Horizon Scanning Centre

November 2013

Dimethyl fumarate for plaque

psoriasis
SUMMARY

NIHR HSC ID: 7758

Dimethyl fumarate is intended to be used for the treatment of moderate to

severe plaque psoriasis. If licensed dimethyl fumarate may present an
additional treatment option for this patient group, potentially delaying or
avoiding the need for biological therapies. Dimethyl fumarate is one of three
fumaric acid salts present in Fumaderm, a drug already licensed in Germany
for plaque psoriasis.
This briefing is
based on
information
available at the time
of research and a
limited literature
search. It is not
intended to be a
definitive statement
on the safety,
efficacy or
effectiveness of the
health technology
covered and should
not be used for
commercial
purposes or
commissioning
without additional
information.

Plaque psoriasis is the most common type of psoriasis, representing 90% of

cases. The estimated UK prevalence of psoriasis is 1.5-1.63%, with 1.1% of
suffering with severe disease. It has a bimodal onset, with the first peak
occurring in persons aged 16 to 22 years, and the second in persons aged
57 to 60 years. The prevalence of psoriasis in those younger than 10 years is
estimated to be 0.55% and 1.4% in those aged between 10 and 19 years.
The estimated prevalence of people currently eligible for biological therapy in
England is 1.1% of those with psoriasis. Chronic plaque psoriasis is typified
by itchy, well demarcated circular-to-oval bright red/pink elevated lesions
(plaques) with overlying white or silvery scale, distributed symmetrically over
extensor body surfaces and the scalp. Current treatment options include
topical ointments and emollients, phototherapy, systemic therapies (e.g. oral
retinoids) and biological therapies.
Dimethyl fumarate is currently in a phase III clinical trial comparing its effect
on psoriasis area and severity index (PASI) against treatment with
Fumaderm or placebo. This trial is expected to complete in December 2014.

This briefing presents independent research funded by the National Institute

for Health Research (NIHR). The views expressed are those of the author
and not necessarily those of the NHS, the NIHR or the Department of Health.
NIHR Horizon Scanning Centre, University of Birmingham
Email: nihrhsc@contacts.bham.ac.uk
Web: http://www.hsc.nihr.ac.uk

NIHR Horizon Scanning Centre

TARGET GROUP

Plaque psoriasis: moderate to severe.

TECHNOLOGY
DESCRIPTION
Dimethyl fumarate (LAS-41008) is a methyl ester of fumaric acid. Fumaric acid and its
sodium salts have been previously used in psoriasis, and dimethyl fumarate appears to be
the most active compound when given orally. Dimethyl fumarate inhibits certain functions of
endothelial cells, namely, differentiation, proliferation and migration, as well as affecting the
immune system and proliferating cells in general. Dimethyl fumarate is administered at a
starting dose of 30mg daily, titrated up to a maximum of 720mg daily.
Dimethyl fumarate is also in development for multiple sclerosis. It is also one of three fumaric
acid salts present in Fumaderm, which is currently licensed for the treatment of plaque
psoriasis in Germany.

INNOVATION and/or ADVANTAGES

If licensed dimethyl fumarate may present an additional treatment option for this patient
group, potentially delaying or avoiding the need for biological therapies.

DEVELOPER
Almirall SA.

AVAILABILITY, LAUNCH OR MARKETING

In phase III clinical trials.

PATIENT GROUP
BACKGROUND
Psoriasis is defined as a chronic, inflammatory, multisystem disease with predominantly skin
and joint manifestations 1. It is characterised by scaly skin lesions, which can be in the form
of patches, papules, or plaques. The skin lesions of psoriasis are characterised by1:
Hyperproliferation of the epidermis.
Dilation and proliferation of blood vessels in the dermis.
Accumulation of inflammatory cells, particularly neutrophils and T-lymphocytes.
Chronic plaque psoriasis is typified by itchy, well demarcated circular-to-oval bright red/pink
elevated lesions (plaques) with overlying white or silvery scale, distributed symmetrically
over extensor body surfaces and the scalp 2. Plaque psoriasis may manifest differently in
children plaques may not be as thick, and the lesions may be less scaly. Psoriasis may
also appear in the flexural areas in children and the disease more commonly affects the face
compared with adults 3.

