Canadian Humira Post Marketing Observational Epidemiological Study: Assessing Effectiveness in Psoriasis
Conditions: Psoriasis
Sponsor: AbbVie (prior sponsor, Abbott)

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1.0
Title Page
AbbVie Corporation (AbbVie) 
CLINICAL STUDY PROTOCOL (P12 – 678)
Amendment 2: Canadian Humira Post Marketing 
Observational Epidemiological Study: Assessing 
Effectiveness in Psoriasis (Complete - Psoriasis)
Product Name:
Adalimumab (Humira)
Type of Study:
Observational Study
Date:
August 8th, 2013
CRO(s): 
Cato Research
9900 Blvd Cavendish, suite 400 
Montreal, Quebec
H4M 2V2
Phone (514) 856 2286
Sponsor:
AbbVie Corporation, Limited.
8401
Trans-Canada Highway
Montreal, Qc H4S 1Z1
Medical Writer:
This study will be conducted in compliance with this protocol. 
Confidential Information.
No use or disclosure outside AbbVie
is permitted without prior written 
authorization from AbbVie.
NCT01387815

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2.0
Table of Contents
1.0
Title Page..................................................................................................1
2.0
Table of Contents.....................................................................................2
3.0
Introduction .............................................................................................4
4.0
Rationale.................................................................................................10
5.0
Study Objectives ....................................................................................13
5.1 
Primary Objective:....................................................................... 13
5.2 
Secondary Objectives: ................................................................ 13
5.3 
Study Endpoints.......................................................................... 14
5.3.1 
Primary Endpoint ........................................................................ 14
5.3.2 
Secondary Endpoints:................................................................. 15
6.0
Investigational Plan...............................................................................18
6.1 
Selection of Study Population ..................................................... 19
6.1.1 
Inclusion Criteria ......................................................................... 20
6.1.2 
Exclusion Criteria........................................................................ 21
6.2 
Number of Patients to be Enrolled .............................................. 21
6.3 
Investigator Selection Criteria ..................................................... 22
6.4 
Study Duration ............................................................................ 22
6.5 
Study Conduct ............................................................................ 22
6.5.1 
Description of Activities............................................................... 26
6.5.2 
Product Supply:........................................................................... 29
7.0
Adverse Events.......................................................................................30
7.1 
Adverse Event Definition and Serious Adverse Event 
Categories................................................................................... 30
7.2 
Severity....................................................................................... 32

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7.3 
Relationship to Pharmaceutical Product ..................................... 32
7.4 
Serious Adverse Event Collection Period ................................... 33
7.5 
Serious Adverse Event Reporting............................................... 33
7.6 
Pregnancy Reporting .................................................................. 34
7.7 
Unusual Failure in Efficacy.......................................................... 34
8.0
Ethics and Quality.................................................................................34
9.0
Case Report Forms................................................................................37
10.0
Data Analysis Plan.................................................................................38
10.1 
Overview:.................................................................................... 38
10.2 
General Considerations: ............................................................. 39
10.3 
Sample Size Calculations ........................................................... 41
11.0
Final Report and Publications..............................................................42
12.0
References ..............................................................................................43
List of Tables
Table 1: Study Data Variables Collected by Visit.......................................................25
List of Appendices
Appendix A.  List of Abbreviations and Definition of Terms.............................. 47

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3.0
Introduction 
Psoriasis is an autoimmune illness characterized by chronic non-contagious skin 
manifestations1 caused by an immunologically accelerated cell turnover2. The result is an 
abnormal accumulation of cells to the skin surface2 causing inflammation, thickening, 
scaling, pruritic changes and pain that could extend to the surrounding joints3.
There are five types of psoriasis depending on the symptoms and severity. The most 
common type of psoriasis (approximately 80%) is “plaque psoriasis” where raised and 
inflamed red lesions covered by silver-white scales develop.
The causes of psoriasis are somewhat unknown; however it is believed that genetics and 
the immune system are involved. It is postulated that 10% of the population has a gene 
that predisposes them to psoriasis; however, only 2% of the worldwide population 
develops the illness. The currently held belief is that a multifactorial genetic 
predisposition and an environmental trigger are required for the disease to manifest. 
Potential triggers include stress, an injury to the skin and certain medications such as 
lithium, antimalarials, Inderal, quinidine and indomethacin. Injury induced psoriasis is 
known as the Koebner phenomenon.5 There are certain triggers that could cause specific 
types of psoriasis. For instance, upper respiratory infections, streptococcal throat 
infections, tonsillitis, beta-blockers as well as the three triggers mentioned above can 
cause guttate psoriasis. Appreciation of the different types of Psoriasis and related 
environmental triggers becomes important in studying regional variations in the 
epidemiology and risk factors of the disease.
On the cellular level, the causes of psoriasis begin with T-cells, which have been shown to 
be involved in the development of psoriasis, more specifically Th1 and Th17 cells. When 
the cytokine IL-12 is produced, Th1 cells differentiate which subsequently secrete TNF-Į
and IFN-ɲ. These two cytokines cause vasodilatation, leukocyte migration, activation of 
keratinocytes and, later on, the activation of dendritic cells. The latter effect will begin a 

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cycle of inflammation. Th17 cells are also involved. After they are activated by IL-1, IL-6
and TGF-ɲ, they produce IL-17 and IL-22 which also stimulate keratinocyte activation and 
proliferation. Clearly, the overstimulation of the keratinocytes is the main cause of the 
acceleration of the skin cell growth cycle mentioned earlier.1 Understanding of the 
underlying disease process is essential in defining treatment targets.
Psoriasis affects approximately 125 million people worldwide, which consist of 2-3% of 
the total population.6 In Canada it is estimated that more than 1 million individuals, have 
psoriasis. The prevalence of the disease is 0.8-1%.7 However, these statistics vary 
according to race, ethnic background, region, age and gender
Psoriasis has a major impact on the patient’s quality of life with approximately 60% of 
the patients considering the illness to greatly impact their life.8 However, in Canada, 
according to a study by Lynde et al., 35% of the patients with psoriasis considered the 
disease to be a substantial problem in their daily life. In the same study, 54% of patients 
had lesions on more than 3% of their body.9 Furthermore, psoriasis has a greater negative 
impact in women and younger patients.6 Although not typically considered a severe or 
life threatening condition, in its severe form, affecting more than 10% of the body, life 
expectancy may be decreased for as much as 50% when comparing mild to severe 
psoriasis 6, 10
The typical first line of treatment for early mild psoriasis is topical medications. These 
include creams, ointments and shampoos11 that slow down or normalize the accelerated 
growth cycle of the skin cells and hence reduce the inflammation.12 Corticosteroid 
ointments are generally the first line topical treatment of choice and are effective in 
reducing the swelling and the redness of the lesions.13 Corticosteroids provide 
symptomatic relief but may not cure the disease and may even cause exacerbation with 
high dose or prolonged use. Topical corticosteroids are associated with possible side 
effects resulting in skin damage, such as skin thinning, changes in pigmentation, easy 
bruising, stretch marks, redness and dilated blood vessels on the surface. Furthermore, if 

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applied on, in or near the eye, cataracts and glaucoma may occur. 13
There are some topical drugs that do not contain corticosteroids, like Dovonex 
(calcipotriene), and Vertical (calcitriol). Dovonex and Taclonex (calcipotriene and 
betamethasone dipropionate) have some non-severe side effects, the most common being 
skin irritation, stinging and burning for Dovonex and itching, rash, skin thinning and 
burning for Taclonex.14 Furthermore, the patient has an increased risk of skin tumors 
because of the sensitivity to light. Some antipsoriatic topical drugs contain retinoids, such 
as Tazorac (tazarotene). These medications act less rapidly than corticosteroids, but have 
fewer adverse effects.3,14 Other topical medications for psoriasis include Zithranol-RR 
(Anthralin), vitamin D3 or A, coal tar and salicylic acid.3,12 Anthralin has no long-term 
side effects, though it may cause skin irritation and may stain light-colored hair and 
unaffected skin.14
For moderate or severe psoriasis, affecting more than 3% of the body surface area, topical 
treatments are generally not effective and more aggressive therapy is required.11
Phototherapy is an effective second line treatment for moderate psoriasis or mild disease 
that has not responded to topical therapy. Phototherapy consists of regularly exposing the 
skin to ultraviolet (UV) light which reduces inflammation by reducing T-cell 
proliferation.3 Ultraviolet light treatment is classified as UVA and UVB. UVA light is the  
principle component of sunlight and it is used in combination with photosensitizing 
medications such as psoralen when it is referred  to as  PUVA. The disadvantages of UVA
and PUVA treatments include a high risk of cancer along with immediate reactions 
including, nausea, headache, burning of the skin and photosensitivity. Use of topical 
PUVA or baths have been proven to be a safer and effective alternative. 22-23
UVB treatment is based on another component of sunlight and it is available as broadband 
or narrowband therapy. Broad band UVB phototherapy uses light with a wavelength range 
between 290 and 350 nanometers. UVB treatment is less carcinogenic when compared to 
UVA and does not require co administration of medications. However, it may be less 

