Special Thanks - BC Pharmacy Association

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Special Thanks - BC Pharmacy Association
08/05/2014
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8 May 2014
p. 01
Dermatology for Pharmacists:
1. Optimizing psoriasis therapy –
the patient’s perspective
2. Identifying and counselling
patients with actinic keratoses
(Simon) Se Mang Wong, MD, FRCPC
Special Thanks
• Dr. Chih-ho Hong, MD FRCPC
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


Share information about the physiological,
psychosocial and quality-of-life impacts of
psoriasis
Review the importance of the mechanisms of
action of the psoriasis treatment options
Discuss how to select appropriate therapy based
on targeted mechanisms of action and Canadian
psoriasis guidelines
1
08/05/2014
Psoriasis
• A chronic skin disease that affects 2-3% of the
Canadian population (approximately
1,000,000 individuals)
• Can begin at any age
– Most commonly starts in early adulthood OR in
middle age
• Males and females equally affected
Psoriasis
• “skin growing too quickly”
• Underlying factors triggering psoriasis are complex
– Genetics
– Immunologic factors
• Significant improvement in last 10 years, but still a long way to go
• It is not related to:
–
–
–
–
Poor hygiene
An infection
An allergy
Foods
Psoriasis
• Can affect any part of the body
– Scalp, elbows, knees commonly affected
– More severe sites include face, hands, genitalia
• Lesions appear as red to pink thickened areas
with scale (dry skin) overtop
2
08/05/2014
Psoriasis
• 30% of patients will
have underlying joint
inflammation
Psoriatic Arthritis
3
08/05/2014
Psoriasis patients
• More likely to:
– Have type 2 diabetes
– Be overweight
– Be smokers
– Have heart disease, heart attacks, and strokes
– Be depressed
Psoriasis : A multifaceted, systemic,
inflammatory disease
Nail psoriasis
Scalp psoriasis
Psoriatic
arthritis
Disease severity
plaques
Psoriasis –
Systemic inflammatory condition
Psychological
co-morbidities
Metabolic
co-morbidities
Low quality
of life
11
Slide courtesy of Prof Kristian Reich, M.D.
Severity of psoriasis
• % body surface area affected (BSA)
– Mild : < 5%
– Moderate : 5-10%
– Severe : > 10%
• Disease activity (PASI)
– Assesses degree of
• Redness of plaques
• Thickness of plaques
• Scaling of plaques
Distribution of psoriasis severity. Available at: en.wikipedia.org/wiki/Psoriasis
Canadian Guidelines for the management of plaque psoriasis, 1st edition, June 2009.
4
08/05/2014
Psoriasis Disease Severity
•
Psoriasis can have a serious impact even if it involves a small area, such as the
palms of the hands or soles of the feet1
•
Severity of psoriasis is linked to the ways in which the disease impacts daily
activities and quality of life2,3
1.
National Psoriasis Foundation: Statistics 2003
2. Krueger GG, et al. J Am Acad Dermatol 2000;43:281
3. Callen JP, et al. J Am Acad Dermatol 2003;49:897
Body Surface Area – Two Methods for
Estimation
– BSA – the amount of affected skin is measured just in that part of the
body and a score from 1 to 6 is assigned
Score
0-9%
10-29%
30-49%
50-69%
70-89%
90-100%
1
2
3
4
5
6
– “Eyeball” assessment of BSA
• Useful when larger areas are involved
• More frequently employed by experienced evaluators
– Palm assessment of BSA
• Useful for smaller areas of involvement or widely spaced areas
• More frequently employed by new evaluators
1. Finlay AY. Br J Dermatol. 2005;152:861-7.
Body Surface Area – Palm Method
Area of palm plus 5 fingers ≈ 1% of
total BSA1
• Head and Neck = 10% (10 palms)
• Upper extremities = 20% (20 palms)
• Trunk (axillae and groin) = 30% (30
palms)
• Lower extremities (buttocks) = 40%
(40 palms)
• Total BSA = 100% (100 palms)
~1% BSA
1. Finlay AY. Br J Dermatol. 2005;152:861-7.
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08/05/2014
What Does the DLQI Mean ?
• Dermatology Life Quality Index (DLQI) is a simple 10
question dermatology specific quality of life measurement
instrument
• Patient QoL status based on following cut points2
DLQI Score
1Reich
HRQoL Status
0–1
No effect of disease on patient’s life
2–5
Small effect
6–10
Moderate effect
11–20
Very large effect
21–30
Extremely large effect
K, et al. Br J Dermatol. 2006;154:1161-1168; 2Hongbo Y, et al. J Invest Dermatol. 2005;125:659-664.
Psoriasis Treatment
• Three main groups of treatments
– Topical Treatments
– Ultraviolet light based treatment
– Medications taken internally (pills/shots)
• No therapy is curative for psoriasis – it works
only as long as it is taken/used
Treatment for psoriasis
• May follow a traditional
“stepwise” approach or be
customized to patient’s severity
and personal history
• Topical medications
– Cortisone creams, Vit D
– Shampoos for scalp
• Phototherapy
– PUVA
– UVB
Menter A & Griffiths CEM. Current and future management of psoriasis. Lancet 2007; 370: 272-284.
Schematic of psoriasis treatment ladder. Available at : en.wikipedia.org/wiki/Psoriasis
6
08/05/2014
Topical Therapy
• Most patients treated with topical therapies
– Coal tar
– Cortisone containing creams/ointments/lotions
– Vitamin D containing preparations
– Combinations
• Most appropriate for those with mildmoderate, limited disease
• Form foundation of treatment for moderate –
severe disease
Challenges in Psoriasis
Management
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• 2009 Canadian PSO Guidelines encourage
PSO management to be patient-centered:
◦ Treatment should effective, safe, and suited to
the symptoms that the patient presents
◦ Treatment choice should be one that the
patient is most likely to use consistently, over
the long term, to achieve and maintain control
of condition
For current Topical users, reasons for non-compliance mainly to do with
using treatment only when they think necessary, being forgetful of
treatment, its level of inconvenience and “yuckiness”
Reasons for Non-Compliance – Topical – Based on 60% Not Compliant
I only use it when I need to
I would forget to use or take it
I was just told to take the treatment
It is not convenient
Too messy/oily/sticky to apply
It is too expensive
It takes too much time to apply/to take
Not effective/No longer as effective
Too messy more a
problem in Canada
(vs 16%)
I am already taking too many medications
The treatment works if I use more of it
The treatment works if I use less of it
My doctor was not able to provide a clear cause for my
psoriasis
Showing 10% and above
Q32e Why are you not taking [INSERT TREATMENT FROM Q30] according to your
doctor’s instructions? Topical Base: 103
Qx
21
Note: Boxes around data identify topics mentioned in headline
7
08/05/2014


