Observational Study in AS and PsA Patients to Evaluate Work Productivity Before and After the Start of Adalimumab Therapy in Daily Practice in Belgium
Conditions: Ankylosing Spondylitis, Psoriatic Arthritis
Sponsor: AbbVie



 
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2.0 
Table of Contents 
1.0 
Title Page .................................................................................. 1 
2.0 
Table of Contents ..................................................................... 2 
3.0 
Introduction ............................................................................. 4 
3.1. 
Ankylosing spondylitis .............................................................................. 4 
3.2. 
Psoriatic arthritis ........................................................................................ 6 
4.0 
Rationale ................................................................................... 8 
5.0 
Study Objectives ...................................................................... 8 
5.1 
Primary Objective ...................................................................................... 8 
5.2 
Secondary Objectives ................................................................................. 9 
5.3 
Primary endpoints: ..................................................................................... 9 
5.4 
Secondary endpoints: ................................................................................. 9 
6.0 
Investigational Plan ............................................................... 10 
6.1 
Selection of Study Population .................................................................. 10 
6.1.1 
Inclusion Criteria ..................................................................................... 11 
6.1.2 
Exclusion Criteria .................................................................................... 11 
6.2 
Number of Patients to be Enrolled ........................................................... 11 
6.3 
Investigator Selection Criteria ................................................................. 11 
6.4 
Study Duration ......................................................................................... 12 
6.5 
Study Conduct .......................................................................................... 12 
6.5.1 
Product Supply ......................................................................................... 12 
6.5.2 
Description of Activities .......................................................................... 12 
6.5.3 
Scores and questionnaires used ................................................................ 15 
7.0 
Adverse Events ....................................................................... 17 
7.1 
Adverse Event Definition and Serious Adverse Event Categories .......... 17 
7.2 
Severity .................................................................................................... 19 

 
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7.3 
Relationship to Pharmaceutical Product .................................................. 19 
7.4 
Serious Adverse Event Collection Period ................................................ 20 
7.5 
Serious Adverse Event Reporting ............................................................ 20 
7.6 
Pregnancy Reporting ................................................................................ 20 
8.0 
Ethics and Quality ................................................................. 21 
9.0 
Case Report Forms ................................................................ 21 
10.0 
Data Analysis Plan ................................................................. 22 
10.1 
Sample Size .............................................................................................. 22 
10.2 
Endpoints ................................................................................................. 24 
10.2.1 
Primary Endpoint ..................................................................................... 24 
10.2.2 
Secondary Endpoints ............................................................................... 24 
10.3 
Statistical Methods ................................................................................... 25 
10.3.1 
Analysis Sets ............................................................................................ 25 
10.3.2 
Statistical Analysis ................................................................................... 25 
11.0 
Final Report and Publications .............................................. 26 
12.0 
References ............................................................................... 27 
13.0 
Appendices ............................................................................. 30 
APPENDIX A: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)............ 30 
APPENDIX B: Disease Activity Index/ 28 joints (DAS 28) ............................................. 32 
APPENDIX C: Health Assessment Questionnaire Disability Index (HAQ-DI) ................ 34 
APPENDIX D: Work Productivity and Activity Impairment - Specific Health 
Problem Questionnaire (WPAI-SHP) ...................................................... 36 
APPENDIX E: Dermatology Life Quality Index (DLQI) .................................................. 38 
APPENDIX F: Health Assessment Questionnaire modified for 
Spondyloarthropathies (HAQ-S) ............................................................. 40 
APPENDIX G: Study Plan ................................................................................................. 43 
APPENDIX H: Informed Consent Form............................................................................ 44 
APPENDIX I:  Investigator’s Agreement .......................................................................... 51 

 
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3.0 
Introduction 
Ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are the major subtypes of 
rheumatic diseases named as spondyloarthritides (SpAs). The most important clinical 
features of this group are inflammatory back pain, asymmetric peripheral oligoarthritis, 
predominantly of the lower limbs, enthesitis and specific organ involvement such as 
anterior uveitis and chronic inflammatory bowel disease.  
 
