Clinical Protocol Atopic Dermatitis Dupilumab Treatment Pathway - NHS Lambeth CCG
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Clinical Protocol
Atopic Dermatitis
Dupilumab Treatment Pathway
Guideline Summary
This clinical guideline outlines the dupilumab treatment pathway for adult patients with atopic
dermatitis
South East London Integrated Medicines Optimisation Committee. A partnership between NHS organisations in South East London: South East
London Clinical Commissioning Group (covering the boroughs of Bexley, Bromley, Greenwich, Lambeth, Lewisham and Southwark) and GSTFT/KCH
/SLaM / Oxleas NHS Foundation Trusts and Lewisham & Greenwich NHS Trust
Approved: June 2021 Review Date: June 2022
Not to be used for commercial or marketing purposes. Strictly for use within the NHS. Page 1 of 18Document Detail
Document Type Clinical Guideline
Document name Atopic Dermatitis Dupilumab Treatment Pathway
Document location Intranet of Individual Trusts
Version Draft Version 1.3
Effective from June 2021
Review due date June 2022
Owner South East London Dermatology Pathway Group
Author South East London Dermatology Pathway Group:
Guy’s & St Thomas’ NHS Foundation Trust
Specialist Clinical Pharmacist Dermatology & Allergy
Specialist Clinical Pharmacist Dermatology & Allergy
Professor of Dermatology and Therapeutics, Consultant Dermatologist
Consultant Dermatologist
Consultant Nurse Dermatology
King’s College London NHS Foundation Trust
Consultant Dermatologist
Specialist Pharmacist – Dermatology
Lewisham and Greenwich NHS Trust
Specialist Pharmacist
Consultant Dermatologist
Clinical Commissioning Groups
Senior Prescribing Advisor, NHS SEL CCG (Bromley)
Senior Pharmacist Commissioning, NHS SEL CCG (Southwark)
Approved by, date SEL Integrated Medicines Optimisation Committee: 27th May 2021
SEL Medicines Optimisation sub-Committee: 10th June 2021
Superseded Nil
documents
Related Documents Technology appraisal guidance [TA534] National Institute for Health and Care
Excellence - Dupilumab for treating moderate to severe atopic dermatitis.
Published date: 01 August 2018 https://www.nice.org.uk/guidance/ta534
Summary of Product Characteristics Dupixent® 300mg solution for injection in
pre-filled syringe. Last updated 06 Jan 2021
https://www.medicines.org.uk/emc/product/8553
Keywords Atopic dermatitis, dupilumab
Change History
Date Change details, since approval Approved by
Review History
Date Review details Approved by
South East London Integrated Medicines Optimisation Committee. A partnership between NHS organisations in South East London: South East
London Clinical Commissioning Group (covering the boroughs of Bexley, Bromley, Greenwich, Lambeth, Lewisham and Southwark) and GSTFT/KCH
/SLaM / Oxleas NHS Foundation Trusts and Lewisham & Greenwich NHS Trust
Approved: June 2021 Review Date: June 2022
Not to be used for commercial or marketing purposes. Strictly for use within the NHS. Page 2 of 18Contents
1. Scope
2. Rationale
3. Principles
4. Eligibility criteria for dupilumab in line with NICE guidance
5. Definitions
6. Recommended disease severity assessments, before and during therapy
7. Pre-dupilumab therapy – key considerations
8. Communication to GP
9. Recruitment into clinical trials
10. Use of dupilumab and vaccinations
11. Dupilumab therapy and infection risk recommendations
12. Biologic therapy and malignancy risk recommendations
13. Dupilumab with co-morbid asthma
14. Use of biologic therapy in women planning pregnancy or who are pregnant
15. Use of dupilumab therapy in the perioperative period for surgery
16. Use of dupilumab therapy in patients with chronic viral infections
17. Reported side effects
18. Dupilumab therapy and ocular side effects
19. Dupilumab therapy and musculoskeletal side effects
20. Method of medication supply
21. Monitoring adherence with this pathway
22. Supporting documents
Practical Points for Primary Care
Appendices:
Appendix 1 - Suggested pre-dupilumab screening and monitoring schedule
Appendix 2 – Half Life of Common Treatments
Appendix 3 – Dupilumab initiation letter template to GP
Appendix 4 – Service Quality Standards
South East London Integrated Medicines Optimisation Committee. A partnership between NHS organisations in South East London: South East
London Clinical Commissioning Group (covering the boroughs of Bexley, Bromley, Greenwich, Lambeth, Lewisham and Southwark) and GSTFT/KCH
/SLaM / Oxleas NHS Foundation Trusts and Lewisham & Greenwich NHS Trust
Approved: June 2021 Review Date: June 2022
Not to be used for commercial or marketing purposes. Strictly for use within the NHS. Page 3 of 181. Scope
This treatment pathway applies to adult patients with a diagnosis of atopic dermatitis who are
eligible for treatment with dupilumab in secondary or tertiary care, in accordance with NICE
guidance.
2. Rationale
This treatment pathway provides an evidence-based approach for the treatment of atopic
dermatitis with dupilumab that maximises cost-effectiveness and clinical outcomes, for use by all
healthcare professionals involved in patient care.