Impact of even mild psoriasis on quality of
life can be profound
Psoriasis has been associated with:
◦ Sleep problems
◦ Difficulty with normal daily activities (e.g.,
handshakes, gym changing rooms, visits to the
hairdresser/barber)
◦ Personal and social problems (e.g., dating, public
speaking)
Canadian Guidelines for the Management of Plaque Psoriasis
Lynde CW et al, 2009
Physical component summary score*
Mental component summary score*
70
60
40
30
20
10
Score out of 100
50
0
Psoriasis
Cancer
Diabetes
Depression
Healthy
adults
*Non-disease-specific measure of health-related quality of life. A higher score represents a
higher quality of life.
Rapp SR et al, 1999
•
Mild to moderate, uncomplicated plaque psoriasis
can be safely managed in primary care
• Identify therapies that are effective, safe and suited
to patient’s symptoms
• Choose therapy that patient is most likely to use
consistently over the long term
•
•
Early, appropriate treatment from primary care
physicians may have a significant positive impact on
disease severity, comorbidities and QoL
More severe cases may require referral
Canadian Guidelines for the Management of Plaque Psoriasis
8
08/05/2014


Emollients to help restore the skin’s natural
barrier
Recognition and avoidance of triggers
◦
◦
◦
◦
◦
◦
Physical trauma
Cold weather
Alcohol consumption
Emotional stress
Streptococcal throat infection
Overexposure to direct sunlight/UV light
(i.e., sunburn)
Canadian Guidelines for the Management of Plaque Psoriasis
Severity
Treatment options
Mild
• Topical calcipotriol/betamethasone dipropionate
combination (Grade A)
• Topical corticosteroids (Grade A)
• Topical calcipotriol (vitamin D 3 analogue) (Grade
A)
• Topical calcitriol (vitamin D 3 analogue)*
Moderate/
severe
• Topical calcipotriol/betamethasone dipropionate
combination
• Oral systemic agents (acetretin, cyclosporine,
methotrexate)
• Oral biologic agents (adalimumab, etanercept,
infliximab)
• Phototherapy (UVB or PUVA)
*Since publication of these guidelines, topical calcitriol has been approved by Health Canada for the
treatment of mild to moderate plaque psoriasis.
PUVA = psoralen + UVA
Canadian Guidelines for the Management of Plaque Psoriasis
Vitamin D 3 analogue
(calcipotriol, calcitriol)
• Reduces keratinocyte
proliferation
• Induces keratinocyte
differentiation
Calcipotriol/betamethason
e dipropionate
combination
• Reduces keratinocyte
proliferation
• Induces keratinocyte
differentiation
• Reduces inflammation
and itchiness
• Has vasoconstrictive
properties
Topical corticosteroids
Reduce inflammation
and itchiness
Canadian Guidelines for the Management of Plaque Psoriasis; Calcipotriol product monograph 2007; Calcipotriol/betamethasone dipropionate product
monograph 2008; Calcitriol product monograph 2009; Guenther LC, Skin Ther Lett 2002.
9
08/05/2014
Starting with a mild potency topical steroid:
•
•
Leads to treatment failure and disappointment
Negatively affects adherence
Corticosteroid type
Name
Very potent
Clobetasol propionate
Halobetasol propionate
Potent
Betamethasone dipropionate
Desoximetasone
Fluocinonide
Fluocinolone acetonide
Mometasone furoate
Moderately potent
Betamethasone valerate
Fluticasone propionate
Triamcinolone acetonide
Weak potency
Hydrocortisone valerate
Hydrocortisone acetate
Zaghloul et al. Arch Dermatol 2004; Health Canada, Drug Product Database



Calcipotriol and calcitriol
Dosage limited by systemic effects on
calcium metabolism
Can cause irritation; not recommended
for facial use
Canadian Guidelines for the Management of Plaque Psoriasis;
Calcipotriol product monograph, 2007; Calcitriol product monograph, 2009.


Fixed-dose combination of calcipotriol
plus betamethasone dipropionate
Combination offers:
◦ Faster response than either component alone
◦ Reduced likelihood of skin irritation,
compared to calcipotriol alone
Canadian Guidelines for the Management of Plaque Psoriasis.
10
08/05/2014

Canadian psoriasis guidelines suggest
combining therapies with distinct targets
or complementary mechanisms of action
◦ Different topicals
◦ Phototherapy plus topical or systemic
(photochemotherapy)
◦ Biologics plus other therapies
Canadian Guidelines for the Management of Plaque Psoriasis
“[Patients should] explore all appropriate choices, to identify
ones that can be used over the long term to achieve and
maintain adequate control of their psoriasis.” Guidelines, p.34

Canadian psoriasis guidelines
distinguish between treatments that
work and treatments the patient will
work with