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effective. Narrowband UVB uses light in the 311-313 nanometer wavelength range. It is 
highly effective and does not require the use of photosensitizing medications.22-23
Compliance with treatment is essential for success of phototherapy. This treatment is 
most recommended when the patient has plaque psoriasis, guttate psoriasis or psoriasis 
on the palms and soles.15 However, if employed over a long period of time, it is 
associated with an increase of risk of skin cancers. Recently two new phototherapy 
treatments have been by the FDA for mild to moderate psoriasis: the excimer and pulsed 
dye laser which better control the beam of light (UVB) to specifically target the affected 
skin area.3, 15
For moderate to severe psoriasis that does not respond to topical agents or phototherapy, 
systemic treatments are used3. These include traditional and biologic disease modifying 
agents. Methotrexate and cyclosporine are traditional systemic disease modifying agents 
that have been proven to be efficacious in the management of    psoriasis16. Cyclosporine 
binds to dihydrofolate reductase leading to the inhibition of synthesis of DNA, RNA,
thymidylates and proteins and thus reducing the skin proliferation. Adverse effects 
associated with methotrexate include liver damage reduced leukocytes, infections and 
malignancies.17
Cyclosporine suppresses the immune system and prevents skin cell proliferation. While 
efficacious in controlling the symptoms of psoriasis, cyclosporine has an increased risk 
for serious adverse events and prolonged use or use by patients with chronic conditions or 
compromised immune systems is not recommended. Among the side effects of 
cyclosporine the most important are decreased kidney function, headache, hypertension, 
elevated cholesterol, excessive hair growth, tingling or burning sensation in arms and/or 
legs, skin sensitivity, increased growth of gum tissues, influenza-like symptoms, upset 
stomach, tiredness and muscle, bone or joint pain. Also, if the drug is taken over a long 
period of time, the patient could develop skin cancer or kidney damage. This risk 
increases with a longer exposure.18

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Biologic systemic agents and specifically anti-TNF-ĮLQKLELWRUVKDYHEHHQGHYHORSHGLQ
recent years and have been proven efficacious in the management of patients. As 
mentioned earlier, TNF-ĮDF\WRNLQHFDXVHVWKHSUROLIHUDWLRQRINHUDWLQRF\WHVWKURXJK
the mediation of inflammatory Th1 cells (CD4 T-cells) that bind to MHC (major 
histocompatility complex) class II molecules and present an antigen to the T-cells. Some 
of these cytokines, including TNF-Į VWLPXODWH WKH DFtivation of macrophages which 
cause inflammation and induce vascular permeability, leukocyte migration and the 
formation of new vessel networks. TNF is over expressed in psoriatic plaques and TNF-
induced proteins are found in psoriatic lesions but not in healthy areas. This would 
suggest that TNF is involved in the pathogenesis of the disease by increasing the 
inflammatory process and augmenting the proliferation of keratinocytes in the affected 
regions. It is also postulated that TNF increases cellular adhesion, activation and 
promotion of angiogenesis. Therefore, agents that block the activity of TNF-ĮKDYHEHHQ
proven to treat psoriasis and reduce inflammation.19
Adalimumab (Humira®) is a fully human anti-TNF-Į PRQRFORQDO DQWLERG\ that is an 
analogue to human IgG1. It attaches to TNF and prevents its binding to p55 and p75 TNF 
receptors on the cell surface. It is currently approved for the treatment of psoriasis, 
juvenile and adult rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and 
Crohn’s disease. Currently dosing in patients with moderate to severe psoriasis involves 
an initial dose of 80mg subcutaneously, followed by a 40mg injection every second week 
beginning one week after the initial 80mg dose.
Due to their immune suppression properties, anti-TNF alpha agents including 
adalimumab may be associated with increased risk for serious infections including 
tuberculosis, candidiasis, listeriosis, pneumocystis, pneumonia, pyelonephritis, septic 
arthritis and septicemia. Patients may also be at risk for serious opportunistic infections. 
However, these events have been predominantly reported in patients with compromised 
immune systems. Some non-severe adverse effects are a moderately painful injection 

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site20 including redness, itching, bruising, pain or swelling, stomach pain, nausea, 
headache and back pain.21 Rare side effects include malignancies, reversible lupus 
(without renal or CNS complications) and cytopenias. Therefore all patients treated with 
anti-TNF alpha agents must be monitored for serious infections and particularly 
tuberculosis before, during and after treatment. In addition monitoring of liver function,
CBC and hepatitis profile are recommended.20
The efficacy of adalimumab in controlling the symptoms of psoriasis has been 
demonstrated in several controlled clinical trials. Taken collectively the results of these 
studies that have been conducted on over 1600 patients with moderate to severe chronic 
plaque psoriasis who were candidates for systemic therapy or phototherapy have shown 
that adalimumab is efficacious in controlling the symptoms of psoriasis and in improving 
the quality of life of patients. More specifically, when compared to placebo or 
methotrexate, patients treated with adalimumab had a significantly higher therapeutic 
response rate, defined as achieving a PASI 75 and a Physician Global Assessment (PGA)
YDOXHRILQGLFDWLQJFOHDURUPLQLPDOGLVHDVHDWZHHNV7KHPDJQLWXGHRIHIIHFW
versus placebo ranges from four-fold (79.6% versus 18.9%) to ten-fold (70.9% versus 
6.5%) for PASI 75 and from 2.5 times (73.1% versus 30%) to 14.5 times (62.2% versus 
4.3%) for PGA of clear or minimal. When compared to methotrexate the magnitude of 
effect is 2.2 times for PASI 75 (79.6% versus 35.5%) and 2.5 times for PGA of “clear or 
minimal” (73.1% versus 30%) 1,11-18,22-29. In addition, in one clinical trial patients crossed 
over to placebo after 33 weeks of treatment with adalimumab were significantly more 
likely to lose therapeutic response when compared to patients that were maintained on 
adalimumab up to week 52. With respect to quality of life, when compared to patients 
treated with placebo or methotrexate those treated with adalimumab in these controlled 
clinical trials have had better improvement in the Dermatology Quality of Life Index 
(DLQI) total score as well as in the disease severity, pain and pruritus subscales. Better 
improvement in the Physical and Mental subscales of the Medical Outcomes Study Short 
Form 12 (SF-12) was also observed for the adalimumab treated patients when compared 

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to placebo. 
In Canada, the Canadian Expert Drug Advisory Committee (CEDAC) of the Canadian 
Agency for Drugs and Technologies in Health has recommended adalimumab in the 
treatment of psoriasis under the following conditions:
i.
Patient is diagnosed with severe debilitating psoriasis; and
ii.
Body surface involvement of more than 10% and / or significant involvement of 
the face, hands, feet or genital areas; and
iii.
Failure to respond to, contraindication or intolerance to methotrexate and 
cyclosporine; and
iv.
Failure to respond to, intolerant to or unable to access phototherapy. 
4.0
Rationale
Complete is a three part Canadian observational research study program aimed at 
assessing the real life effectiveness of adalimumab in the management of Psoriasis, 
Psoriatic Arthritis and Ankylosing Spondylitis. The general aim of the program will be to 
identify and describe common elements in these three conditions with respect to the 
population at risk, comorbidities, burden of illness, prognostic factors and response to 
treatment in the real – life setting. This will have significant implications for educating 
physicians and patients in the assessment and identification of signs and symptoms that 
would prompt further investigation and possible earlier diagnosis and treatment of these 
conditions. The results will also have an important impact on the advancement of our 
understanding of the causal pathways for these conditions that could eventually lead to 
improved patient management. Therefore, in addition to addressing the objectives of the 
individual studies, the data obtained in the program will also be used to address this 