3. Principles
This treatment pathway is based on current national guidance (NICE technology appraisal, TA534),
source evidence of efficacy, safety and cost effectiveness (Dupixent® Summary of Product
Characteristics) and locally approved guidance on the use of dupilumab in adults with atopic
dermatitis which draws on expert opinion from the Medical Dermatology multi-disciplinary
teams. This pathway is subject to frequent change as guidance is updated, new biologic agents to
treat atopic dermatitis emerge and costs change. This guideline will therefore be under active
review in light of the above. This document is not designed to replace the above guidance; URLs
are embedded within the document where relevant. This pathway assumes that prescribers
cross-reference the Summary of Product Characteristic (SPC) to inform clinical decision making
for individual patients (www.medicines.org.uk/emc). In order to ensure effective service
provision in line with the pathway the suggested service quality standards are outlined in
appendix 4.
4. Eligibility criteria for dupilumab in line with NICE guidance
Dupilumab is recommended as an option for treating moderate to severe atopic dermatitis in adults
only if the disease has not responded to at least 1 other systemic therapy, such as, ciclosporin,
methotrexate, azathioprine and mycophenolate mofetil, or if these treatments are contraindicated or
not tolerated
All patients who fulfil the above eligibility criteria for dupilumab should be offered dupilumab in line
with NICE guidance. The recommended dose, given by subcutaneous injection, is initially 600 mg (2 ×
300mg injections), followed by 300 mg given every other week. The decision to proceed with
treatment must be made in collaboration with the patient and include: confirmation that the patient
has atopic dermatitis and has had an adequate trial of at least one systemic therapy, and a detailed
discussion around the advantages and disadvantages of using a newer treatment (with less patient
exposure) versus other systemic therapies (such as azathioprine, mycophenolate mofetil,
methotrexate or ciclosporin). All patients receiving dupilumab should be under the care of a
consultant in a specialist dermatology service.
Other systemic therapies that could be used prior to dupilumab as per the NICE guidance, should be
trialled for at least three months at a clinically appropriate, therapeutic dose as follows:
Licensed treatments:
• Ciclosporin (licensed for short-term use only, up to 1 year maximum): 2.5mg/kg/day in divided
doses increased to 5mg/kg/day, depending on tolerability and response
South East London Integrated Medicines Optimisation Committee.
A partnership between NHS organisations in South East London: South East London Clinical Commissioning Group (covering the boroughs of Bexley,
Bromley, Greenwich, Lambeth, Lewisham and Southwark) and GSTFT/KCH /SLaM/ & Oxleas NHS Foundation Trusts/Lewisham & Greenwich NHS Trust
Approved: June 2021 Review Date: June 2022
Not to be used for commercial or marketing purposes. Strictly for use within the NHS. Page 4 of 18Unlicensed treatments:
• Methotrexate: incremental dosing from an initial dose of 2.5-15mg once a week to a maximum
dose of 25mg once a week, depending on tolerability and response
• Azathioprine: 1-3mg/kg/day, depending on thiopurine methyltransferase (TPMT) range,
tolerability and response
• Mycophenolate mofetil: 1g/day in divided doses increased to a maximum of 3g/day depending
on tolerability and response
Patients should be counselled prior to the initiation of the above medications, that they are being
prescribed outside of the terms of their license (‘off label’), and the rationale for prescribing should
be explained by the clinician.
Dupilumab should be stopped at 16 weeks of treatment if the atopic dermatitis has not responded
adequately as defined by NICE (see Section 5 for the definition of an adequate response as outlined
in the NICE Technology Appraisal)
5. Definitions
Moderate to severe disease – disease that cannot be controlled with topical therapy; has a
significant impact on physical, psychological or social wellbeing; and is either extensive, or
localised but associated with significant functional impairment and/or high levels of distress (for
example severe hand and foot eczema, or head and neck eczema).
Adequate response – at least a 50% reduction in the Eczema Area and Severity Index score
(EASI 50) and at least a 4-point reduction in the Dermatology Life Quality Index (DLQI) at 16 weeks
from when treatment started, as outlined by the NICE technology Appraisal.
Inadequate response – Failure to achieve the above.
6. Recommended disease severity assessments, before and during therapy
6.1 Assessment of disease severity
6.1.1 Physicians global assessment (PGA) classified as clear, nearly clear, mild, moderate,
severe
6.1.2 Eczema Assessment and Severity Index (EASI)
6.1.3 Dermatology Life Quality Index (DLQI)
6.1.4 Patient Oriented Eczema Measure (POEM)
7. Pre-dupilumab therapy – key considerations
7.1 Strategies for maximising the use of non-biological systemic treatments prior to biologic
therapy
If only a partial response is observed, ensure the dose of the systemic treatment is appropriately
optimised.
• Allow an 8-12 week interval following a dose change before assessment of response.
• If established on oral methotrexate or previously tolerated treatment with oral
methotrexate, consider a switch to subcutaneous methotrexate where clinically appropriate
South East London Integrated Medicines Optimisation Committee.
A partnership between NHS organisations in South East London: South East London Clinical Commissioning Group (covering the boroughs of Bexley,
Bromley, Greenwich, Lambeth, Lewisham and Southwark) and GSTFT/KCH /SLaM/ & Oxleas NHS Foundation Trusts/Lewisham & Greenwich NHS Trust
Approved: June 2021 Review Date: June 2022
Not to be used for commercial or marketing purposes. Strictly for use within the NHS. Page 5 of 18(e.g. gastrointestinal adverse effects with oral methotrexate, poor compliance or concerns
regarding absorption of oral formulation).