Recommendations for improved
treatment adherence:
◦ Acceptable formulation, dosing regimen
◦ Frequent follow-up
◦ Physician engagement
Canadian Guidelines for the Management of Plaque Psoriasis
New Option - Dovobet® Gel
Calcipotriol and betamethasone dipropionate gel
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• Two Indications in Canada
i. moderate to severe scalp psoriasis vulgaris
in patients 18 years and older for up to 4
weeks.
ii. mild to moderate plaque psoriasis vulgaris
on the body in patients 18 years and older
for up to 8 weeks
11
08/05/2014
Dovobet® Gel
INDICATIONS AND CLINICAL USE:
Dovobet® Gel is indicated for the topical treatment of:
• moderate to severe scalp psoriasis vulgaris in patients 18 years and
older for up to 4 weeks. (Jan 2009)
• mild to moderate plaque psoriasis vulgaris on the body in patients
18 years and older for up to 8 weeks (Feb 2013)
Active Ingredients: Dovobet ® Gel and Ointment: 50 mcg/g calcipotriol
and 0.5 mg/g betamethasone (as dipropionate)
Formulation:
• Dovobet® Gel: Lipophilic (liquid paraffin, caster oil), non-alcohol base
• Dovobet® Ointment : Oleaginous (paraffin) base
Dovobet (calcipotriol and betamethasone dipropionate) Gel, Product Monograph 08 Feb 2013, LEO
Pharma Inc, Thornhill, ON.
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Dovobet ® Gel
Clinical Efficacy Data
Dovobet® Gel – Body Indication
Pivotal Phase III Study
36
• Multicentre, prospective, randomized, double-blind, 8
week clinical study in patients with mild to moderate
psoriasis
• Compare the efficacy and safety of once daily
treatment of Dovobet® gel with betamethasone gel,
calcipotriol gel, and gel vehicle in subjects with
psoriasis vulgaris on the body
• Primary Endpoint: Patients with Controlled Disease
Menter A, Gold LS, Bukhalo M, Grekin S, Kempers S, Boyce BM, et al. Calcipotriene plus betamethasone
dipropionate topical suspension for the treatment of mild to moderate psoriasis vulgaris on the body: a
randomized, double-blind, vehicle-controlled trial. J Drugs Dermatol. 2013 Jan 1;12(1):92-8.
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Study Outcomes and Conclusion
LEO80185
Subjects With Controlled Disease (%)
80
Betamethasone dipropionate
Calcipotriol
Results
Vehicle
IGA Improvement Over Weeks 1-8
70
37
•
60
%age of subjects with
“controlled disease” over time
50
Dovobet® Gel
40
30.9
30
23.7
20
BDP
23.9
17.1
14.1
10
1.7
0
1
6.7
Week
2
Calcipotriol
7.8Placebo
4
6
8
• At wk 8 a significantly greater
# of subjects on Dovobet ®
gel achieved controlled
disease vs all other
comparators
• No differences in adverse
events between all groups
Conclusion: Dovobet® Gel is an efficacious and safe treatment
for psoriasis that also improves quality of life, in patient with
mild to moderate psoriasis
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Dovobet® Gel
“The Plaque Test”
• Comparative Efficacy:
• Dovobet® Gel vs Dovobet® Ointment
“Plaque Test” Efficacy Data
39
Study compared the antipsoriatic effect of 6 different topical products in
24 patients using a modified version of the psoriasis plaque test
•
•
•
•
•
•
Dovobet® gel (calcipotriol + betamethasone dipropionate)
Dovobet® ointment (calcipotriol + betamethasone dipropionate)
Dovonex® ointment (calcipotriol)
Dovonex® cream (calcipotriol)
Investigational ointment (calcipotriol + hydrocortisone)
Vehicle ointment
Primary endpoint
Absolute change of Total Clinical Score (TCS)
• erythema, scaling, infiltration
Queille-Roussel C, Hoffmann V, Enevold A, Ganslandt C. Use of a psoriasis plaque test in the development of a gel formulation
of calcipotriol and betamethasone dipropionate for scalp psoriasis. The Journal of dermatological treatment. 2011 Dec 21.