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NHS or GOVERNMENT PRIORITY AREA
None identified.

CLINICAL NEED and BURDEN OF DISEASE

Plaque psoriasis is the most common type of psoriasis, representing 90% of cases. The
estimated UK prevalence of psoriasis is 1.5-1.63% 4,5, with 1.1% of people suffering with
severe disease5. It has a bimodal onset, with the first peak occurring in persons aged 16 to
22 years, and the second in persons aged 57 to 60 years. The prevalence of psoriasis in
those younger than 10 years is estimated to be 0.55% and 1.4% in those aged between 10
and 19 years4,6. The estimated prevalence of people currently eligible for biological therapy
in England is 1.1% of those with psoriasis5. Females typically develop plaque psoriasis
earlier than males, and patients with a positive family history for psoriasis also tend to have
an earlier age of onset4. Acute flares or relapses of plaque psoriasis may evolve into more
severe disease, such as pustular or erythrodermic psoriasis 7. The significant reduction in
quality of life and psychosocial disability suffered by people with psoriasis underlies the need
for prompt, effective treatment, and long-term disease control 8.
In 2011-12, for all age groups there were 13,546 hospital admissions due to psoriasis in
England, equating to 14,094 finished consultant episodes and 23,195 bed days. There were
a total of 356 finished consultant episodes for patients aged up to 14 years in 2011-12 9.

PATIENT PATHWAY
RELEVANT GUIDANCE
NICE Guidance

NICE technology appraisal. Ustekinumab for the treatment of adults with moderate to
severe psoriasis (TA180). September 2009 10.
NICE technology appraisal. Adalimumab for the treatment of adults with psoriasis
(TA146). June 2008 11.
NICE technology appraisal. Infliximab for the treatment of adults with psoriasis (TA134).
January 2008 12.
NICE technology appraisal. Etanercept and efalizumab for the treatment of adults with
psoriasis (TA103). July 2006 13.
NICE clinical guideline. Psoriasis: the assessment and management of psoriasis
(CG153). October 2012 14.

Other Guidance

The Canadian Guidelines for the Management of Plaque Psoriasis. Consensus

guidelines for the management of plaque psoriasis. 2012 15.
American Academy of Dermatology. Guidelines of care for the management of psoriasis
and psoriatic arthritis: section 6. Guidelines of care for the treatment of psoriasis and
psoriatic arthritis: Case-based presentations and evidence-based conclusions. 20111.
SIGN. Diagnosis and management of psoriasis and psoriatic arthritis in adults. 2010 16.
British Association of Dermatologists and Primary Care Dermatology Society. Clinical
guideline: Recommendations for the initial management of psoriasis. 2009 17.

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British Association of Dermatologists' guidelines for biologic interventions for psoriasis.

2009 18.
American Academy of Dermatology. Guidelines of care for the management of psoriasis
and psoriatic arthritis: section 4. Guidelines of care for the management and treatment of
psoriasis with traditional systemic agents. 2009 19.
Pathirana D, Ormerod AD, Saiag P et al. European S3-guidelines on the systemic
treatment of psoriasis vulgaris. 2009 20.
American Academy of Dermatology. Guidelines of care for the management of psoriasis
and psoriatic arthritis: section 1. Overview of psoriasis and guidelines of care for the
treatment of psoriasis with biologics. 20087.

EXISTING COMPARATORS and TREATMENTS

Current treatment options for plaque psoriasis include,15,18,21,22:
Topical (alone or in combination)
Emollients.
Corticosteroids: betamethasone dipropionate.
Vitamin D analogues: calcipotriol, calcitriol, tacalcitol and tazarotene (with or without
phototherapy).
Tars (with or without phototherapy).
Dithranol (with or without phototherapy).
Retinoids: tazarotene.
Salicyclic acid.
Tacrolimus ointment (not licensed for this indication).
Phototherapy
Narrow band UVB and psoralen and UVA combination (PUVA).
Systemic therapies (for the treatment of patients with severe or refractory psoriasis)
Oral retinoids: acitretin (with or without phototherapy).
Hydroxycarbamide (not licensed for this indication).
Fumaric acid esters: monoethylfumarate and dimethylfumarate (licensed in the EU but
not in the UK).
Ciclosporin.
Methotrexate.
Biologics (for the treatment of patients intolerant, contraindicated or refractory to other
treatments)
Drugs affecting the immune response: adalimumab, etanercept, infliximab, and
ustekinumab.