7.2 Provide high quality information to patient
The British Association of Dermatologists have produced a patient information leaflet on
dupilumab.
7.3 Complete recommended pre-biologic assessments
Refer to local and national guidance for full list of assessments needed pre-biologic therapy with
dupilumab. See Appendix 1 for suggested schedule for screening and monitoring.
7.4 Transitioning from other systemic treatment
If a patient is on a systemic treatment, consider if a washout period is required before commencing
dupilumab. This, however, needs to be balanced against the case-by-case risk of potential flare in
severity when the patient is off systemic therapy. See Appendix 2 for the half-lives of the common
systemic treatments.
8. Communication to GP
See Appendix 3 for dupilumab initiation GP letter template, which is recommended for use by the
specialist dermatology team to highlight key information regarding the use of dupilumab to the patients
GP.
9. Recruitment into clinical trials
When considering starting a patient on dupilumab, where applicable they should be invited to
participate in clinical research being undertaken within the dermatology department
10. Use of dupilumab and vaccinations
• Vaccination requirements should be reviewed and brought up to date prior to initiation of
biologic therapy with reference to Department of Health Guidance
• In general, biologic therapy can be started 4 weeks after administration of a live or live
attenuated vaccine. Stop dupilumab therapy for at least 12 months before giving live
vaccines, unless otherwise directed by a specialist (expert opinion suggests that 12 months
may not be necessary for all biologics). Refer to the SPC and the Department of Health
Green Book (Immunisation against infectious disease, Chapter 6) for further information.
• Inactivated vaccines are safe to administer concurrently with a biologic therapy; however,
where possible, inactivated vaccines should be administered 2 weeks before starting
therapy to ensure optimal immune responses.
• Patients should be advised to receive the pneumococcal polysaccharide vaccine (PPV),
annual ‘inactivated’ influenza vaccine and COVID-19 vaccine while on biologic therapy. The
GP should be asked to ensure the patient is flagged as being on immunosuppression and
requiring vaccination according to Department of Health Guidance.
South East London Integrated Medicines Optimisation Committee.
A partnership between NHS organisations in South East London: South East London Clinical Commissioning Group (covering the boroughs of Bexley,
Bromley, Greenwich, Lambeth, Lewisham and Southwark) and GSTFT/KCH /SLaM/ & Oxleas NHS Foundation Trusts/Lewisham & Greenwich NHS Trust
Approved: June 2021 Review Date: June 2022
Not to be used for commercial or marketing purposes. Strictly for use within the NHS. Page 6 of 18Refer to BAD immunisation document for further information.
11. Dupilumab therapy and infection risk recommendations
• Patients on biologic interventions should be monitored for signs and symptoms of infection
throughout treatment.
• Patients with a history of recurrent Herpes simplex or Varicella zoster should be discussed
with a virologist with respect to long-term suppressive therapy prior to commencement of
dupilumab.
• Check travel history prior to initiation of dupilumab therapy and enquire about prolonged
travel in areas endemic for parasitic infections, particularly helminths. Investigate as
warranted by history, e.g. strongyloides serology, schistosomiasis serology and stool sample
for ‘ova, cysts & parasites’. If concern, discuss risk assessment on a case-by-case basis with
an infectious diseases specialist and, if indicated, treat prior to initiation of dupilumab
therapy. Note that eosinophilia may not be a good marker for helminth infection in this
setting.
• If patients become infected with helminth while receiving treatment with dupilumab and do
not respond to anti-helminth treatment, treatment with dupilumab should be discontinued
until infection resolves, and the patient should be discussed with an infectious diseases
specialist.
12. Biologic therapy and malignancy risk recommendations
• All patients should be fully assessed prior to, and during treatment with biologic therapy
with respect to their past or current history of malignancy and/or any future risk of
malignancy; the risks and benefits of biologic therapy should be considered in this context.
• All patients should be encouraged to participate in national cancer screening programmes
appropriate for their age and gender.
• Biologic therapy should, whenever possible, be avoided in patients with a current or recent
past history of malignancy unless the malignancy has been diagnosed and treated more
than 5 years previously and/or where the likelihood of cure is high (this includes adequately
treated non-melanoma skin cancer).
• Patients who have a more recent history of malignancy should be discussed on a case-by-
case basis within the specialist eczema service, and with the relevant oncologist, to consider
(unknown) risks of dupilumab in the context of alternative available treatments.
• Consider gynaecological review for patients with a history of cervical dysplasia.
• Regular comprehensive dermatological assessment for skin cancer is recommended before
and at regular intervals during therapy, especially in those patients at increased risk of skin
cancer at baseline.
13. Dupilumab with co-morbid asthma
South East London Integrated Medicines Optimisation Committee.
A partnership between NHS organisations in South East London: South East London Clinical Commissioning Group (covering the boroughs of Bexley,
Bromley, Greenwich, Lambeth, Lewisham and Southwark) and GSTFT/KCH /SLaM/ & Oxleas NHS Foundation Trusts/Lewisham & Greenwich NHS Trust
Approved: June 2021 Review Date: June 2022
Not to be used for commercial or marketing purposes. Strictly for use within the NHS. Page 7 of 18• Dupilumab has proven safety and efficacy in asthma and is approved for the management of
severe asthma with type 2 inflammation by both the FDA (2018) and EMA (2019). It is
expected to undergo NICE review for use in severe asthma.
