41. Blauvelt A et al. Br J Dermatol 2020;182 (6): 1348–1358.
  42. Puig L et al. J Am Acad Dermatol 2020;82 (2): 352–359.
  43. Strober B et al. J Am Acad Dermatol 2015; 72 (5) Supplement 1: AB224
  44. Elewski B et al. J Dermatolog Treat 2020; 1–5. Online ahead of print.   

UK-NOP-2000055
Date of preparation: October 2020