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Plaque Test Efficacy Data
Results and Conclusion
Results:
• Dovobet® gel and Dovobet® ointment were significantly more effective
in the reduction of TCS vs all other treatments (p<0.001)
• No significant difference in the reduction of TCS between Dovobet ® gel
and Dovobet® ointment (-5.73 vs -6.19; p = 0.23)
Conclusions:
• Based on the plaque test:
◦ Dovobet® gel and ointment had a comparable efficacy, and were
superior to the other products
◦ Dovobet® gel could provide an alternative effective treatment option to
the well established Dovobet® ointment patients
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Dovobet ® Gel
Patient Use and Acceptance Data
Dovobet® Gel – Patient Use and Acceptance Data
Practicability of combined treatment with Dovobet® Gel and improvement in
QoL in Patients with Psoriasis
42
Non-interventional, cohort study examined real life use
and acceptance of Dovobet® Gel in 579 patients with
mild to moderate psoriasis
•
•
•
•
Compare Dovobet ® Gel to previous therapy
Quality of Life
Burden of Treatment
Assess ease of Medication use
Sticherling M, Eicke C, Anger T. Practicability of combined treatment with calcipotriol/betamethasone gel (Daivobet ® Gel) and
improvement of quality of life in patients with psoriasis. JDDG J German Soc Dermatol 2013; (Published online 26-02-2013
doi:10.1111/ddg.12029): 8 p.
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08/05/2014
Dovobet® Gel – Patient Use and Acceptance Data
Practicability of combined treatment with Dovobet® Gel - QoL in
Psoriasis Patients
Results:
• Significant improvement in QoL
• Rx application time 30%
• Time for “Ready to Dress 22%
• Convenience of use showed 66.1% pts “very satisfied”
with vs 11.6% with prior Rx
• Handling: ~80% of patients rated Dovobet® Gel as
“more” to “much more” pleasant than prior treatment
• Disease severity improved as rated by physicians and
patients (PGA)
Conclusions:
• Treatment with Dovobet® Gel had clinical effects associated with a significant
improvement in QoL
• Patients benefit from the convenience and time-saving compared to prior Tx
• Dovobet® Gel can be recommended as an effective and well-tolerated treatment
which may easily be integrated into daily life of patients with psoriasis.
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Topical Psoriasis Therapy
Factors Affecting Patient Adherence
Patient Adherence
8 May 2014
p. 045
Adherence in Psoriasis Patients is generally poor
• Approximately 50% of patients fail to fill first time prescriptions
• Overall adherence ranges from 22 to 62%
Patient Related Factors
• Age,
• Impact of Disease on Quality of Life
• Psycho-Social and Economic factors
• Patient –HCP relationship
Treatment Related Factors:
• Treatment type
• Time point in treatment history, duration of treatment
• Frequency, Ease/Complexity of regimen
• Impact on daily life
• Adverse effects
Bewley A, Page B. Maximizing patient adherence for optimal outcomes in psoriasis. Journal of the European Academy of
Dermatology and Venereology : JEADV. 2011 Jun;25 Suppl 4:9-14
Thorneloe RJ, Bundy C, Griffiths CEM, Ashcroft DM, Cordingley L. Adherence to Medication in patients with psoriasis: A
systematic literature review. Br J Derm 2013:168:20-31.
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Adherence
Treatment Related Factors: Formulation
Cosmetic acceptability of the formulation
• Greasiness, Messy, Sticky
Ease of Use/Convenience
• Spreadability, Time required for application/drying
A survey in 483 psoriasis patients demonstrated dissatisfactions with