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general aim. 
With respect to Psoriasis, adalimumab has been approved in Canada for patients with 
moderate to severe Psoriasis that are candidates for systemic therapy. For patients with 
moderate plaque Psoriasis adalimumab should be used for after phototherapy has been 
ineffective or inappropriate (Canadian Product Monograph). To date real – life 
observational data allowing the comparison of the effectiveness of adalimumab to topical 
agents and traditional systemic agents in patients failing current treatment have not been 
reported. There is also currently a knowledge gap with respect to the practice patterns and 
regional variation in the approach used by Canadian physicians in the management of 
patients with psoriasis. 
Psoriasis presents a significant burden of illness through the physical and emotional 
manifestations that significantly affect the patient’s quality of life as well as loss of 
productivity and direct and indirect costs. Assessment of the impact of different 
approaches to the management of moderate to severe psoriasis on these patient centric 
outcomes is therefore of paramount importance. Given that patient reported outcomes 
have a cultural and regional influence, the assessment of these outcomes in specific 
regions is also of high relevance and importance in the assessments of regional and global 
benefit – risk ratios.
An important consideration of Psoriasis is the fact that approximately 30% of the patients 
develop psoriatic arthritis (PsA). To date, there are no known predictors of progression to 
PsA among patients with psoriasis. In addition, it is known that triggers of psoriasis flare -
ups and disease progression have an environmental and genetic determinant. There is 
currently a knowledge and patient management gap with respect to the screening and 
detection of flare – up triggers or articular and extra articular signs and manifestations 
indicating progression of psoriasis or onset of PsA. There is therefore a general need for 
the assessment of these questions. However, given the potential genetic and 
environmental effect on the incidence of Psoriasis as well as it severity and progression, 

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these questions must be addressed at the regional level.
Finally, continuous monitoring of the safety of adalimumab is essential in order to assess 
whether the safety profile in a real – life setting is comparable to that expected on the 
basis of the data reported in controlled clinical trials and to ensure detection of any 
emerging signal. 
The current study will address the above questions by conducting a prospective 
observational study of Canadian patients with moderate to severe psoriasis for whom 
change of current treatment is indicated. Patients will enter the cohort at the time that 
their treatment is changed and therefore patients treated with topical agents, traditional 
systemic agents and adalimumab will be eligible to be included in the study. The 
rationale for limiting the anti-TNF alpha agent to adalimumab is based on the prevention 
of within class variation with respect to clinical decision making, response to treatment 
and incidence of adverse events. 
Follow up will be for 24 months and assessments will be as per routine clinical care and 
according to the judgment of the treating physician. However, follow up visits at 
approximately 3, 6, 12, 18 and 24 months will be recommended. 
There will be a total of 660 patients with psoriasis enrolled from the clinics of 30 – 40 
Canadian community dermatologists. The sample of clinicians will be a random 
proportional representation of the distribution of dermatologists and patients in Canada, 
thus allowing valid generalization to the Canadian population of psoriasis patients. In 
addition, enrollment of the patients in the study will be on the basis of change in current 
treatment due to lack of response or tolerability. The decision to change treatment must 
be reached prior to enrollment in and independently of the current study. 
The study will assess clinical and patient reported outcomes that are relevant in the 
management of psoriasis and its impact on the patient’s quality of life and societal burden 

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of illness. The design is that of a prospective observational study with its inherent biases 
including confounding by indication. Statistical methods including multi-variate models 
and propensity scores will be used to adjust between group differences with respect to 
prognostic baseline characteristics. Mixed effects models will be incorporated to 
compensate for unequal follow up and lack of precisely scheduled visits. The design and 
statistical analysis employed are therefore required and appropriate to produce a valid 
real – life assessment and comparison of the different modes for the management of 
psoriasis that are currently used in Canada. 
5.0
Study Objectives
5.1
Primary Objective:
To compare the real – life effectiveness of adalimumab to topical and traditional systemic 
agents in the management moderate to severe Plaque PS.
5.2
Secondary Objectives:
i.
To compare the real – life effectiveness of adalimumab to topical and traditional 
systemic agents in the prevention of development of articular and extra-articular 
manifestations in patients with moderate to severe Plaque PS.
ii.
To describe the profile and regional variation in terms of demographics, disease 
parameters, flare – up trigger, comorbidities and concomitant medication use of 
Canadian patients with moderate to severe Plaque PS.
iii.
To describe the current practices and regional variation among Canadian 
dermatologists with respect to the screening and detection of articular 
manifestations indicating onset of PsA in patients with moderate to severe Plaque 
PS.

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iv.
To describe the incidence of and risk factors for the development of   articular and 
extra-articular manifestations in Canadian patients with moderate to severe Plaque 
PS.
v.
To describe the current population based burden of illness incorporating Health 
Care Utilization, Health Care Costs, Quality of Life, Psychological impact Work 
Productivity of moderate to severe Plaque PS in Canada.
vi.
To assess the impact of topical agents, traditional systemic agents and 
adalimumab on the Plaque PS related burden of illness incorporating Health Care 
Utilization, Health Care Costs, Quality of Life, Psychological impactWork 
Productivity in Canada.
vii.
To provide an ongoing assessment of the safety and tolerability of adalimumab, 
systemic and topical agents used in the management of moderate to severe Plaque 
PS in Canada.
5.3
Study Endpoints
5.3.1
Primary Endpoint
The primary effectiveness outcome measure for the current study will be the physician 
global assessment (PGA) of “0” or “1” indicating clear or minimal disease according to 
the following classification:
Score
Category
Description
0
Clear
Plaque elevation = 0 (no elevation over normal skin)
Scaling = 0 (no scale)
Erythema = ± (hyper pigmentation, pigmented macules, diffuse 
faint pink or red coloration)
1
Minimal
Plaque elevation = ± (possible but difficult to ascertain whether 
there is a  slight elevation above normal skin)
Scaling = ± (surface dryness with some white coloration)
Erythema = up to moderate (up to definite red coloration)

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Score
Category
Description
2
Mild
Plaque elevation = slight (slight but definite elevation, typically 
edges are indistinct or sloped)
Scaling = fine (fine scale partially or mostly covering lesions)
Erythema = up to moderate (up to definite red coloration)
3
Moderate
Plaque elevation = moderate (moderate elevation with rough or 
sloped edges)
Scaling = coarser (coarse scale covering most of all of the lesions)
Erythema = moderate (definite red coloration)
4
Severe
Plaque elevation = marked (marked elevation typically with hard or 
sharp edges)
Scaling = coarse (coarse, non tenacious scale predominates 
covering most or all of the lesions)
Erythema = severe (very bright red coloration)
5
Very 
severe
Plaque elevation = very marked (very marked elevation typically 
with hard sharp edges)
Scaling = very coarse (coarse, thick tenacious scale over most of all 
of the lesions; rough surface)
Erythema = very severe (extreme red coloration; dusky to deep red 
coloration)
The primary outcome measure will be the percent of patients with PGA VFRUHRIDW
months of treatment. 
5.3.2
Secondary Endpoints:
The following secondary endpoints will be assessed:
i.
Time to achieving PGA RYHUPRQWKVRIIROORZXS
ii.
Percent of patients with PGA DWDQGPRQWKV
iii.
Signs and symptoms suggesting onset of PsA:
i.
Change in the modified Psoriasis and Arthritis Screening Questionnaire 
(PASQ). This is an 11 item tool that ascertains self reported presence of 
joint pain and swelling. This will be assessed at 3, 6, 12, 18 and 24 

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months.
iv.
Change in Body Surface Area (BSA) of psoriasis involvement at 6, 12, 18 and 24 
months. The BSA is an indicator of disease severity and the affected area is 
expressed as a percentage of the total body surface area.  
v.
Change in Patient Global Assessment of Disease Activity based on a six point 
Likert Scale at 3, 6, 12, 18 and 24 months.
vi.
Change in the Dermatology Quality of Life Index (DLQI) at 3, 6, 12, 18 and 24 
months. The DLQI is a self administered questionnaire comprised of 10 items 
assessing a patient’s skin and problems associated with skin disease. The 10 
questions in the DLQI converge into six domains that measure symptoms and 
feelings, daily activities, leisure, work and / or school, personal relationships and 
satisfaction with treatment.
i.
Proportion of patients achieving and time to DLQI   WKURXJK WKH 
months of treatment.
vii.
Change in Beck Depression Inventory at  6, 12 and 24 months: This will be used 
to assess the presence and severity of depression. It consists of 21 items 
converging to two scales measuring somatic and affective components of 
depression. The questions assess hopelessness and irritability, cognition such as 
guilt or feelings of being punished, as well as physical symptoms such as fatigue, 
weight loss and loss of interest in sex. Given the important emotional and social 
impact of psoriasis assessing psychological impairment is important in order to 
fully appreciate the impact of the disease and effect of treatment on the patient’s 
life.
viii.
Change in Medical Outcomes Study Short Form 12 (SF-12) at 6, 12 and 24 
months. The SF-12 Health is a 12-item general health self administered 