• Consider informing the patient’s GP and specialist respiratory team for review when a
patient with severe or unstable co-morbid asthma is commenced on dupilumab.
Hypereosinophilia was identified in a small number of cases in the phase 3 asthma trials of
dupilumab.
• A fatal asthma exacerbation occurred in a patient following cessation of dupilumab
treatment in the phase 3 atopic dermatitis programme. This was due to the patient stopping
their regular maintenance inhaled corticosteroid having improved on dupilumab.
For all patients with co-morbid asthma, they should be made aware that their asthma may
become more severe if dupilumab is discontinued. For patients with co-morbid severe or
unstable asthma, the asthma service should be informed at the time of discontinuation of
dupilumab to arrange additional monitoring within the asthma service.
14. Use of biologic therapy in women planning pregnancy or who are pregnant
• Advise women of childbearing potential, who are starting dupilumab for atopic dermatitis,
to use effective contraception and to discuss conception plans with the consultant
supervising their care. There are no known interactions between biologic therapies and
contraceptive methods
• For women planning conception or who are pregnant, provide information about what is
known about the effects of dupilumab, including the following:
o there is very limited data on the use of dupilumab in pregnant women, which is limited
to case reports and a small number of pregnancies in phase 2/3 trials for atopic
dermatitis and asthma.
o the available data is too limited and inadequately controlled to comment on the safety
of dupilumab in pregnancy.
o that maternal IgG, and therefore dupilumab, is actively transferred to the developing
fetus during the second and third trimester and that the impact of this on neonatal
development and risk of infection has not been adequately studied.
o the SPC states that ‘animal studies do not indicate direct or indirect harmful effects with
respect to reproductive toxicity. Dupixent® (dupilumab) should be used during
pregnancy only if the potential benefit justifies the potential risk to the fetus’.
o if there is a decision to stop dupilumab, the washout period should be considered 12
weeks.
o that live vaccines must be avoided for the first 6 months of life of infants born to
mothers taking biologic therapy beyond 16 weeks’ gestation.
o relevant patient information resources (SPC).
• Discuss the risks and benefits of using biologic therapy in women who are planning
conception or who are pregnant. Offer advice on a case‐by‐case basis by taking into account
the woman's views and:
o the available evidence (see above)
South East London Integrated Medicines Optimisation Committee.
A partnership between NHS organisations in South East London: South East London Clinical Commissioning Group (covering the boroughs of Bexley,
Bromley, Greenwich, Lambeth, Lewisham and Southwark) and GSTFT/KCH /SLaM/ & Oxleas NHS Foundation Trusts/Lewisham & Greenwich NHS Trust
Approved: June 2021 Review Date: June 2022
Not to be used for commercial or marketing purposes. Strictly for use within the NHS. Page 8 of 18o her current disease status
o the course of atopic dermatitis and the fetal outcome during any prior pregnancies
o the risk of severe or unstable atopic dermatitis without biologic therapy
o the importance of controlling severe or unstable atopic dermatitis to maintain maternal
health.
o her physical, psychological and social functioning without dupilumab therapy
o the options for alternative treatment strategies in the event of disease flare
• If the decision to use dupilumab during conception or pregnancy has been made:
o consider stopping biologic therapy in the second/third trimester (e.g. by week 28) to
minimize fetal exposure and limit potential risk to neonate, taking into account
individual biologics’ pharmacokinetics and transfer across the placenta.
o consider using either ciclosporin or prednisolone as first-line options when it is
necessary to start a systemic therapy during the second or third trimester
o that live vaccines must be avoided for the first 6 months of life of infants born to
mothers taking biologic therapy beyond 16 weeks’ gestation
• Ensure consultation and information sharing across specialities, including with an
obstetrician who has expertise in caring for pregnant women with medical problems.
• Collect pregnancy outcome data for safety registries, for example the UK Teratology
Information Service (UKTIS; www.uktis.org)
• Breast-feeding: Consider continuing or restarting dupilumab in women wishing to
breastfeed. Explain the benefits of breastfeeding and that the small amounts of biologic
therapy present in breast milk are unlikely to be absorbed systemically by the infant.
• Men: There is limited data regarding the use dupilumab by men around the time of
conception. This is limited to a small number of partner pregnancies of male study patients
in phase 2/3 trials for atopic dermatitis and inadequate to comment on the absolute safety
of dupilumab in men that plan to conceive on treatment. IL-4 and Il-13, the targets of
dupilumab, are not known to be involved in spermatogenesis. If there is a decision to stop
dupilumab, the washout period should be considered 12 weeks.
15. Use of dupilumab therapy in the perioperative period for surgery
• Although there is no evidence regarding the safe use of dupilumab peri-operatively, patients
are advised to omit the dose of dupilumab 2 weeks prior to major surgery. Therapy can be
restarted post operatively if wound healing is satisfactory and there is no evidence of infection.
• If a patient on dupilumab undergoes emergency major surgery, stop the dupilumab and do not
restart until postoperative wound healing is satisfactory and there is no evidence of infection.
16. Use of dupilumab therapy in patients with chronic viral infections
There is insufficient evidence to recommend treatment with biologic therapy in patients with
known chronic viral infections especially blood borne viruses, such as HIV and hepatitis B or C.