therapy due to slow absorption, application frequency greater than
once-daily and staining of clothes/bedding.
A study in 1281 psoriasis patients showed noncompliance was related
to treatment being unpleasant to use, too time consuming, ineffective
Encouraging Adherence with Topical
Medications
Goal in selecting a topical therapy
• Efficacious
• Safe
• Simple to Use
• Less burdensome
• Cosmetically acceptable
• Patient Preference
Serup J, Lindblad AK, Maroti M, Kjellgren KI, Niklasson E, Ring L, Ahlner J. To follow or not to follw
dermatological treatemtn – a review of the literature. Acta Derm Venereol. 2006;86(3):193-7.
Actinic Keratosis: New Solutions
for The Primary Care Physician
Patient Cases
®
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08/05/2014
Learning Objectives
After attending this session,
participants will be able to:
• Explain the link between actinic
keratosis (AK) and
non-melanoma skin cancers (NMSC)
• Identify the clinical signs and
symptoms of actinic keratosis lesions
• Describe current treatment options for
actinic keratosis
Discussion Question
1. True or false: There is a link
between actinic keratosis and nonmelanoma skin cancer.
A. True
B. False
Actinic Keratoses and
Non-melanoma Skin Cancer
• AK is pre-cancerous skin lesion1,2
• Non-melanoma skin cancer (NMSC)
includes squamous cell carcinoma
(SCC) and basal cell carcinoma
(BCC)
◦ NMSC is the most common type of cancer3
1.
2.
3.
4.
Criscione VD, et al. Cancer. 2009;115(11):2523-30.
Lober BA, et al. South Med J. 2000;93:650-5.
Rogers HW, et al. Arch Dermatol. 2010;146(3):283-7.
Chen J, et al. J Natl Cancer Inst. 2008;100:1215-22.
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08/05/2014
Actinic Keratoses and NMSC
SCC
• AK lesions may progress to
SCC1-3
• AK lesions and SCC are
frequently contiguous as they
share the same genetic
alterations and morphology5,6
1.
2.
3.
4.
5.
6.
Marks R, et al. Lancet. 1988;1:795-7.
Mittelbronn MA, et al. Int J Dermatol. 1998;37:677-81.
Dinehart SM, et al. Cancer. 1997;79:920-3.
Criscione VD, et al. Cancer. 2009;115(11):2523-30.
Berman B, et al. J Fam Pract. 2006;55(5):suppl 1-8.
Feldman SR, et al. Cutis. 2011; 87:201-7.
© Diepgen TL, Yihune G, et al. Dermatology Online Atlas.
AK
Natural History of AK Lesions
• Natural course of AK lesions is
unpredictable1-5
◦ Estimates of 40 to 80% of cutaneous SCCs
arise from, or near, an AK lesion2-5
• AK lesions may persist, regress, or
progress1,3
1.
2.
3.
4.
5.
Criscione VD, et al. Cancer. 2009;115(11):2523-30.
Feldman SR, et al. Cutis. 2011;87(4):201-7.
Marks R, et al. Lancet. 1988;1(8589): 795-7.
Mittelbronn MA, et al. Int J Dermatol. 1998;37:677-81.
Dinehart SM, et al. Cancer. 1997;79:920-3.
Discussion Question
2. Which of the following is not a risk
factor for development of actinic
keratosis lesions?
A.
B.
C.
D.
E.
F.
G.
Male gender
Light-coloured eyes and hair
Cumulative exposure to UV radiation
Excessive/habitual alcohol consumption
Fair skin
Immunosuppression
All of the above are risk factors
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08/05/2014
General Risk Factors for AK
• High intensity or cumulative exposure to UV
radiation1,2
• Use of tanning beds or sunlamps3
• Prior history of AKs or other skin cancer4
• Clinical signs of photodamage, such as
solar/senile lentigines, facial telangiectasia, and
actinic elastosis of the neck4
• Immunosuppression5
• Human papillomaviruses may play a role in
etiology
of AKs5
1.
2.
3.
4.
5.
Diepgen TL, et al. Br J Dermatol.2002;146(suppl 61):1-6.
Berman B, et al. J Fam Pract. 2006;55(5):suppl 1-8.
Hemminki K, et al. Arch Dermatol. 2003;139:885-9.
Feldman SR, et al. Cutis. 2011;87(4):201-7.
Goldberg LH, et al. J Drugs Dermatol. 2010;9(9):1125-32.