EFFICACY and SAFETY

Trial
Sponsor
Status
Source of
information
Location

NCT01726933, M41008-1102, 2012-000055-13; dimethyl fumarate or Fumaderm vs

placebo; phase III.
Almirall SA.
Ongoing.
23
Trial registry .
EU (not incl UK).

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Design
Participants
Schedule
Follow-up
Primary
outcome/s
Secondary
outcome/s
Expected
reporting
date

Randomised, placebo-controlled.
n=690 (planned); 18 years; moderate to severe plaque psoriasis.
Randomised to oral dimethyl fumarate, at a starting dose of 30mg daily, titrated up to a
maximum of 720mg daily, Fumaderm (dose not reported) or placebo.
Active treatment period 6 weeks, follow-up 12 months thereafter.
Psoriasis area and severity index (PASI) 75; physician global assessment (PGA).
Body surface area; dermatological life quality index; PASI 75 at week 3, 8 and followup; PGA at week 3, 8 and follow-up; adverse events.
Estimated study completion date Dec 2014.

ESTIMATED COST and IMPACT

COST
The cost of dimethyl fumarate is not yet known. The costs of other selected treatments for
severe plaque psoriasis are given below22:
Drug
Adalimumab
(Humira)
Etanercept
(Enbrel)
Infliximab
(Remicade)
Ustekinumab
(Stelara)

Dose
80mg SC; then 40mg SC on
alternate weeks one week
after initial dose.
25mg SC twice weekly or
50mg SC once weekly.
5mg/kg IV repeated at 2 and
6 weeks; then every 8 weeks.
Initially 45mg, then 45mg 4
weeks after initial dose, then
45mg every 12 weeks.

Unit Cost
352 (40mg, prefilled
syringe)

Annual cost
9,504

89 (25mg, prefilled
syringe)
420 (100mg vial)

9,256

2147 (45mg, prefilled

syringe)

10,735

11,760

IMPACT - SPECULATIVE
Impact on Patients and Carers
Reduced mortality/increased length of survival

Reduced symptoms or disability

Other

No impact identified

Impact on Services
Increased use of existing services

Decreased use of existing services: oral

treatment option. Fumaderm is also currently
used off-licence in most UK departments to
control chronic plaque psoriasis. This may
negate the need for specialist training in order
b
to initiate and prescribe this therapy .

Re-organisation of existing services

Need for new services

Other

None identified

a Based
b

on an average body weight of 77.9kg.

Expert personal communication.

NIHR Horizon Scanning Centre

Impact on Costs
Increased drug treatment costs

Reduced drug treatment costs

Other increase in costs

Other reduction in costs

Other: uncertain unit cost compared to

existing treatments.

None identified

Other Issues
Clinical uncertainty or other research question
identified: Expert opinion suggests it would be
beneficial to have more data on the efficacy of
dimethyl fumarate in a paediatric population
and to determine how immunosuppressive the
therapy is in relation to other systemic agents
for plaque psoriasis (e.g. methotrexate).
There are also a number of other oral drugs in
c
development for plaque psoriasis .