Clinicians should seek specialist advice on a case-by-case basis.
South East London Integrated Medicines Optimisation Committee.
A partnership between NHS organisations in South East London: South East London Clinical Commissioning Group (covering the boroughs of Bexley,
Bromley, Greenwich, Lambeth, Lewisham and Southwark) and GSTFT/KCH /SLaM/ & Oxleas NHS Foundation Trusts/Lewisham & Greenwich NHS Trust
Approved: June 2021 Review Date: June 2022
Not to be used for commercial or marketing purposes. Strictly for use within the NHS. Page 9 of 1817. Reported side effects
• Adverse reactions observed in atopic dermatitis clinical trials and/or post-marketing setting (*)
as reported in Dupixent Summary of Product Characteristics (updated January 2021). Presented
by system organ class and frequency using the following categories: very common (≥ 1/10);
common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000);
very rare (< 1/10,000). Within each frequency grouping, undesirable effects are presented in
order of decreasing seriousness.
MedDRA System Organ Class Frequency Adverse Reaction
Infections and infestations Common Conjunctivitis
Oral herpes
Blood and lymphatic system Common Eosinophilia
disorders
Immune system disorders Very rare Serum sickness/serum sickness-like reactions
Not known Anaphylactic reaction*
Angioedema*
Nervous system disorders Common Headache
Eye disorders Common Conjunctivitis allergic
Eye pruritus
Blepharitis
Uncommon Keratitis
Ulcerative keratitis
Musculoskeletal and Not known Arthralgia*
connective tissue disorders
General disorders and Very common Injection site reactions
administration site conditions
* From postmarketing reporting
• Report suspected side effects to the MHRA via the Yellow card scheme
(https://yellowcard.mhra.gov.uk/)
18. Dupilumab therapy and ocular side effects
• Eye symptoms are reported as a very common side effect of dupilumab therapy, including,
blepharitis, conjunctivitis and eye pruritus.
• The potential for ocular side effects with dupilumab should be highlighted to and discussed
with the local ophthalmology team, and consider the use of prophylactic treatment with eye
lubricants prior to initiation of dupilumab in all patients in line with local formulary.
• For patients with a known pre-existing ophthalmic condition (e.g. keratoconus or previous
corneal grafts), consider review by an ophthalmologist prior to starting dupilumab to ensure
optimised eye care.
• Patients who develop conjunctivitis that does not resolve following standard treatment or
those who present with severe conjunctivitis (symptoms to consider are significant
conjunctival mucus, severe itch/irritation/watering, worsening conjunctival redness,
pain/photophobia and loss of vision) should undergo ophthalmological examination to
South East London Integrated Medicines Optimisation Committee.
A partnership between NHS organisations in South East London: South East London Clinical Commissioning Group (covering the boroughs of Bexley,
Bromley, Greenwich, Lambeth, Lewisham and Southwark) and GSTFT/KCH /SLaM/ & Oxleas NHS Foundation Trusts/Lewisham & Greenwich NHS Trust
Approved: June 2021 Review Date: June 2022
Not to be used for commercial or marketing purposes. Strictly for use within the NHS. Page 10 of 18exclude infective causes or other potential complications (consider same-day referral to
local Eye Casualty/Ophthalmology service).
19. Dupilumab therapy and musculoskeletal side effects
• Musculoskeletal symptoms are reported as an uncommon (incidence unknown) side effect
of dupilumab therapy, including arthralgia and joint stiffness. This can be due to
inflammatory synovitis and/or enthesitis with symptoms worse on wakening and lasting
more than 30 minutes.
• Patients who develop significant musculoskeletal symptoms should undergo
rheumatological assessment and consider urgent referral to a local rheumatology service.
• The decision to continue dupilumab therapy should be considered on a case-by-case basis.
20. Method of medication supply
Subject to local arrangements patients may be offered a choice of method of supply. This may
include a traditional homecare service or enhanced outpatient pharmacy service via outsourced
outpatient pharmacies on main hospital sites. Where there is agreement with pharmaceutical
companies, unbundling of homecare and direct procurement via outsourced pharmacies may
result in a reduction in the drug acquisition cost.
Subject to local arrangements, in order to reduce the time to initiation with dupilumab, the first
doses (2 – 4 weeks supply) may be given on-site as part of an outpatient biologic initiation service.
As the first dose(s) are administered in the outpatient clinic, the cost will incur VAT and this will
be passed onto commissioners.
21. Monitoring adherence with this pathway
Adherence to this pathway will be reviewed using the SEL Dermatology Pathways, Outcomes and
Monitoring Framework which includes Key Performance Indicators agreed by South East London
Integrated Medicines Optimisation Committee. See http://www.lambethccg.nhs.uk for further details.
The Dermatology and Pharmacy Departments may undertake separate clinical audits as part of their
annual clinical audit plan.
22. Supporting documents (also see relevant local guidelines)
1. Technology appraisal guidance [TA534] National Institute for Health and Care Excellence -
Dupilumab for treating moderate to severe atopic dermatitis. Published date: 01 August 2018
https://www.nice.org.uk/guidance/ta534
2. Summary of Product Characteristics Dupixent® 300mg solution for injection in pre-filled syringe.
Last updated 06 Jan 2021 . https://www.medicines.org.uk/emc/product/8553/smpc
3. Lesham YA, Hajar T, Hanifin JM, Simpson EL. What the EASI score tells us about the severity of
atopic dermatitis – an interpretability study. Br J Dermatol 2015 Jan 12. Doi: 10.1111/bjd.13662
South East London Integrated Medicines Optimisation Committee.