Red or
blond hair
Male gender
Light-coloured eyes
Fair skin
Older age, especially
those age 50 years and
older
… But also seen in
individuals aged 20 to
50 years
Individual Susceptibility Factors for AK
Salasche SJ. J Am Acad Dermatol. 2000;42(1 Pt 2):4-7.
Individual Susceptibility
Factors for AK
1
1
2-4
Classification
Response to UV rays
Skin colour
I
Never tans, always burns
White
II
Tans with difficulty, usually burns
White
III
Average tanning, sometimes burns
White
IV
Easily tans, rarely burns
Moderate Brown
V
Very easy to tan, very rarely burns
Hispanic, Latin, African, Asian, Indian
VI
Never burns
Black
1. Fitzpatrick TB. J Med Esthet. 1975;2:33034. 2. Sng J, et al. J Am Acad Dermatol. 2009;61(3):426-32.
3. Ahluwalia J, et al. J Drugs Dermatol. 2012;11(4):484-6. 4. Davis SA, et al. J Drugs Dermatol. 2012;11(4):466-73.
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08/05/2014
Clinical Signs of Actinic
Keratosis Lesions
• Visible/detectable lesions are
reddish to reddish brown,
rough, scaly patches less than
1 cm in diameter1
• Non-visible, non-palpable
lesions occur up to 10 times
more often than visible lesions,
particularly in sun-damaged
skin2
◦ >80% of all AK lesions are
found on sun-exposed areas of
the body3
1.
2.
3.
4.
© DermNet NZ; dermnetnz.org.
When one AK is seen, assume
that other,
perhaps non-visible,
AK lesions exist4
Ulrich M, et al. Dermatology. 2010;220(1):15-24.
Berman B, et al. Expert Opin Pharmacother. 2009;10(18):3015-31.
Salasche SJ. J Am Acad Dermatol. 2000;42(1 Pt 2):4-7.
Berman B, et al. J Fam Pract. 2006;55(5):suppl 1-8.
Clinical Signs of Actinic
Keratosis Lesions
• Lesions can often be felt more
easily than seen1
• Red, rough, scaling spots2
• White scale over a pink
macule or papule1
• Pinhead to 4–5 mm in
diameter1
• Distribution: solitary, clustered,
or disseminated1
• Generally asymptomatic1,2
© DermNet NZ; dermnetnz.org.
1. Stulberg D, et al. Am Fam Physician. 2004;70(8):1481-8.
2. Canadian Dermatology Association. Actinic keratoses fact sheet. 2012.
Examples of AK Lesions
Photos: © DermNet NZ; dermnetnz.org.
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08/05/2014
Lesion-directed
Treatment Options
• Physically destructive methods
◦ Cryosurgery
◦ Laser ablation
• Surgical removal
◦ Shave excision
◦ Curettage
◦ Electrodessication
de Berker D, et al. Br J Dermatol. 2007;156:222-30.
Actinic Keratosis Is a
Field Disease
• Field of cancerisation surrounds clinical
AK lesions and is partially or
completely clinically invisible –
multifocal, paraneoplastic, subclinical
changes1
Clinical lesions
• Histopathology of AKs is found in
surrounding skin2
• Subclinical (non-palpable, non-visible)
AK lesions occur ~10 times more often
than clinical AK lesions in sundamaged skin3
Subclinical lesions
1. Vatve M, et al. Br J Dermatol. 2007;157(Suppl 2):21-4.
2. Berman B, et al. Exp Opin Pharmacother. 2009;10(18):3015-31.
3. Braakhuis BJM, et al. Cancer Res. 2003;63(8):1727-30.
Is Field Treatment the Necessary
Approach?
• It is impossible to know which AK lesions will
progress to invasive SCC, so it is recommended that
all AK lesions be treated1
• The ultimate goal of treatment is to clear the entire
actinically damaged field2
◦ Addressing both clinical and non-visible lesions
may significantly reduce recurrence rates of AK2
• Early diagnosis and treatment of the field of actinic
damage decreases overall disease burden and helps
to prevent development of invasive SCC1,2
1. Martin G. J Clin Aesthet Dermatol. 2010;3(11):20-5.
2. Ulrich M, et al. Exp Opin Emerg Drugs. 2010;15(4):545-55.
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Field-directed Topical Treatment