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questionnaire consisting of 8 scales measuring Physical Function, Physical Role 
limitations, Vitality, General Health,  Pain, Social Function, Emotional Role 
limitations, and Mental Health.
ix.
Change in Work Limitation Questionnaire at 6, 12 and 24 months. The WLQ is a 
self-administered questionnaire comprised of 25 questions. It assesses the degree 
to which the patient’s work is affected due to health problems or health-related 
productivity loss. The 25 questions are further divided into four scales: time 
management, physical demands, mental-interpersonal demands and output 
demands. The scoring for the WLQ ranges from 0 (none of the time) to 100 (all of 
the time) and represent the portion of time in the prior two weeks that those 
answering the questionnaire were limited in their abilities while at work. 
Furthermore, an algorithm is present that can convert scores obtained using the 
WLQ into an estimate of productivity loss. Considering the important effect of
psoriasis on the patient’s ability to deal with the emotional and physical demands 
of employment, the assessment of the impact of disease and treatment on work 
related productivity loss is highly relevant. 
x.
Health Care Utilization Questionnaire through the 24 months of treatment. This 
will be a descriptive self administered series of questions aimed at measuring the 
patient’s health care utilization and economic impact of the disease. More 
specifically the questionnaire will ascertain the frequency of physician visits, 
utilization of other health care professionals, visits to clinics, emergency rooms 
and hospitalizations that are related to psoriasis. In addition, use of prescription 
and non–prescription medications for the management of psoriasis will be 
determined. Out of packet expenses for medications and health care will be 
assessed. The patient’s occupation and household income range will be used as a 
proxy to socioeconomic status.
xi.
Compliance with treatment will be assessed through the 24 months of treatment 

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by self report of missed topical applications, medication doses or adalimumab 
injections.
xii.
Change in medical history and concomitant medication use through the 24 months 
of treatment will be recorded assessed by the treating physician as per routine 
care.
xiii.
Use and frequency change of phototherapy for psoriasis through the 24 months of 
treatment will be ascertained by a targeted question in the patient assessment.
6.0
Investigational Plan
This is a Canadian Post Marketing Observational Study utilizing a prospective cohort 
design. Patients are entered into the study cohort at the time of change of their Psoriasis 
treatment for any reason and are followed for a maximum of 24 months with 
recommended assessments at 3, 6, 12, 18 and 24 months after baseline. Treatment of the 
patients and follow up will be according to the physician’s judgment, regional regulations 
and the product monograph. Off-label use will not be permitted and these patients will 
not be included in the study. Dose changes including escalation will be allowed as per the 
physician’s judgment for patients that were treated as per indication when they were 
enrolled in the study. 
There will be 660 patients enrolled from the practices of approximately 30 – 40 
dermatologists across Canada. The study sample will be randomly selected and 
proportional to the Canadian population and distribution of dermatologists in Canada. 
The following patient cohorts will be defined:
i.
Initiated treatment with a new topical agent that was not used before or already on 
treatment with a topical agent and not responding requiring a change of treatment 

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type, frequency or dose.
ii.
Initiated treatment with a new systemic agent that was not used before alone or in 
combination with topical agents.
iii.
Initiated on treatment with adalimumab alone or in combination with topical 
agents.
In the case that the patient is switched from one cohort to another during the course of the 
study, follow up will continue as per the study protocol. For these cases, the treatment 
will be considered as a time dependent variable in the assessment of the study outcomes. 
In addition, depending on the number of patients switching cohorts, separate cohorts may 
be defined to include those patients that change treatment during the study.  
Effectiveness outcome measures will include changes in clinical outcomes and quality of 
life. Health economic assessments will be conducted to determine the impact of treatment 
on Psoriasis related burden of illness. The impact of Psoriasis and different treatments on 
work productivity will be assessed. The study will also identify prognostic factors for 
progression to Psoriatic Arthritis and treatment gaps in the detection and screening for 
articular and extra-articular manifestations. Regional differences within Canada with 
respect to the patient profile and the management of patients with Psoriasis will be 
described.  
6.1
Selection of Study Population 
Patients will be enrolled from the offices of community dermatologists across Canada 
treating patients with Psoriasis. The sample of physicians invited to participate in the 
study will be selected in a way that it is a random representative sample of the Canadian 
population and distribution of dermatologists. 
All patients with psoriasis treated at the participating centers will be potentially eligible 

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to be included in the study. Those fulfilling the study inclusion and exclusion criteria will 
be invited to participate in the study by the site investigator or designee. Treatment will 
be according to the treating physician’s judgment and routine care and must adhere to the 
product monograph and regional regulatory requirements. Use of medications for the 
management of psoriasis that is off–label or not in accordance with existing regulations 
will not be permitted. Prior to inclusion in the study all patients will be required to sign a 
written informed consent agreeing to allow use of their data in the study. Since this is not 
an interventional study and patients are treated as per routine care the purpose of the 
informed consent will be to allow the use of the data and contact of the patients by the 
study personnel as required. The study protocol, informed consent, questionnaires and 
participating physicians will be approved by a central or local independent ethics review 
board as required by regional or institutional regulations. 
Changing the patient’s treatment including initiation of treatment with adalimumab must 
be exclusively the treating physician’s decision and must be reached prior to patient 
screening and enrollment and has to be entirely independent of the conduct of the study. 
The observational nature of the study dictates that all treatments used in the current study, 
including adalimumab, must be prescribed as per routine care and in accordance to the 
Canadian and provincial marketing authorization and criteria.  
6.1.1
Inclusion Criteria
The following inclusion criteria will be applied:
i.
Adult > 18 years old
ii.
Has provided written informed consent allowing the use of their data for the study 
and providing permission for contact by the study personnel.

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iii.
Active moderate or severe Plaque PS according to the judgment of the treating 
physician.
iv.
The treating physician has decided to change the current treatment or add 
additional treatments for any reason including but not limited to inadequate 
response, intolerance, sub-optimal compliance or patient preference.
6.1.2
Exclusion Criteria
The following exclusion criteria will be applied:
i.
Currently participating in another prospective study  with similar objectives. 
ii.
Patient cannot or will not sign informed consent. 
iii.
Presence of other condition that, in the opinion of the treating physician, prohibits 
the patient from participating in the study or obscures the assessment of the 
treatment of Plaque PS.
6.2
Number of Patients to be Enrolled 
A total of 660 patients will be enrolled in the current study from the practices of 30 – 40 
dermatologists. A maximum of 30 patients per site will be allowed. Recruitment will be 
over a 24 month period. In order to provide adequate power to assess the effect of 
different treatment modalities, it will be recommended that 50% of the patients from each 
site will be initiated on treatment with adalimumab. 

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6.3
Investigator Selection Criteria 
i.
A random sample of 30-40 dermatologists will participate in the study.
a.
Physicians participating in the study must have experience in the conduct 
of clinical research and in particular good clinical practices (GCP) or must 
be willing to be trained in GCP.
6.4
Study Duration
All patients will be followed for 24 months. Given the observational nature of the study 
there will be no pre-defined protocol driven assessments and physician visits could take 
place according to the routine practice or the judgment of the treating physician. 
However, assessments at 3, 6, 12, 18 and 24 months after baseline will be recommended 
and encouraged given that this is within the acceptable practice patterns for patients 
undergoing treatment for moderate to severe psoriasis. In certain cases patients may be 
assessed more frequently than what will be recommended. Physicians will be asked to 
record in the Case Report Forms data from all visits occurring during the study period. 
6.5
Study Conduct 
The following sections describe the details regarding the execution of the study. 
This is a multi-center Canadian observational study utilizing a prospective cohort design. 
As an observational study there will be no interventions or interference with the routine 
care of the patient. 
All treatments will be prescribed and utilized as per the judgment of the treating 
physician and in accordance with the product monograph and regional requirements. 
As per the product monograph: “Before initiation, during and after treatment with 
adalimumab patients should be evaluated for active or latent tuberculosis infection with a 

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tuberculin skin test. Treatment of latent tuberculosis infections should be initiated prior to 
therapy with adalimumab. When tuberculin skin testing is performed for latent 
tuberculosis infection, an induration size of 5 mm or greater should be considered 
positive, even if vaccinated previously with Bacille Calmette-Guérin (BCG). The 
possibility of undetected latent tuberculosis should be considered especially in patients 
who have immigrated from or traveled to countries with a high prevalence of tuberculosis 
or who had close contact with a person with active tuberculosis. If latent infection is 
diagnosed, appropriate prophylaxis in accordance with the Canadian Tuberculosis 
Standards and Centers for Disease Control and Prevention guidelines should be instituted. 
Anti-tuberculosis therapy prior to initiating HUMIRA® should also be considered in 
patients who have a negative test for latent tuberculosis but have risk factors for
tuberculosis infection. The decision to initiate antituberculosis therapy in these patients 
should only be made after taking into account both the risk for latent tuberculosis 
infection and the risks of anti-tuberculosis therapy. If necessary, consultation should 
occur with a physician with expertise in the treatment of tuberculosis. Active tuberculosis 
has developed in patients receiving adalimumab whose screening for latent tuberculosis 
infection was negative, and some patients who have previously received treatment for 
latent or active tuberculosis have developed active tuberculosis while being treated with 
TNF-blocking agents. Patients receiving adalimumab should be monitored for signs and 
symptoms of active tuberculosis, particularly because tests for latent tuberculosis 
infection may be falsely negative. The risk of false negative tuberculin skin test results 
should be considered especially in patients who are severely ill or immunocompromised. 
Patients should be instructed to seek medical advice if signs/symptoms (e.g., persistent 
cough, wasting/weight loss, low grade fever) suggestive of a tuberculosis infection occur, 
and physicians should monitor for signs and symptoms of active tuberculosis, including 
patients who are tuberculosis skin test negative” (HUMIRA® Product Monograph).
With respect to the frequency and schedule of assessments, although there are no study 
specific requirements, follow up visits at 3, 6, 12, 18 and 24 months after baseline will be 