3.1. 
Ankylosing spondylitis 
Ankylosing spondylitis (AS) is the prototype of SpAs and primarily affects the axial 
skeleton, with a characteristic involvement of the spine and sacroiliac joints, synovitis of 
peripheral joints may occur as well. Pain, stiffness due to inflammation and progressive 
spinal ankylosis that may lead to complete spine rigidity (total spinal ankylosis) are the 
clinical hallmarks of the disease. Inflammation may also affect entheses, heart, lung, 
intestine and eyes. The prevalence of AS appears to be substantially higher than 
previously estimated, approximating 0.9% in Caucasians (1). This resembles the 
prevalence of rheumatoid arthritis (RA), but unlike RA, AS is more common in men than 
in women. The average age at onset of AS is in the third decade, which can necessitate 
treatment for several decades. In addition, due to the early onset, development of 
functional disability and life-time costs, the socioeconomic impairment for subjects with 
active AS is likely to be high. Recent surveys have shown that AS is associated with a 
comparable disability to that observed in RA with substantial direct and indirect costs (2). 
 
Work disability in AS and its costs 
Due to its early onset, chronicity and consequent functional impairment, AS carries a 
significant economic burden, arising from both the direct costs of medical and disability 
care and from indirect costs associated with loss of earnings and decreased productivity. 
The prevalence of work disability in AS patients was found to range from 13 - 46% (3-7). 

 
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A Dutch study reported a significant 11%-reduction in overall participation in the labor 
force, compared with the age matched general population. More than 75% of patients with 
AS who had stopped working were officially recognized as work disabled (8). The 
withdrawal rates from work in patients with AS were reported to be about 3-times higher 
than in the general population (9). Data from a Swedish Registry showed that AS patients 
have an increased risk of sick leave, with a relative risk of 1.8 and median of 30 additional 
sick days per year compared with population-based controls (10). A UK-based study 
suggested that 50% of AS patients at working age lost their job due to AS activity, and of 
those in work 50% were work unstable, at moderate or high risk of job retention problems 
(11). The society costs of lost productivity due to AS were estimated at 3.595 EUR per 
patient per year (12). 
 
Treatment of AS 
Nonsteroidal anti-inflammatory drugs (NSAIDs) and physical modalities are the current 
standard therapy for AS. Evidence exists that NSAIDs treat the symptoms of AS, but it 
has not been confirmed that NSAID therapy reliably influences spinal mobility, acute 
phase reactants (e.g., ESR and CRP) or the long-term disease course with respect to the 
development of ankylosis (13, 14).  
The advent of tumour necrosis factor D (TNF-D) blockade marks the first major 
therapeutic advance in AS since the introduction of NSAIDs. Treatment with anti-TNF-D 
agents has been proven to provide significant improvements in clinical symptoms, 
physical function and patients’ health related quality of life (15). 
Of the available TNF-D antagonists, adalimumab is the first fully human monoclonal 
antibody that binds with a high affinity to both free serum and membrane bound TNF-D. 
Adalimumab therapy has been proven to effectively and long-term reduce the signs and 
symptoms of AS (16, 17), including in patients with total spinal ankylosis (18), and extra-
articular manifestations, such as uveitis (19). Treatment with adalimumab also 
significantly improved physical health status and quality of life (20). A recent post-hoc 

 
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analysis of ATLAS trial (16), which was basically aimed at assessing the factors 
associated with work ability and disability in patients with AS, also demonstrated that 
adalimumab sustains improvements in work outcomes, as measured by Work Productivity 
and Activity Impairment – Specific Health Problem Questionnaire (WPAI-SHP) (21). 
Due to the study design, however, these findings did not allow for a definite conclusion 
that the improvements in work outcomes were a direct result of adalimumab therapy (21). 
 
3.2. 
Psoriatic arthritis 
Psoriatic Arthritis (PsA) is an inflammatory arthropathy that occurs in up to one third of 
patients with psoriasis and is usually diagnosed years after the appearance of psoriatic 
skin disease, but may also precede it.  
Synovitis of peripheral joints is a major feature of PsA, and joint affection can be 
monoarthritic, oligoarthritic, or polyarthritic. More than half of patients with PsA exhibit 
progressive, erosive arthritis that often is associated with functional impairment. PsA may 
also affect the axial skeleton: the spine can be involved in any part, most often at the 
lumbosacral transition and the neck.  
PsA can develop at any time, but for most people it appears between the ages of 30 and 
50, and it affects men and women equally. The overall prevalence of PsA is 
approximately 0.1% (22, 23).  
Work disability in PsA and its costs 
There is a dearth of published pharmacoeconomic studies in PsA, despite increasing 
evidence that affected patients can have significant radiographic joint damage, functional 
impairment, reduced quality of life (QoL) and long-term work disability. Among patients 
treated with anti-TNF agents and registered in the British Society for Rheumatology 
Biologic Register, work disability rates were 39% for PsA patients, 41% for AS patients 
and 49% for those with RA (24). Somewhat lower rates were reported for Norwegian PsA 