Options
Treatment
Dosing
Duration of treatment
5-fluorouracil (5-FU)1
Twice daily
Usual duration: 2-4 weeks
Imiquimod 3.75% (face, balding
scalp)2
Up to 2 packets once daily
6 weeks (2 treatment cycles of 2
weeks, separated by a 2-week
no-treatment period)
Imiquimod 5% (face, balding scalp)3
Twice weekly
16 weeks
Ingenol mebutate 0.015% (face,
scalp)4
Once daily
3 consecutive days
Ingenol mebutate 0.05% (trunk,
extremities)4
Once daily
2 consecutive days
Aminolevulinic acid5 or methyl
aminolevulinate6 with PDT
Agents applied a day5 or a few
hours6 before light treatment
15 to 26 treatment cycles
May be retreated 8+ weeks5 or
3+ months6 after initial treatment
1. EFUDEX® product monograph, 2004. 2. ZYCLARA ® product monograph, 2012.
3. ALDARA® product monograph, 2012. 4. PICATO® product monograph, 2013.
5. Levulan Kerastick® product monograph, 2004. 6. METVIX™ product monograph, 2009.
Efficacy of Field-directed Topical
Therapies
Treatment
Complete
clearance,
% patients
Follow-up
period
Patients with
sustained
clearance, %
Follow-up
period
48–58%1-3
4 weeks
54%4
5-FU
12 months
Imiquimod 3.75%*
36%5
8 weeks
41%6
12 months
Imiquimod 5%7*
45%
8 weeks
43%
12-18 months
Ingenol mebutate 0.015%*8
42%
57 days
46%
12 months
Ingenol mebutate 0.05%8
34%
57 days
50%
12 months
47–82%9-11
1–3 months
40%9
12 months
Photodynamic therapy
(PDT)
Between-study comparisons are not intended due to differences in patient demographics and other study parameters.
*Indicated for face and scalp only.
1. Jorizzo J, et al. Cutis. 2002;70(6):335-9. 2. Weiss J, et al. Cutis. 2002;70(2 Suppl):22-9. 3. Tanghetti E, et al. J Drugs Dermatol. 2007;6(2):144-7.
4. Krawtchenko N, et al. Br J Dermatol. 2007;157(Suppl 2):34-40. 5. ZYCLARA® product monograph, 2012. 6. Hanke CW, et al. J Drugs Dermatol.
2011;10(2):165-70. 7. ALDARA® product monograph, 2012. 8. Lebwohl M, et al. New Engl J Med. 2012;366(11):1010-9. 9. Tschen EH, et al. Br J
Dermatol. 2006;155(6):1262-9. 10. Piacquadio DJ, et al. Arch Dermatol. 2004;140(1):41-6. 11. Pariser DM, et al. J Am Acad Dermatol. 2003;48(2):227-32.
Field-directed Treatments: Local
Skin Reactions
Treatment
Local skin reactions
5-FU1
• Erythema, erosion, crusting, ulceration
• Significant erythema, burning, erosion, crusting, and/or ulceration can
occur during treatment and may require treatment interruption
Imiquimod 3.75%, 5%2,3*
• Erythema, flaking/scaling/dryness, scabbing/crusting
• Intense local skin reactions including erythema, scabbing/crusting, and
erosion/ulceration can occur after a few applications, and may require
treatment interruption
Ingenol mebutate 0.015%*, 0.05%4
• Erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation
• Typically occur within 1 day of treatment initiation and peak in intensity up
to 1 week following completion of treatment
• Usually resolve within 2 weeks on face and scalp and within 4 weeks on
trunk and extremities
Aminolevulinic acid or methyl
aminolevulinate with PDT5,6
 Erythema, edema, crusting
Between-study comparisons are not intended due to differences in patient demographics and other study parameters.
*Indicated for face and scalp only.
1. EFUDEX® product monograph, 2004. 2. ZYCLARA ® product monograph, 2012.
3. ALDARA® product monograph, 2012. 4. PICATO® product monograph, 2013.
5. Levulan Kerastick® product monograph, 2004. 6. METVIX™ product monograph, 2009.
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Examples of LSRs
This LSR comprises erythema,
vesiculation, and mild swelling.
This LSR comprises more pronounced
swelling and erythema.
Field-directed Treatments: Other
Adverse Events
Treatment
Other adverse events
5-FU1,2