A partnership between NHS organisations in South East London: South East London Clinical Commissioning Group (covering the boroughs of Bexley,
Bromley, Greenwich, Lambeth, Lewisham and Southwark) and GSTFT/KCH /SLaM/ & Oxleas NHS Foundation Trusts/Lewisham & Greenwich NHS Trust
Approved: June 2021 Review Date: June 2022
Not to be used for commercial or marketing purposes. Strictly for use within the NHS. Page 11 of 184. Chopra R et al. Severity strata for Eczema Area and Severity Index (EASI), modified EASI, Scoring
Atopic Dermatitis (SCORAD), Atopic Dermatitis Severity Index and body surface area in
adolescents and adults with atopic dermatitis. Br J Dermatol 2017. Doi.1111/bjd/15641
5. British Association of Dermatologists guidelines for the safe and effective prescribing of oral
ciclosporin in dermatology 2018. https://onlinelibrary.wiley.com/doi/epdf/10.1111/bjd.17587
6. British Association of Dermatologists guidelines for the safe and effective prescribing of
methotrexate for skin disease 2016. https://onlinelibrary.wiley.com/doi/full/10.1111/bjd.14816
7. British Association of Dermatologists’ guidelines for the safe and effective prescribing of
azathioprine 2011. https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2133.2011.10575.x
8. British Association of Dermatologists Patient Information Leaflet: Mycophenolate mofetil
Updated May 2020. www.bad.org.uk/shared/get-file.ashx?id=108&itemtype=document
9. Dupixent : EPAR - Public assessment report (EMA/512262/2017; Last updated:11/10/2017).
https://www.ema.europa.eu/en/medicines/human/EPAR/dupixent
10. Dupixent-H-C-4390-X-0004-G : EPAR - Assessment report - Extension (EMA/188111/2019; First
published:28/06/2019). https://www.ema.europa.eu/en/documents/variation-
report/dupixent-h-c-4390-x-0004-g-epar-assessment-report-extension_en.pdf
11. Department of Health Immunisation against Infectious disease – The Green Book
https://www.gov.uk/government/collections/immunisation-against-infectious-disease-the-
green-book#the-green-book
South East London Integrated Medicines Optimisation Committee.
A partnership between NHS organisations in South East London: South East London Clinical Commissioning Group (covering the boroughs of Bexley,
Bromley, Greenwich, Lambeth, Lewisham and Southwark) and GSTFT/KCH /SLaM/ & Oxleas NHS Foundation Trusts/Lewisham & Greenwich NHS Trust
Approved: June 2021 Review Date: June 2022
Not to be used for commercial or marketing purposes. Strictly for use within the NHS. Page 12 of 18Practical Points for Primary Care
1. Identification of patient on dupilumab treatment
Following communication from the specialist dermatology team (see Appendix 3 for dupilumab
initiation GP letter template) it is the GP’s responsibility to update a patient’s medical record to
state that they are receiving treatment with dupilumab.
2. Vaccinations
Do not give live vaccines to people on biologic therapy such as dupilumab, or to infants (up to 6
months of age) whose mothers have received biologic therapy beyond 16 weeks’ gestation.
Inactivated vaccines are safe to administer concurrently with biologic therapy.
Patients should receive the annual influenza vaccine (intramuscular only), pneumococcal
polysaccharide vaccination (PPV) and COVID-19 vaccine while on dupilumab therapy. The GP
should ensure the patient is flagged as being on immunosuppression and requiring vaccination
according to Department of Health Guidance.
3. Increased risk of infection
GPs must be aware that patients on biologic therapy such as dupilumab are at an increased risk
of infection, particularly oral herpes. They should therefore have a high index of suspicion if a
patient on dupilumab presents with infective signs or symptoms.
4. Patients on dupilumab who have asthma
Dupilumab is also licensed in the UK to treat severe asthma with type 2 inflammation and is
expected to be considered by NICE for this indication. When dupilumab is prescribed for
eczema, the associated benefit in asthma symptoms may lead to changes in asthma therapy
(e.g. inhaler therapy) and both the patient’s primary care and respiratory teams must be
notified.
GPs must be aware of this and make a note in the patient’s medical record that dupilumab also
has a beneficial effect in asthma, and that any changes to or cessation of dupilumab therapy
may adversely affect the patient’s asthma control. Caution is therefore required and an action
plan in these instances is recommended.
5. Ocular symptoms
GPs must be aware of the ocular side effects commonly associated with the use of dupilumab
including symptoms of blepharitis, conjunctivitis and eye pruritus. Any patient on dupilumab
therapy who presents to the GP with new ocular symptoms, must be directed to contact their
specialist dermatology team. If a patient presents with mild conjunctivitis, GPs should prescribe
eye lubricants and/or antihistamine eye preparations as per local guidance or formulary. If a
patient presents with severe symptoms such as significant conjunctival mucus, severe
itch/irritation/watering, worsening conjunctival redness, pain/photophobia and loss of vision
GPs should consider urgent referral to Eye Casualty/Ophthalmology service.