 
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patients on either conventional or biologic DMARD (disease modifying anti-rheumatic 
drugs) therapy: work disabled were 32.7% of females and 17.4% of males (25). 
Treatment of PsA 
 
The treatment of PsA is directed at controlling the inflammatory process. Although there 
is no clear correlation between the skin and joint inflammation in every patient, the skin 
and joint aspects of the disease need to be treated simultaneously. Initial treatment 
consists of NSAIDs for joint disease and topical or systemic therapy for the skin. More 
severe disease is likely to require treatment with DMARDs, such as MTX, and intra 
articular steroids. Among second-line treatments used in RA and evaluated in patients 
with PsA are sulfasalazine, MTX, leflunomide, gold, antimalarials, cyclosporine, and 
azathioprine (26).  
Anti-TNF agents are highly effective in treating the signs and symptoms of PsA, 
including dactylitis and enthesitis, and they also suppress structural joint damage and treat 
skin psoriasis (27). 
Treatment with adalimumab, dosed at 40 mg s.c. every other week, showed in placebo 
controlled clinical trials ACR20 response rates of 39-58% and ACR50 response rates of 
25-39% in patients with active PsA who had failed previous standard therapy (45, 46). 
Significant improvements of psoriatic skin changes and disease-related quality of life 
were also noted (28).  
Data on the impact of biologic therapy on work disability and productivity in patients with 
PsA are scarce. A study that determined the cost-effectiveness of anti-TNF treatment in 
patients with RA, PsA and AS in a real-world setting found that the number needed to 
treat (NNT) in order to achieve the minimal clinically important difference in HAQ score 
(decrease by ≥ 0.2) was about 2 for all three evaluated diseases: 1.94 for RA, 1.88 for PsA 
and 2.30 for AS (29). After 14 weeks of treatment with infliximab, median productivity as 
measured on a 0 to 10 visual analog scale improved significantly compared with the 
placebo group (30). Results of the recently published ACCLAIM study in patients with 

 
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PsA on adalimumab therapy demonstrated significant improvements (decreases) from 
baseline to week 12 in 3 of the 4 domains assessed by the Work Limitations 
Questionnaire (WLQ): Physical, Time and Output (31). 
4.0 
Rationale 
Ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are both associated with often 
debilitating clinical symptoms, reduced functional impairment and significant impact on 
quality of life.  As a consequence both diseases imply a significant economic burden, 
arising from both the direct costs of medical and disability. Health economics data 
becomes increasingly important to justify the costs of medicines. 
Very limited data are available about the employment status and the work productivity of 
patients with AS and PsA in Belgium. The same is true for the impact of adalimumab 
treatment on employment status and work productivity. 
The aim of this study is to analyse the employment status and work productivity of 
patients with AS and PsA before and after the start of adalimumab and to look at the 
relationship between employment status, work productivity, disease activity and clinical 
evaluations. 
5.0 
Study Objectives 
5.1 
Primary Objective  
The main objective of the study is to observe in daily practice the evolution of work 
productivity over 18 months in AS and PsA patients after the start of adalimumab 
treatment.  
The following questions will be addressed: 

 
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x What is the employment status of AS and PsA patients with active disease before 
initiation of adalimumab? 
x In the patients who work at baseline, what is their work productivity? 
x Does adalimumab therapy enable people with AS and PsA to return to work or 
work more productively? 
 
5.2 
Secondary Objectives  
x Investigate if there is a difference in evolution of employment status and work 
productivity after initiation of adalimumab treatment between AS and PsA patients 
throughout the study 
x Investigate the relationship between disease activity and employment situation and 
the relationship between clinical evaluations and employment situation at baseline 
and after 18 months   
x Investigate possible correlations between disease activity and work productivity 
and between clinical evaluations and work productivity  
 
5.3 
Primary endpoints: 
Total work productivity impairment (TWPI) due to AS/PsA :18 months versus baseline in 
all patients, measured by the WPAI-SHP questionnaire. (Patient reported outcome)  
5.4 
Secondary endpoints:  
x Total work productivity impairment (TWPI) due to AS and PsA separately: 18 
months versus baseline in all patients, measured by WPAI-SHP questionnaire. 
(Patient reported outcome)  
x Evolution over time of (observed for AS and PsA combined and separately) : 
o Number of patients that are employed at each assessed visit 