Imiquimod 3.75%, 5%3,4*

Application site pain, pruritus, burning, dermatitis, soreness, tenderness,
hyperpigmentation, scarring
Insomnia, stomatitis, suppuration, scaling, swelling, irritability, medicinal taste,
photosensitivity, and lacrimation
Laboratory abnormalities (leukocytosis, thrombocytopenia, toxic granulation,
eosinophilia)


Target site pain, tenderness, bleeding, itching, stinging, burning, tingling, irritation,
photosensitivity
Flu-like symptoms, including malaise, fever, nausea, myalgias, and chills
Exacerbation of inflammatory skin conditions
Ingenol mebutate 0.015%*, 0.05%5




Administration site pruritus, irritation, pain, infection
Periorbital pain
Headache
Eyelid edema
Aminolevulinic acid or methyl
aminolevulinate with PDT 6,7


Stinging and burning during light therapy
Application site itching, photosensitivity
Between-study comparisons are not intended due to differences in patient demographics and other study parameters.
*Indicated for face and scalp only.
1. EFUDEX® product monograph, 2004. 2. Cheigh NH. In: DiPiro JT, et al., eds. Pharmacotherapy: A Pathophysiologic Approach. 2008:1584-5.
3. ZYCLARA® product monograph, 2012. 4. ALDARA ® product monograph, 2012. 5. PICATO® product monograph, 2013.
6. Levulan Kerastick® product monograph, 2004. 7. METVIX™ product monograph, 2009.
Counselling Tips for Topical
AK Therapies
• Wash hands before and after
applying treatment
• Use care if applying the medication
near the eyes, nostrils, or mouth
• Some local skin reactions may
become visible and/or cause
discomfort
EFUDEX® product monograph, 2004. ZYCLARA ® product monograph, 2012.
ALDARA® product monograph, 2012. PICATO® product monograph, 2013.
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Patient Counselling Tips: Ingenol
Mebutate
• Apply gel gently with the fingertip to the
treatment area
• Allow to dry for 15 minutes
• Avoid washing or touching the treated skin for 6
hours
• Avoid applying immediately after taking a
shower or less than 2 hours before bedtime
• Do not cover the treated area with a bandage or
other type of dressing
• If a local skin reaction does not improve, contact
the office
• Put medication in a refrigerator (2°C to 8°C) as
soon as possible after picking it up from the
pharmacy and always store it in the fridge
PICATO® product monograph, 2013.
Successful counseling of igenol
mebutate
71
• Ask if physician provided specific
application instructions
• Apply 3 days in a row (2 days for off
face)
• While each tube is listed for 25cm2
each tube is overfilled by 100%, so
actually can get 50cm2
• Therefore, one tube can treat ½ face
• May need to use pliers to squeeze
tube completely empty OR cut tube
with small scissors
• Use small “dots”
Summary
• Actinic keratoses are pre-cancerous skin lesions
that may progress to SCC; progression is
unpredictable
• Risk factors for development of AK lesions
include:
◦
◦
◦
◦
◦
Amount of cumulative/prolonged exposure to UV
Fair skin
Light-coloured hair/eyes
Older age
Male gender
• AK lesions may be visible or non-visible/nonpalpable
• Effective treatment of AK lesions may help to
prevent recurrence and/or progression to SCC
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08/05/2014
Summary
• When there is a significant number of
AK lesions in one area, consider fielddirected therapies to help ensure
adequate treatment of both visible
and non-visible lesions
• Set treatment expectations with
patients, including potential for
adverse effects/local skin reactions
• Follow-up/monitor patients for
recurrence or malignant
transformation
25

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