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recommended. Data obtained from more frequent visits or visits conducted at other time 
points will also be recorded in the study Case report Form. In fact, in order to avoid any 
bias and loss of information all information regarding the management of the patients 
during the 24 month follow up period of the study should be recorded in the study data 
collection forms. In addition to clinical data that will be ascertained by the treating 
physician, patient reported outcomes will also be ascertained through self administered 
questionnaires.  
The following table describes the data that will be collected and the recommended timing 
of the assessments.

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Table 1: Study Data Variables Collected by Visit
Month
Variable 
0
3
6
12
18
24
Visit Number
1
2
3
4
5
6
Demographics:
Age
X
Gender
X
Employment status
X
Smoking
X
Alcohol use
X
Anthropometric measurements:
Height
X
Weight
X
X
X
X
X
X
Physical Examination
X
X1
X1
X1
X1
X1
Medical History:
Previous Conditions
Current Comorbidity
Family History
X
X1
X1
X1
X1
X1
Psoriasis History
Date of diagnosis
X
Known triggers
X
Frequency and Pattern of  Flare – Ups
X
Family History of Psoriasis
X
Prior Treatment Details:
Dose
Duration
Reason for discontinuation
X
Concomitant Medications (Emphasis on Psoriasis 
Treatment) 
X
X
X
X
X
X
Concomitant Psoriatic Arthritis
X2
Rheumatoid Factor 
X2
C - Reactive Protein or hs-CRP
X2
X2
X2
X2
X2
X2
Erythrocyte Sedimentation Rate (ESR)
X2
X2
X2
X2
X2
X2
Clinical Laboratory Tests
X2
X2
X2
X2
X2
X2

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Month
Variable 
0
3
6
12
18
24
Visit Number
1
2
3
4
5
6
Body Surface Area (BSA)
X
X
X
X
X
Psoriasis and Arthritis Screening Questionnaire 
(PASQ)
X
X
X
X
X
X
Use of Phototherapy 
X
X
X
X
X
X
Physician’s Global Assessment of Disease Activity (6 
Point Likert)
X
X
X
X
X
X
Patient’s Global Assessment of Disease Activity (VAS)
X3
X3
X3
X3
X3
X3
Dermatology Life Quality Index
X3
X3
X3
X3
X3
X3
Medical Outcomes Study – Short Form 12
X3
X3
X3
X3
Health Care Utilization Questionnaire
X3
X3
X3
X3
Beck Depression Inventory
X3
X3
X3
X3
Work Limitations Questionnaire
X3
X3
X3
X3
Rheumatology Consult4
X
X
X
X
X
X
Compliance assessment
X
X
X
X
X
1. Only changes from previous visit will be recorded
2. Only if used as part of routine care. For the baseline visit, historical data up to 6 
months could be used.
3. Self Administered questionnaires. These could be completed at the physician’s 
office, at home and sent by mail.
4. Relevant sections of the Case Report Form to be completed by rheumatologists or 
information must be obtained from the rheumatologists.
6.5.1
Description of Activities
Screening and Baseline Assessments:
Participating physicians will be asked to assess for potential eligibility all sequential 
patients with Psoriasis for whom a change in treatment regimen is being considered.  

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Following an explanation of the study by the physician or designee, a written informed 
consent will be signed by the patients that agree to participate. Subsequent to obtaining 
written informed consent, potential eligible patients will be assessed for inclusion and 
exclusion criteria. Those that qualify will be entered in the study cohort. All baseline 
assessments will be conducted during the baseline / screening visit. The physicians or 
designee will be required to complete all data on the baseline visit section of the Case 
report Form using data ascertained by interview or examination of the patient or review 
of the patient’s chart. 
There are no laboratory examination requirements for the current study beyond those that 
are part of routine care. Historical data of up to six months could be used for the baseline 
values for laboratory tests. 
Follow-Up Assessments (3, 6, 12, 18 and 24 months):
Given the observational nature of the study there no pre-determined protocol defined 
requirements for follow up schedules. Physicians will manage the patients in accordance 
with their current practice, their judgment and regional requirements in the case of 
reimbursement policies. However, investigators will be encouraged to follow the 
recommended schedule of assessments for the patients that are enrolled in the study. In 
addition, all information and data obtained at any visit occurring during the 24 follow up 
period of the study, including those that are outside of the recommended schedule, will be 
recorded in the study Case Report Form. 
Laboratory tests are not required for the purposes of the study. However, when any tests 
are conducted as part of routine care or indicated by the condition of the patient, all 
results should be recorded in the study Case Report Form in physical changes section.
Informed Consent:
Signed written informed consent will be obtained from all patients prior to conducting 
any study activities including eligibility assessments. Informed consent may be obtained 

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from the patient or legally authorized representative. 
Physical Examination and Medical History:
During the baseline assessment the results of a complete physical examination and 
medical history will be recorded in the study Case Report Form. For subsequent follow 
up assessments, only clinically important changes in the Medical History and Physical 
Examination will be recorded. 
Prior and Concomitant Therapy:
Details of any treatment whether prescription or over the counter used for Psoriasis 
before and during the study will be recorded in the Case Report Form. These will include 
dose, frequency and duration of treatment and route.
Compliance:
Compliance with the treatment for Psoriasis will be ascertained by a self administered 
questionnaire and interview by the treating physician. 
Self Administered Questionnaires:
Patients will be informed about the study requirements with respect to the completion of 
the self administered questionnaires and will be asked to complete the baseline set of 
questionnaires while at the physician’s office. This will allow the patients to ask any 
questions and obtain guidance on how the questionnaires are to be completed. Patients 
will complete the questionnaires and mail them to the data management center, or  return 
them to the treating physicians. During the baseline assessments, patients will be asked to 
indicate the methods by which they wish to be contacted by the study personnel. The 
options will be telephone, mail or e-mail. As part of the written informed consent patients 
will be asked to explicitly agree to be contacted using these methods for the purposes of 
the study and will be asked to provide their contact coordinates.
Patients will be identified only through the randomly generated study patient ID number. 

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Any identifying information will never be included on any questionnaire. If the patient 
chooses to mail-in or complete the questionnaire at the investigator sites, the return 
envelop will include only the patient ID and no other identifying data. Only the study 
coordinators will have access to patient information that will be use to follow up for non-
responders.
Physician and Patient Recruitment and Retention:
Given the observational nature of the study one of the most important challenges will be 
patient retention and minimization of loss to follow up. The project manager will monitor 
patient follow up in the study.  
Patient Discontinuation from the Study:
Patients could be withdrawn from the study at any time by the treating physician or on 
their own accord. Patients that participate in another trial will be withdrawn from the 
study. Patients that terminate treatment or switch from their current treatment will be 
followed for the 24 month study follow up period. Patients may change treatment at the 
discretion of the physician including switching from one of the defined treatment cohorts 
to another. Lack of therapeutic response, low compliance to treatment or the incidence of 
adverse events will not necessitate study withdrawal. 
6.5.2
Product Supply:
In the current study patients will be treated with topical agents, traditional systemic 
agents and adalimumab as monotherapy or in combination.  As an observational study all 
treatments will be accessed as per routine customary practice in the region. More 
specifically, AbbVieE will not supply or reimburse for any treatment used by the patients 
in the study. Patients will be prescribed the medications by the treating physician and will 
acquire these through the available insurance plan / government reimbursement or 
purchase with their own funds. All medications will be used in accordance to the current 
marketing label, the product monograph and regional requirements. 