None identified

REFERENCES
1

American Academy of Dermatology. Guidelines of care for the management of psoriasis and
psoriatic arthritis: Section 6. Guidelines of care for the treatment of psoriasis and psoriatic arthritis:
case-based presentations and evidence-based conclusions. Journal of the American Academy of
Dermatology 2011;65(1):137-74.
2
Patient.co.uk. Chronic Plaque Psoriasis. October 2011. http://www.patient.co.uk/doctor/chronicplaque-psoriasis.htm Accessed 16 April 2013.
3
Lui H and Mamelak AJ. Plaque Psoriasis. Medscape reference: Drugs, diseases and procedures.
March 2011. http://emedicine.medscape.com/article/1108072-overview Accessed 8 September
2013.
4
Gelfand JM, Weinstein R, Porter SB et al. Prevalence and treatment of psoriasis in the United
Kingdom: a population-based study. Archives of Dermatology 2005;141(12):1537-41.
5
National Institute for Health and Clinical Excellence. Costing statement: ustekinumab for the
treatment of adults with moderate to severe psoriasis. London: NICE; September 2009.
http://www.nice.org.uk/nicemedia/live/12235/45509/45509.pdf
6
Chaplin S and Atherton D. Etanercept: a new option in paediatric plaque psoriasis. Future
Prescriber 2009;9(3):6-10.
7
American Academy of Dermatology. Guidelines of care for the management of psoriasis and
psoriatic arthritis: Section 1. Overview of psoriasis and guidelines of care for the treatment of
psoriasis with biologics. Journal of the American Academy of Dermatology 2008;58(5):826-50.
8
NIHR Horizon Scanning Centre. Tofacitinib for moderate to severe chronic plaque psoriasis
second line. University of Birmingham, November 2012. http://www.hsc.nihr.ac.uk
9
NHS Hospital episode statistics. NHS England 2011-12 HES data. 2012. www.hesonline.nhs.uk
10
National Institute for Health and Clinical Excellence. Ustekinumab for the treatment of adults with
moderate to severe psoriasis. Technology Appraisal TA180. London: NICE; September 2009.
11
National Institute for Health and Clinical Excellence. Adalimumab for the treatment of adults with
psoriasis. Technology appraisal TA146. London: NICE; June 2008.
12
National Institute for Health and Clinical Excellence. Infliximab for the treatment of adults with
psoriasis. Technology appraisal TA134. London: NICE; January 2008.
13
National Institute for Health and Clinical Excellence. Etanercept and efalizumab for the treatment of
adults with psoriasis Technology appraisal TA103. London: NICE; July 2006.
14
National Institute for Health and Clinical Excellence. Psoriasis: the assessment and management of
psoriasis. Clinical guideline CG153. London: NICE; October 2012
15
Hsu S, Papp KA, Lebwohl MG et al. Consensus guidelines for the management of plaque
psoriasis. Archives of Dermatology. 2012;148:95-102.
c

Expert personal communication.

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16

Scottish Intercollegiate Guidelines Network. Diagnosis and management of psoriasis and psoriatic
arthritis in adults. National clinical guideline 121. Edinburgh: SIGN; October 2011.
17
British Association of Dermatologists & Primary Care Dermatology Society. Recommendations for
the initial management of psoriasis. October 2009.
http://www.bad.org.uk/Portals/_Bad/Guidelines/Clinical%20Guidelines/BADPCDS%20Psoriasis%20reviewed%202010.pdf Accessed 9 September 2013.
18
Smith CH, Anstey AV, Barker JN et al. British Association of Dermatologists' guidelines for biologic
interventions for psoriasis 2009. British Journal of Dermatology 2009;161(5):987-1019.
19
American Academy of Dermatology. Guidelines of care for the management of psoriasis and
psoriatic arthritis: Section 4. Guidelines of care for the management and treatment of psoriasis with
traditional systemic agents. Journal of the American Academy of Dermatology 2009;61(3):451-85.
20
Pathirana D, Ormerod AD, Saiag P et al. European S3-guidelines on the systemic treatment of
psoriasis vulgaris. Journal of the European Academy of Dermatology and Venereology 2009;23
Suppl 2:1-70.
21
National Institute for Health and Clinical Excellence. Psoriasis: final scope. London: NICE;
December 2010 http://www.nice.org.uk/nicemedia/live/12344/52350/52350.pdf
22
British Medical Association and Royal Pharmaceutical Society of Great Britain. British National
Formulary. BNF 63. London: BMJ Group and RPS Publishing, March 2013.
23
ClinicalTrials.gov. LAS41008 in moderate to severe chronic plaque psoriasis.
http://clinicaltrials.gov/show/NCT01726933 Accessed 9 September 2013.