 
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o Percentage of missed working hours (absenteeism) due to As/PsA 7 days 
prior to each visit   
o Assessment of the effect of As/PsA on the ability to do regular daily 
activities during the 7 days prior to each visit (activity impairment)  
o Assessment of the effect of As/PsA on productivity while working during 
the 7 days prior to each visit (presenteeism) 
x Health Related Quality of Life (Patient reported outcome) 
o HAQ-DI ( PsA) 
o DLQI (PsA)  
o HAQ-S (AS) 
x Disease activity measures and clinical evaluations: 
o DAS28 (PsA) 
o BSA (PsA)  
o BASDAI (AS)  
o Acute phase reactants (CRP / ESR) 
o Physician assessment of disease activity (VAS)  
o Patient assessment of disease activity (VAS) 
o Patient assessment of pain (VAS) 
 
6.0 
Investigational Plan 
6.1 
Selection of Study Population 
The study population will consist of adult patients with diagnosed AS / PSA in whom 
adalinumab treatment will be initiated. All medications will be prescribed in the usual 
manner in accordance with the terms of the marketing authorization and in line with the 
Belgian reimbursement criteria. 
The patients must provide written informed consent prior to study participation and must 
give written authorization to the investigator to use and/or disclose personal and/or health 
data before entry into this observational study.  

 
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6.1.1 
Inclusion Criteria 
x Patients  ≥18 years and ≤  50 years 
x Diagnosed with AS or PsA 
x Patient newly initiated on adalimumab (according to the Marketing Authorization 
and Belgian reimbursement criteria) 
x Signed Informed Consent 
 
6.1.2 
Exclusion Criteria 
x Any contraindication for adalimumab as specified in the corresponding SmPC 
x Patients previously treated with biologics 
x Patients participating in other AbbVie-sponsored trials 
 
6.2 
Number of Patients to be Enrolled 
It is anticipated to enroll 200 patients in the study. Patients will be enrolled by 
approximately 25 centers in Belgium. Each centre will include on average 8 patients 
during the 12 month recruitment period.  
 
6.3 
Investigator Selection Criteria 
Approximately 20 centers across Belgium will be asked to participate in this study.  
Centers can be University hospitals, regional hospitals, private practices.  
Following criteria will be used when selecting investigators:  
x Experience and interest to participate in observational studies 
x Experience in AS / PsA patient care   

 
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x Sufficient patient potential to include the required number of patients in the study 
x Required availability and resources to participate in this observation study 
x Acceptance of study protocol and study procedures  
 
6.4 
Study Duration 
Data will be collected during routine visits at baseline and afterwards preferably after 3, 6, 
12 and 18 months.  The total duration of the observation period for the study will 
therefore be approximately 18 months.  
Patients can be withdrawn from the study at any time during the study when the patient 
withdraws his/her consent or if the investigator finds it no longer appropriate to keep 
patients in the study. 
6.5 
Study Conduct 
This is a local, post marketing, observational study (PMOS). As this is an observational 
study, no additional visits will be required, no study specific medication will be provided 
and no other interventional procedures additional to those comprising routine clinical 
practice will be performed.    
6.5.1 
Product Supply 
Not applicable.  
6.5.2 
Description of Activities 
The following procedures will be performed  
Screening : 
x Patient information will be explained to the patient and Informed Consent will be 
signed 

 
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x Inclusion/Exclusion criteria will be checked 
 
Baseline : 
Following information (if available) will be collected during the visit:  
x Medical history 
x Demographics (gender, year of birth, race) 
x AS and/or PsA diagnosis  
x Previous & current AS and PsA treatments up to 1 month before inclusion 
x Extra-articular disease manifestations (psoriasis, inflammatory bowel disease, 
uveïtis)  
x Educational background  
x Employment situation  
x Disease activity measures and clinical evaluations : 
For PsA patients  
o DAS28 
o BSA 
o Physician assessment of disease activity (VAS) 
o Patient assessment of disease activity (VAS)  
o Patient assessment of pain (VAS) 
o Acute phase reactants (CRP / ESR) 
For AS patients  
o BASDAI 
o Physician assesment of disease activity (VAS) 
o Patient assesment of disease activity (VAS)  
o Patient assessment of pain (VAS) 
o Acute phase reactants (CRP / ESR) 
x Health related Quality of Life (patient reported outcome) :  
For PsA patients  
o DLQI   
o HAQ - DI 