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7.0
Adverse Events
The primary aim of the current PMOS is to assess real life effectiveness. Given that the 
primary objective is not to assess any safety parameters only spontaneously reported 
Serious Adverse Events (SAEs), unusual failure in efficacy and Pregnancies must be 
reported. 
7.1
Adverse Event Definition and Serious Adverse Event 
Categories
An adverse event (AE) is defined as any untoward medical occurrence in a patient, which 
does not necessarily have a causal relationship with their treatment. An adverse event can 
therefore be any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of a medicinal product, 
whether or not the event is considered causally related to the use of the product.
Such an event can result from use of the drug as stipulated in the labeling, as well as from 
accidental or intentional overdose, drug abuse, or drug withdrawal. Any worsening of a 
pre-existing condition or illness is considered an adverse event.
If an adverse event meets any of the following criteria, it is considered a serious adverse 
event (SAE):
Death of Subject An event that results in the death of a subject.  
Life-Threatening An event that, in the opinion of the investigator, would have resulted 
in immediate fatality if medical intervention had not been taken. This does not include an 
event that would have been fatal if it had occurred in a more severe form.  
Hospitalization An event that results in an admission to the hospital for any length of 

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time. This does not include an emergency room visit or admission to an outpatient 
facility.  
Prolongation of Hospitalization An event that occurs while the study subject is 
hospitalized and prolongs the subject's hospital stay.  
Congenital Anomaly An anomaly detected at or after birth or any anomaly those results 
in fetal loss.  
Persistent or Significant Disability/Incapacity An event that results in a condition that 
substantially interferes with the activities of daily living of a study subject.  Disability is 
not intended to include experiences of relatively minor medical significance such as 
headache, nausea, vomiting, diarrhea, influenza and accidental trauma (e.g., sprained 
ankle).
Important Medical Event Requiring Medical or Surgical Intervention to Prevent 
Serious Outcome An important medical event that may not be immediately life-
threatening or result in death or hospitalization, but based on medical judgment may 
jeopardize the subject and may require medical or surgical intervention to prevent any of 
the outcomes listed above (i.e., death of subject, life-threatening, hospitalization, 
prolongation of hospitalization, congenital anomaly, or persistent or significant 
disability/incapacity).  Examples of such events include allergic bronchospasm requiring 
intensive treatment in an emergency room or at home, blood dyscrasias or convulsions 
that do not result in inpatient hospitalization, or the development of drug dependency or 
drug abuse. 
Spontaneous Abortion Miscarriage experienced by study subject.  
Elective Abortion Elective abortion performed on study subject.

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7.2
Severity 
The physician will use the following definitions to rate the severity for any adverse event 
being collected as an endpoint/data point in the study and for all serious adverse events.
Mild The adverse event is transient and easily tolerated by the subject.  
Moderate The adverse event causes the subject discomfort and interrupts the subject's 
usual activities.  
Severe The adverse event causes considerable interference with the subject's usual 
activities and may be incapacitating or life-threatening.
7.3
Relationship to Pharmaceutical Product 
The physician will use the following definitions for any adverse event being collected as 
an endpoint/data point in the study and for all serious adverse events, to assess the 
relationship of the adverse event to the use of the pharmaceutical product:  
Probably Related An adverse event has a strong temporal relationship to study drug or 
recurs on re-challenge and another etiology is unlikely or significantly less likely.  
Possibly Related An adverse event has a strong temporal relationship to the study drug 
and an alternative etiology is equally or less likely compared to the potential relationship 
to study drug.  
Probably Not Related An adverse event has little or no temporal relationship to the 
study drug and/or a more likely alternative etiology exists. 
Not Related An adverse event is due to an underlying or concurrent illness or effect of 
another drug and is not related to the study drug (e.g., has no temporal relationship to 
study drug or has a much more likely alternative etiology).  

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If an investigator's opinion of possibly, probably not, or not related to pharmaceutical 
product is given, an alternate etiology must be provided by the investigator for the 
adverse event.
7.4
Serious Adverse Event Collection Period
Serious adverse events will be reported to AbbVie from the time the physician obtains the 
patient’s authorization to use and disclose information (or the patient’s informed consent) 
until 30 days or 5 half-lives following the intake of the last dose of physician-prescribed 
treatment.
7.5
Serious Adverse Event Reporting
For serious adverse events from patients using an AbbVie product, the physician will 
notify the AbbVie contact person identified below within 24 hours of the physician 
becoming aware of the event. 
Medical Information
AbbVie Corporation 
8401 Trans-Canada Highway
St-Laurent, Qc H4S 1Z1 
The reporting physician must state that he/she is involved in the P12-678 trial and must
report SAE to medical information.

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7.6
Pregnancy Reporting
In the event of pregnancy, the physician will notify by telephone only the AbbVie contact 
identified in Section 7.5 within 24 hours of the physician becoming aware of the 
pregnancy. 
7.7
Unusual Failure in Efficacy 
Lack of efficacy is the failure of health product to produce the expected intended benefit. 
The Canadian Food and Drug Act and Regulations require that manufacturers report 
cases of unusual failure in efficacy to Health Canada for new drugs in the post-marketing 
setting, including in Phase IV studies. 
Physicians should exercise clinical judgment to determine if the lack of efficacy is related 
to the drug itself, rather than one of treatment selection or disease progression since 
health products cannot be expected to be effective in 100% of the subjects. 
The Investigator shall report all cases of unusual failure in efficacy coincident with the 
use of the study drug to AbbVie within 24 hours by telephone at 
 or by 
email at 
.  When calling this number, the Investigator will 
identify himself as an Investigator of the study reporting an unusual failure in efficacy to 
Medical Information. If there is any need to fax information, the Investigator will use the 
following fax number: Fax: 
.
8.0
Ethics and Quality
The study will be submitted for review and approval at a central ethics committee, local 
ethics review boards, as required for individual sites and the College of Physicians and 

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Surgeons of Alberta. The boards will review the study protocol, informed consent and 
patient questionnaires. A list of participating physicians will be provided to the review 
boards. No study activities will be undertaken prior to obtaining the relevant approval of 
the Independent Ethics Review Boards. 
Prior to being enrolled in the study and the conduct of any study assessments, written 
informed consent will be obtained from the patient or designated legal representative. 
The investigator will explain the study to the patient along with the requirements for 
completion of the self administered questionnaires. The informed consent will provide 
permission for the patient’s data to be used anonymously in the study. In addition, 
written authorization will be provided by the patient to authorize contact by the study 
personnel at specified coordinates. 
Patient confidentiality will be protected at all times by using a randomly generated 
patient study identification number that will identify each unique patient. The name, 
address, telephone numbers, provincial insurance numbers, hospital record numbers or 
any other identifier will NEVER be entered in any page of the Case Report Form, 
questionnaire or return envelope. The link between patient contact information and the 
patient study identification number will be kept in a secure location and password 
protected computer folder that is separated from other information and is accessed only 
by authorized study personnel.
Prior to being included in the study all sites will be assessed for compliance with local 
requirements for the practice of medicine including validation of the physician’s license 
and specialization certificates. In addition, all site personnel will be educated with respect 
to Good Clinical Practices (GCP) and the requirements for data reporting and in particular 
adverse event reporting of the study. Sites with experience in the conduct of clinical 
research will be preferred.
Data quality will be ensured by conducting a study audit, random sample monitoring, 

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logic edit checks and statistical assessments. An audit of 100% of the sites will be 
conducted to ensure that the patients entered in the study fulfill the inclusion and 
exclusion criteria. 
Monitoring with source document verification when possible will be conducted on a 
maximum random 10% sample of the sites. 
Edit checks will be programmed in the data management system by Cato Research. The 
edit checks identify out of range and illogical entries. Edit checks generate queries that 
are reviewed by the project manager who will either proceed with a level I correction or 
will issue a data clarification request to the site. Level I corrections are those that could 
be decided by the project manager or the project scientific director without requiring 
contact with the site. Typical example of level I corrections is the year of the study visit 
date. The criteria for level I corrections will be described in the data management plan. In 
addition a listing of all level I corrections will be transmitted to the study sites at regular 
intervals for confirmation. 
Statistical methods employed to identify out of range or outlying datapoints will include 
frequency distributions, box plots and contingency tables. Statistical analyses to identify 
these issues will be conducted on a regular basis as part of the data management process. 
Patient records with potential errors will be flagged and queries will be generated that 
will be reviewed by the project manager who will determine whether a data clarification 
request should be transmitted to the site.
All data clarification requests will be transmitted to the sites by fax or by email 
depending on the preference of the site investigator. Corrections will be entered into the 
database depending on the response from the site. A patient record will be considered 
close when there are no pending data clarifications. 
Data management for the current study will be conducted on Cato Research system The 