South East London Integrated Medicines Optimisation Committee.
A partnership between NHS organisations in South East London: South East London Clinical Commissioning Group (covering the boroughs of Bexley,
Bromley, Greenwich, Lambeth, Lewisham and Southwark) and GSTFT/KCH /SLaM/ & Oxleas NHS Foundation Trusts/Lewisham & Greenwich NHS Trust
Approved: June 2021 Review Date: June 2022
Not to be used for commercial or marketing purposes. Strictly for use within the NHS. Page 13 of 186. Musculoskeletal side effects
Musculoskeletal symptoms are reported as an uncommon side effect of dupilumab, including
arthralgia and joint stiffness. If a patient on dupilumab treatment presents to their GP with
these symptoms, the patient must be directed by the GP to contact their specialist dermatology
team as soon as possible in order to arrange a review and rheumatological assessment.
7. Pregnancy
If a patient who is receiving dupilumab or who has recently stopped therapy (within 12 weeks of
gestation) reports a pregnancy to the GP, the GP must inform the dermatologist as soon as
possible to arrange urgent follow-up and monitoring.
8. Surgery (elective)
If a patient is due to have elective surgery, advise them to contact their dermatologist/clinical
nurse specialist for advice on when/if to stop therapy prior to surgery.
Dupilumab can be restarted postoperatively if there is no evidence of infection and wound
healing is usually satisfactory.
South East London Integrated Medicines Optimisation Committee.
A partnership between NHS organisations in South East London: South East London Clinical Commissioning Group (covering the boroughs of Bexley,
Bromley, Greenwich, Lambeth, Lewisham and Southwark) and GSTFT/KCH /SLaM/ & Oxleas NHS Foundation Trusts/Lewisham & Greenwich NHS Trust
Approved: June 2021 Review Date: June 2022
Not to be used for commercial or marketing purposes. Strictly for use within the NHS. Page 14 of 18Appendix 1 - Suggested pre-dupilumab screening and monitoring schedule
Investigations Pre-treatment Monitoring
Disease severity assessment*
EASI, DLQI, POEM, Physician’s and Patient’s global YES At 3 – 4 months to establish disease response (NICE
assessments time point; week 16); 6 monthly thereafter
Blood tests**
Full blood count YES At 3 – 4 months of treatment, with further blood test
Creatinine, electrolytes YES within first 12 months of treatment; every 12 – 18
Liver function tests YES months thereafter if stable.
Repeat if change in risk profile
Hepatitis B sAb/sAg/core Ab YES
Hepatitis C IgG Ab YES
HIV Ab YES
Immunoglobulins
IgG, IgM and IgA subsets Only in patients with At 3 – 4 months and then every 12 months until 12
clinical history months after completion of treatment. Refer to
suggestive of clinical immunology if IgG drops below 4g/L and/or
immunodeficiency there is an increased incidence of infections
Identification of cautions to therapy and/or
development of therapy induced toxicity*
Thorough history, symptom enquiry, clinical examination
(including enquiry regarding potential side effects [e.g. YES At 3 – 4 months; 6 monthly thereafter
eye and musculoskeletal symptoms]; full skin check;
assessment for lymphadenopathy)
Infection
Establish any history of herpes simplex infection and YES At 3 – 4 months; 6 monthly thereafter
previous/current need for prophylaxis.
Consider history of helminth infections or foreign travel.
Consider risk factors for tuberculosis; sexual history; drug
abuse; history of blood transfusions; any past or current
chronic infection.
Malignancy
Ensure concordant with national cancer screening YES At 3 – 4 months; every 6 – 12 months thereafter
programmes; any past or current malignancy;
gynaecological review if history of cervical dysplasia;
regular review for skin cancer
Lung Function
Spirometry Patients with severe Please contact appropriate respiratory team who will
Fractional exhaled nitric oxide (FeNO) or unstable asthma perform baseline assessment and monitor patient
within asthma service
*Disease severity assessments and physical examination will depend on mode of clinician review (face-to-face
or virtual) in the context of the COVID-19 pandemic.
**Monitoring requirements may be subject to local rationalised monitoring protocols due to patients’ ability
to attend for blood tests and the availability of local resources, due to COVID-19
South East London Integrated Medicines Optimisation Committee.
A partnership between NHS organisations in South East London: South East London Clinical Commissioning Group (covering the boroughs of Bexley,
Bromley, Greenwich, Lambeth, Lewisham and Southwark) and GSTFT/KCH /SLaM/ & Oxleas NHS Foundation Trusts/Lewisham & Greenwich NHS Trust
Approved: June 2021 Review Date: June 2022
Not to be used for commercial or marketing purposes. Strictly for use within the NHS. Page 15 of 18Appendix 2 – Half Life of Common Treatments
Drug Half-life (hours) Time for 5 half lives
Prednisolone 4 20 hours (1 day)
Methotrexate 10 50 hours (2 days)
Ciclosporin 25 125 hours (5 days)
Mycophenolate Mofetil 18 90 hours (4 days)
Azathioprine 6 30 hours (1-2 days)
When choosing to transition from one systemic therapy to another and whether a therapy washout (or
no washout) should be used, take into consideration:
• the pharmacology of the drugs that are being started and stopped.
• the person’s clinical circumstance.
• the person’s views on the risks and benefits of transitioning option(s).