 
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For AS patients  
o HAQ-S 
x WPAI-SHP (PRO) 
x Serious adverse events 
 
Routine visits (by preference at month 3, 6, 12, 18): 
 
x Following information (if available) will be collected during the visit:  
x Changes in AS and PsA treatment since previous visit  
x Change in employment situation 
x Disease activity measures and clinical evaluations : 
For PsA patients  
o DAS28  
o BSA 
o Physician assessment of disease activity (VAS) 
o Patient assessment of disease activity (VAS)  
o Patient assessment of pain (VAS) 
o Acute phase reactants (CRP / ESR) 
For AS patients  
o BASDAI 
o Physician assesment of disease activity (VAS) 
o Patient assesment of disease activity (VAS)  
o Patient assessment of pain (VAS) 
o Acute phase reactants (CRP / ESR) 
x Health related Quality of Life (patient reported outcome) :  
For PsA patients  
o DLQI   
o HAQ - DI 
For AS patients  
o HAQ-S 

 
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x WPAI-SHP (PRO) 
x Serious adverse events 
 
6.5.3 
Scores and questionnaires used  
Disease Activity Score (DAS): 
The DAS (37) indicates the severity of the RA. The score varies between 0 and 10, with 
10 indicating the highest degree of severity. The DAS is calculated from the following 
data documented on the physician form: 
x Joint status: Number of swollen and tender joints 
x ESR (mm/1. h) or CRP (mg/l) 
x Patient’s assessment of current disease activity (from 0 = inactive to 10 = highly 
active) 
The DAS is calculated by means of a validated algorithm. 
BASDAI 
BASDAI (32) is a simple, self-reported questionnaire that consists of 6 questions on 
disease activity. Each is evaluated by a 100 mm horizontal visual analog (VAS) or 0-10 
numerical rating scale (NRS). In this study, NRS is preferred. Each NRS is scored from 0 
to 10 (0 = no symptoms, 10 = very severe symptoms). The mean of the 2 scores relating to 
morning stiffness is taken. The resulting 0 to 50 score for the overall index is converted to 
0 – 10 scale to give the final BASDAI score. A patient will be considered to have axial 
disease if BASDAI score is > 4. 
Health Assessment Questionnaire (HAQ-DI):  
The HAQ (33) is the internationally most-used instrument for assessing RA-related 
functional impairment. It has been validated in patients with a wide variety of rheumatic 
diseases. In this study, the short HAQ-DI (Disability Index) is administered. The patient 
has to answer 20 questions concerning impairment in daily activities within the following 
8 areas: 

 
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Dressing & Grooming, Arising, Eating, Walking, Hygiene, Reach, Grip, Activities 
Patients assess their functionality over the past week by means of a 4-level scale ranging 
from 0 (without any difficulty) to 3 (unable to do). The highest (worst) values will be 
calculated into a mean value which indicates the degree of functional impairment (HAQ 
Disability Index: 0-3). HAQ-DI score is calculated as % in this study. 
Health Assessment Questionnaire modified for Spondyloarthropathies (HAQ-S):  
The HAQ̺S (35) is a modiefied version of the HAQ questionnaire specific for 
Spondyloarthropathies, It is a 25̺item scale on which respondents rate the degree of 
difficulty they have performing tasks in 10 functional areas, with responses ranging from 
0 (no difficulty) to 3 (unable to do). The highest (worst) values will be calculated into a 
mean value which indicates the degree of functional impairment . 
 
Work Productivity and Activity Impairment - Specific Health Problem 
Questionnaire (WPAI-SHP) 
The WPAI (34) is a questionnaire for the self-assessment of work productivity and 
activity impairment. In this observational study, the WPAI-SHP is used which measures 
work productivity and activity impairment with reference to a specific health problem. All 
dimensions relate to the past seven days.  
The following dimensions are measured: 
x Assessment of employment status 
x Assessment of hours missed from work due to health problems and other reasons 
such as vacation or holidays (total number of hours to be indicated) 
x Assessment of hours the patient has actually worked (total number of hours to be 
indicated) 
x Assessment of impairment in work productivity and in regular daily activities 
(2 assessments with 10 levels each) 
 

 
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The WPAI yields four types of scores:  
x ‘activity impairment’ 
x ‘absenteeism’ (work time missed) 
x ‘presenteeism’ (impairment at work/reduced on-the-job effectiveness) and  
x ‘work 
productivity 
loss’ 
(overall 
work 
impairment/absenteeism 
plus 
presenteeism).  
x Scores are transformed into percentages. Higher scores indicate greater 
impairment. 
 