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data management procedures and computer systems used by Cato Research have been 
subjected to regular validation and verification. The data management system developed 
for the current study will be subjected to a study specific audit. In addition, the study will
be audited by the Director of Quality Assurance for compliance with the company and 
study specific standard operating procedures. Compliance with GCP, 21 CRF Part 11 are 
assured through these processes and the Quality Assurance master Plan.
9.0
Case Report Forms
Data collection for the current study will be conducted on traditional paper Case Report 
Forms (CRFs) that will be faxed to the Cato Research Data Collection Center or by using
an Electronic Data Capture (EDC) system. The faxed CRFs will be reviewed and after 
verification the data will be collected in the data base. All edit checks will be 
programmed in the ORACLE Clinical platform and all study databases will be in 
ORACLE. The EDC system will be based on a paper CRF that will be approved by the 
sponsor and the principle investigators.
The study CRF or EDC interface will consist of the following sections:
1.
Baseline / Screening: This will be used to enter all the data collected during the 
baseline / screening visit as described in Table 1 section 6.5.
2.
Follow-Up Visits: These will be labeled as Visit 2 – 6 with the suggested time 
points of 3, 6, 12, 18 and 24 months indicated. However, as mentioned earlier this 
is the recommended schedule of visits and the investigators will be allowed to 
conduct the assessments according to their routine practice and judgment. 
Consequently the investigators will be instructed to use the individual CRF visit 
sections for visits that take place on time period that is nearest to the suggested 
time point. The date of the visit will be clearly indicated. The information 

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collected on these follow up visits are described in detail in Table 1 section 6.5. 
3.
Additional (Non Scheduled) Follow Up Visits: Blank CRF sections will be 
provided for the site investigators to enter the available data from additional 
visits.
4.
End of Study: This will be a separate section of the CRF describing the final status 
of the patient in the study as “completed” or withdrawn. For patients that are 
withdrawn from the study the reason and date will be reported.
All CRF sections will contain the anonymous random site number, patient ID and date of 
the visits.
At the conclusion of the study, the completed signed and dated case report forms for the 
enrolled patients should be provided to the study data management center by the 
investigator for every patient enrolled in the study. Electronic signatures will be used in 
the case of an EDC system. A distinct case report form should be created for each unique 
instance when data is to be collected. ONLY data specified in the protocol should be 
collected and submitted to the study data management center. The investigator or staff 
under his/her supervision must complete the case report forms and neither AbbVie nor 
any agents acting on behalf of AbbVie may complete the case report forms.
10.0
Data Analysis Plan
10.1
Overview: 
The following sections provide a brief overview of the statistical methods used to address
the study objectives. Detailed description of the statistical analyses, any deviation from 
the protocol and assumptions employed will be presented in the Statistical Analysis Plan 
that will be prepared prior to database close and initiation of any statistical analyses. In 

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addition the final sections describe particular considerations relevant to the observational 
nature of the current study. 
10.2
General Considerations: 
Descriptive statistics consisting of the mean, median, standard deviation and 95% 
confidence interval of the mean for continuous scale variables and frequency 
distributions for categorical variables will be produced for the baseline characteristics. 
These descriptive statistics will be produced for the study cohort as a whole and for the 
three treatment cohorts as described in section 6.0. 
Between cohort differences with respect to the baseline parameters will be assessed with 
the Chi-Square statistic for categorical variables and One Way Analysis of variance 
(ANOVA) for continuous scale variables. Variables for which a trend for statistical 
significance (P < 0.15) or clinically important difference (more than 2 – fold) are 
observed will be considered as potential confounders and will be included in the 
multivariate analyses or propensity score development described later. Descriptive 
statistics will be produced for all variables and the changes from baseline when Statistical 
Methods to Address the Study Objectives: 
Between group differences with respect to achieving the primary effectiveness outcome, 
specifically a PGA of “0” or “1” at 24 months will be assessed with simple logistic 
regression analysis and multivariate logistic regression models adjusting for potential 
confounders or the propensity score. A more relevant analysis will be to assess the 
differences between the groups with respect to the time to achieving the end point. For 
this analysis Kaplan Meier based time to event (survival) analysis will be used with the 
log-rank test to assess the statistical significance of the between group differences. Cox’s 
proportional hazards model will also be used to adjust for potential confounders or the 
propensity score. 
Between groups differences with respect to the changes in the BSA, PGA, DLQI, Psoriasis 

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Related Pruritus Assessment VAS, Plaque Psoriasis and Psoriatic Arthritis Pain VAS,
BDI,9SF-12 (second version) WLQ from baseline to 24 months of treatment will be 
assessed with One Way ANOVA or repeated measures, mixed effects general linear model 
adjusting for potential confounders or the propensity score. Planned contrasts will be 
used to assess between group differences at the other follow up time points. Pairwise 
between group comparisons will be adjusted for multiplicity with the Tukey’s Least 
Significance Test.
In order to better assess the impact of the treatment received and changes in the regimen 
the treatment will be handled as a time – dependent covariate in these analyses.
With respect to achieving therapeutic response end points and incidence of articular and
extra-articular manifestations between group differences will be assessed with multi-
variate logistic regression while Cox proportional hazard models will be used to assess 
between group differences with respect to the time of achieving therapeutic response and 
first occurrence of articular and extra–articular manifestations. 
Descriptive statistics will be used to assess the between group and regional differences 
with respect to patient characteristics and disease parameters. Descriptive statistics will 
also be used to assess the practice patterns of Canadian dermatologists in the 
management of patients with moderate to severe PLAQUE PS. The study cohorts will be 
divided into Canadian regions as Quebec, Ontario, Maritimes and Western Canada. 
Underdiagnosis of articular and extra articular manifestations will be assessed by the 
prevalence of existing articular manifestations and a survey of participating physicians 
with respect to their estimates of the prevalence of articular and extra- articular 
manifestations in the patients. 
Safety will be assessed by the incidence of treatment emergent adverse events with 
adjusted relative risks used to compare the three treatment groups.  

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10.3
Sample Size Calculations
Sample size considerations are based on the primary objectives of the study, specifically 
the proportion of patients that achieve a PGA rating of “0” or “1” at 24 months of follow 
up.
The following data and assumptions were used to determine the sample size requirements 
for the study:
x
In the Champion study after 16 weeks of treatment 73% of the patients treated 
with adalimumab, 30% of the patients treated with methotrexate and 11.3% of the 
patients treated with placebo achieved PGA values of 0 or 1 indicating clear or 
minimal disease. 
x
The Champion study was a randomized placebo controlled clinical trial that was 
based on a strict protocol not allowing any concomitant treatment and enrolling a 
very well defined patient population. In the current study we can assume that we 
will observe similar trends in the order of treatment effectiveness, by which 
adalimumab will be superior to traditional systemic agents, which will be superior 
to topical agents. However, due to case mix and use of concomitant medications 
the actual therapeutic effect and difference between groups may be more variable 
and lower than that observed in the CHAMPION study. We can therefore assume 
that due to patient profile, and in order to be conservative,   that the observed 
proportion of patient achieving and maintaining a PGADWPRQWKVZLOO EH
approximately 50%.  A relative reduction of 20% (RR = 0.80) in PGA would be 
considered as the minimum acceptable for clinical importance. Therefore, the 
current study we should be powered to detect a 20% relative reduction between 
adalimumab and traditional systemic agents, and a similar difference between 
systemic and topical agents. It follows that if we assume that the proportion of 
patients treated with adalimumab that achieve PGA  DW VL[ PRQWKV ZLOO EH

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50%, the proportion in the patients treated with traditional systemic agents will be 
40% (RR=0.8) and that in patients treated with topical agents will be 32% (RR =
0.8).
x
For an expected treatment group ratio of 1:1 for adalimumab: traditional systemic 
agents and topical agents a total of 360 (180: 180) patients will be required for 
80% power and two tailed significance of 5%. Assuming a 25% attrition rate and 
allowing for 100 additional patients (10 per variable) in the multivariate analysis 
660 (330:165:165) patients will be recruited.
11.0
Final Report and Publications 
At the end of the study, a study report will be written by the study investigators who will 
also sign the report. This report will contain a description of the objectives of the study 
the methodology of the study and its results and conclusions. The completed case report 
forms and the study report are the confidential property of AbbVie Corporation and will 
not be released to unauthorized individuals in any form (publications or presentations) 
without expressed written approval from AbbVie Corporation. The results of this PMOS
may be published by AbbVie Corporation or by any one of the participating investigators 
after agreement with AbbVie Corporation.