Consider the following strategies when transitioning from standard systemic to biologic therapy:
• in stable disease, aim not to overlap the current standard systemic immunosuppressant therapy and
the planned dupilumab initiation.
• when standard, systemic immunosuppressant therapy cannot be stopped (e.g. prednisolone in
patients at risk of unstable disease and for whom a disease flare would be severe or hazardous),
rationalize use of therapy and stop soon after initiation of dupilumab.
• care should be taken when weaning/discontinuing prednisolone in those on long term therapy or
likely to experience a disease flare before dupilumab can be initiated – where adrenal insufficiency
is suspected and withdrawal of glucocorticoid therapy is being considered refer to local
guidance/endocrinology opinion.
South East London Integrated Medicines Optimisation Committee.
A partnership between NHS organisations in South East London: South East London Clinical Commissioning Group (covering the boroughs of Bexley,
Bromley, Greenwich, Lambeth, Lewisham and Southwark) and GSTFT/KCH /SLaM/ & Oxleas NHS Foundation Trusts/Lewisham & Greenwich NHS Trust
Approved: June 2021 Review Date: June 2022
Not to be used for commercial or marketing purposes. Strictly for use within the NHS. Page 16 of 18Appendix 3 – Suggested dupilumab initiation letter template to GP
Re: Date of Birth:
Hospital No: NHS No:
Address:
Dear
Your patient was reviewed recently in our dermatology service. The decision was made to start
subcutaneous dupilumab injections (Dupixent®) for severe atopic dermatitis. Dupilumab is a
monoclonal antibody that inhibits interleukin-4 and interleukin-13, and will be prescribed and
supplied via the hospital. Full details of screening and planned treatment are outlined below:
Co-morbidities, allergies and concomitant medication:
Screening results:
Appropriate reference baseline score : EASI= DLQI= POEM=
Planned treatment: Dupilumab subcutaneous injection: 600mg week 0; 300mg week 2; then
300mg every other week thereafter.
Delivery of Dupilumab:
Follow up:
Any other relevant information:
Information for GP:
1. Please ensure that your patient receives the pneumococcal vaccine and annual flu vaccine.
2. Conjunctivitis is a common side effect of dupilumab. Rarely it can be severe and sight
threatening. Any patient on dupilumab therapy who presents to the GP with new ocular
symptoms, must be directed to contact their specialist dermatology team.
For patients with mild conjunctivitis prescribe eye lubricants and/or antihistamine eye
preparations as per local guidance/formulary.
For patients with moderate to severe* conjunctivitis or concerns relating to infection please
refer urgently to your local ophthalmology service.
*Symptoms to consider: significant conjunctival mucus, severe itch/irritation/watering,
worsening conjunctival redness, pain/photophobia and or loss of vision
3. Arthralgia/enthesitis is an uncommon side effect seen with duplimumab – please advise any
patients presenting with these symptoms to contact their dermatology team as soon as
symptoms experienced.
4. Please monitor any co-morbid atopic disease (e.g. asthma) and adjust therapy as required.
Dupilumab also has a beneficial effect in asthma, and any changes to or cessation of
dupilumab therapy may adversely affect the patient’s asthma control. Patients may need to
increase asthma therapy if stopping dupilumab.
Yours sincerely
South East London Integrated Medicines Optimisation Committee.
A partnership between NHS organisations in South East London: South East London Clinical Commissioning Group (covering the boroughs of Bexley,
Bromley, Greenwich, Lambeth, Lewisham and Southwark) and GSTFT/KCH /SLaM/ & Oxleas NHS Foundation Trusts/Lewisham & Greenwich NHS Trust
Approved: June 2021 Review Date: June 2022
Not to be used for commercial or marketing purposes. Strictly for use within the NHS. Page 17 of 18Appendix 4 - Service Quality Standards
Service Statement
Quality
Standard
1 Initiation and supervision of dupilumab therapy for people with atopic dermatitis should be
undertaken by specialist physicians experienced in the diagnosis and treatment of atopic
dermatitis
2 Arrangements for drug administration, monitoring and follow-up should be agreed between
health carers and the person receiving treatment, utilising the support and expertise of a
multidisciplinary team e.g. clinical nurse specialists and specialist pharmacists following locally
agreed protocols.
3 Local arrangements are made to ensure access to a specialist respiratory team who are able to
advise on concurrent asthma management where applicable, and a specialist ophthalmology
team who are able to advise on the use of prophylactic ocular treatments or to refer to in cases
of ocular side effects, including urgent referrals.
4 Provision of biologic therapy via Homecare services is overseen by an appropriate group within
each trust, accountable to the Chief Pharmacist.
All medicines ordered via homecare services are clinically screened and processed via pharmacy.
(DH Report - Homecare Medicines "Towards a vision for the future" November 2011)
Consultation Process
South East London Dermatology Pathway Group (see authors) March and April 2021
South East London Integrated Medicines Optimisation Committee.
A partnership between NHS organisations in South East London: South East London Clinical Commissioning Group (covering the boroughs of Bexley,
Bromley, Greenwich, Lambeth, Lewisham and Southwark) and GSTFT/KCH /SLaM/ & Oxleas NHS Foundation Trusts/Lewisham & Greenwich NHS Trust
Approved: June 2021 Review Date: June 2022
Not to be used for commercial or marketing purposes. Strictly for use within the NHS. Page 18 of 18You can also read