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12.0
References
1. SIVAMANI, R. K., CORREA, G., ONO, Y., BOWEN, M. P., 
RAYCHAUDHURI, S. P., MAVERAKIS, E., Biological Therapy of Psoriasis, 
Indian Journal of Dermatology, California, United States, April-June 2010; 55(2): 
161–170.
2. Psoriasis, http://www.nlm.nih.gov/medlineplus/psoriasis.html, MedlinePlus, 
consulted on July 20th, 2010.
3. X-Plain Psoriasis – Reference Summary, The Patient Education Institute, Inc., 
U.S. National Library of Medicine, NIH National Institutes of Health, 2008.
4. About Psoriasis – Types of psoriasis, 
https://www.psoriasis.org/NetCommunity/SSLPage.aspx?pid=386, National 
Psoriasis Foundation, consulted on July 21st, 2010.
5. About Psoriasis – Causes of psoriasis and triggers, 
https://www.psoriasis.org/NetCommunity/SSLPage.aspx?pid=374, National 
Psoriasis Foundation, consulted on July 21st, 2010.
6. About Psoriasis – Statistics, 
https://www.psoriasis.org/NetCommunity/SSLPage.aspx?pid=372, National 
Psoriasis Foundation, consulted on July 21st, 2010.
7. Psoriasis Statistics, http://www.psoriasis-
aid.com/psoriasis/statistics_of_psoriasis.html, Psoriasis-Aid, consulted on July
22nd, 2010.
8. STERN, R. S., NIJSTEN, T., FELDMAN, S. R., MARGOLIS, D. J., ROLSTAD, 
T., Psoriasis is common, carries a substantial burden even when not extensive, 
and is associated with widespread treatment dissatisfaction, Journal of 
Investigative Dermatology, March 2004; 9(2):136-9.
9. LYNDE, C.W., POULIN, Y., GUENTHER, L., JACKSON, C., The burden of 
psoriasis in Canada: insights from the pSoriasis Knowledge IN Canada (SKIN) 
survey, Journal of cutaneous medicine and surgery, September-October 
2009;13(5):235-52.

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10. GELFAND, J. M., TROXEL, A. B., LEWIS, J. D., KOHLI KURD, S., SHIN, D. 
B., WANG, X., MARGOLIS, D. J., STROM, B. L., The Risk of Mortality in 
Patients With Psoriasis - Results From a Population-Based Study, Archives of 
Dermatology, December 2007;143(12):1493-9.
11. Treating psoriasis – Psoriasis severity, 
https://www.psoriasis.org/NetCommunity/SSLPage.aspx?pid=409, National 
Psoriasis Foundation, consulted on July 23rd, 2010.
12. Treating psoriasis – Topicals, 
https://www.psoriasis.org/NetCommunity/SSLPage.aspx?pid=1546, National 
Psoriasis Foundation, consulted on July 23rd, 2010.
13. Treating psoriasis – Mild psoriasis: topical steroids, 
https://www.psoriasis.org/NetCommunity/SSLPage.aspx?pid=416, National 
Psoriasis Foundation, consulted on July 23rd, 2010.
14. Treating psoriasis – Mild psoriasis: non-steroidal prescription topical treatments, 
https://www.psoriasis.org/NetCommunity/SSLPage.aspx?pid=414, National 
Psoriasis Foundation, consulted on July 23rd, 2010.
15. Treating psoriasis – Phototherapy, 
https://www.psoriasis.org/NetCommunity/SSLPage.aspx?pid=430, National 
Psoriasis Foundation, consulted on July 26th, 2010.
16. Treating psoriasis- Traditional systemic medications, 
https://www.psoriasis.org/NetCommunity/SSLPage.aspx?pid=432, National 
Psoriasis Foundation, consulted on July 26th, 2010.
17. Treating psoriasis – Systemic Medications: Methotrexate, 
https://www.psoriasis.org/NetCommunity/SSLPage.aspx?pid=440, National 
Psoriasis Foundation, consulted on July 27th, 2010.
18. Treating psoriasis – Systemic Medications: Cyclosporine, 
https://www.psoriasis.org/NetCommunity/SSLPage.aspx?pid=435, National 
Psoriasis Foundation, consulted on July 27th, 2010.
19. PARNHAM, M. J., BRUINVELS, J., WEINBERG, J. M., BUCHHOLZ, R., 
TNF-alpha Inhibitors, Birkhäuser, Basel, Switzerland, 113 pages.

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20. MENTER, A., GOTTLIEB, A., FELDMAN, S. R., VAN VOORHEES, A. S., 
LEONARDI, C. L., GORDON, K. B., LEBWOHL, M., KOO, J. Y. M., 
ELMETS, C. A., KORMAN, N. J., BEUTNER, K. R., BHUSHAN, R., 
Guidelines of care for the management of psoriasis and psoriatic arthritis, Journal 
of the American Academy of Dermatology, May 2008; 58(5):826-850.
21. Adalimumab Injection, 
http://www.nlm.nih.gov/medlineplus/druginfo/meds/a603010.html#side-effects,
MedlinePlus, consulted on July 27th, 2010.
22. Menter A., Grifffiths E M “Current and Future management of Psoriasis”: The 
Lancet vol 370, July 21, 2007; pages: 272-370.
23. University of Maryland Medical Center: 
http://www.umm.edu/patiented/articles/what_phototherapy_treatments_psoriasis_
000087_9.htm
24. Saurat, J-H. Stingl, G. Dubertret, L. Papp, K. Langley, R G. Ortonne, J-P. 
Unnebrink, K. Kaul, M. Camez, A. CHAMPION Study Investigators: Efficacy 
and safety results from the randomized controlled comparative study of 
adalimumab vs. methotrexate vs. placebo in patients with psoriasis 
(CHAMPION). British Journal of Dermatology. 158(3):558-66, 2008 Mar
25. Rigopouls D., Gregoriou S., Lazaridou E., Belyayeva E., Apalla Z., makris M., 
katsambas A., Ioannidis D. treatment of nail psoriasis with adlaimumab; an open 
label unblinded study. Journal European Academy of Dermatology and 
Venereology 2010, 24, 530-534.
26. Menter A., Grodon K B., leonardi G., Gu Y., Goldblum O. J AM ACAD 
Dermatol Voulme 63, number 3, 448-456.
27. Gordon K.B., Langley R., Leonarid G., Toth D., Menter MA., kang S., Heffernan 
M., Miller B., Hamlin R., Lim L., Zhong J., Hoffman R., Okun M. Clinical 
response to adalimumab treatment in patients with moderate to severe psoriasis. 
Double blind randomized controlled clinical trial and open label extension study. 
J Am Acad Dermatol 2006;55:598-606.
28. Bongiorino MR., Pistone G., Doukaki S., Arico M. Adalimumab for treatment of 
moderate to severe psoriasis and psoriatic arthritis. Dermatologic Therapy Vol 21, 

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2008, S15-S20
29. Papoutsaki,M, Chimenti M-S. Costanzo A.,Talamonti M, Zangrilli A., Giunta A, 
Bianchi L, Chimenti S. Adalimumab for severe psoriasis and psoriatic arthritis: 
An open-label study in 30 patients previously treated with other biologics. J Am 
Acad Dermatol 2007;57:269-75.

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Appendix A. 
List of Abbreviations and Definition of Terms
AE
Adverse Event
ANOVA
Analysis of Variance
BCG
Bacille Calmette-Guérin
BDI
Beck Depression Inventory
BSA
Body Surface Area
CBC
Complete blood count
CD4 T-cells
Antigenic marker on helper/inducer T cell
CEDAC
Canadian Expert Drug Advisory Committee
CNS
Central Nervous System
CRF
Case Report Form
CRP
C-reactive protein
DLQI
Dermatology Life Quality Index
DNA
Deoxyribonucleic acid
EDC
Electronic Data Capture
ESR
Erythrocyte Sedimentation Rate
FDA
Food and Drug Administration
GCP
Good Clinical Practice
ID
Identification
IFN-Į
Interferon-Alpha
IgG –IgG1
Immunoglobulin
IL
Interleukin
MedDRA
Medical Dictionary for Regulatory Activities
MHC
major histocompatility complex
NDA
non disclosure agreement
PASI
Psoriasis Area and Severity Index
PASQ
Psoriasis and Arthritis Screening Questionnaire
PGA
Physician Global Assessment 
PMOS
Post marketing observational studies
PS
Psoriasis
PsA
Psoriasis Arthritis
PUVA
Psoralen-Ultraviolet A treatment
RNA
Ribonucleic acid
RR
Relative Risk
SAE
Serious Adverse Event

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SF-12
Medical Outcomes Study Short Form 12
T-cells
T Lymphocyte
TFN-Į
7XPRU1HFURVLV)DFWRUĮ
TGF-Į
7UDQVIRUPLQJJURZWKIDFWRUĮ
Th
T-Helper cell
UV
Ultraviolet
UVA
Ultraviolet A
UVB
Ultraviolet B
VAS
Visual Analog Scale
WLQ
Work Limitation Questionnaire