Dermatology Life Quality Index (DLQI):  
The DLQI (36) is a 10-item, self-administered questionnaire which aims to measure the 
impact of skin disease on adult patients’ quality of life. The following 4 dimensions are 
measured: 
x Skin discomfort  
x Self-confidence 
x Occupational and leisure activities 
x Social interaction 
 
 
7.0 
Adverse Events 
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 

 
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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 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 
that 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  
An important medical event that may not be 
immediately life-threatening or result in death or 
hospitalization, but based on medical judgment may 

 
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  Serious Outcome: 
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).  Additionally, any elective or 
spontaneous abortion or stillbirth is considered an 
important medical event.  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. 
 
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 investigator will use the following definitions to assess the relationship of the adverse 
event to the use of study drug: 
Reasonable 
Possibility 
An adverse event where there is evidence to suggest a causal 
relationship between the study drug and the adverse event. 
No Reasonable 
Possibility 
An adverse event where there is no evidence to suggest a causal 
relationship between the study drug and the adverse event. 
 

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If an investigator's opinion of no reasonable possibility of being related to study drug 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 
In the event of a serious adverse event occurring in a patient treated with Humira, whether 
considered related to Humira or not, the physician will notify the AbbVie contact 
dentified below by faxing the completed SAE form within 24 hours of the physician 
becoming aware of the event. 
7.6 
Pregnancy Reporting 
In the event of a pregnancy occurrence in the patient, the physician will notify the AbbVie 
contact person identified in Section 7.5 within 24 hours of the physician becoming aware 
of the pregnancy 

 
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8.0 
Ethics and Quality 
Study approval by an Independent Ethics Committee will be obtained before initiating the 
study. The study will be run according to GCP/ICH guidelines and local regulatory 
regulations. Each patient will receive appropriate explanation and sign an Informed 
Consent Form prior to enrollment into the study. Since this study is a post-marketing 
observational study, a Clinical Trial Authorization from the Competent Authorities is not 
required. 
To ensure data quality the study will be monitored on-site by AbbVie. The case report 
forms will be reviewed periodically for completeness, legibility and acceptability by 
AbbVie personnel (or their representatives).  AbbVie (or their representatives) will be 
allowed access to all source documents in order to verify case report form entries. To 
ensure data quality CRF entries will be verified by the Abbott monitor against source 
documents for a sample of the patients.   
 
9.0 
Case Report Forms 
The investigator or staff under his/her supervision will complete case report forms 
according to the protocol.  Only data specified in the protocol should be collected and 
submitted to AbbVie. All information written on the case report forms will also be 
reflected in the subject’s source documents. 
Case report forms will be supplied by AbbVie.  These forms will be used to transmit 
information collected during the study to AbbVie and regulatory authorities, as applicable.  
Case report forms must be completed for each subject enrolled in this study.  All case 
report forms must be legible and completed in indelible blue or black ballpoint ink.  Any 
necessary corrections are to be made by drawing a single line through the incorrect entry 
and writing in the revision, and must be initialed and dated by the investigator or his/her 
representative.  Data are not to be obliterated by blacking out, using correction fluid or by 

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erasing the original entry.  If the reason for the correction is not obvious, a brief 
explanation (e.g., transcription error) should accompany the change.  All information 
written on the case report forms must also be reflected in the subject source documents . 
The investigator will review the case report forms for completeness and accuracy and sign 
and date each set of case report forms where indicated.  The case report forms will be 
reviewed periodically for completeness, legibility and acceptability by AbbVie personnel 
(or their representatives).  AbbVie (or their representatives) will be allowed access to all 
source documents in order to verify case report form entries. 
Once the original case report form has been removed from the site, all changes must be 
made via the appropriate change form specified by AbbVie.  The principal investigator 
will review the change form for completeness and accuracy and sign and date the change 
form where indicated. 
10.0 
Data Analysis Plan 
The statistical analysis will be performed using SAS software, Version 9.2 or later. 
A detailed analysis plan will be developed with the vendor 
before database lock. 
10.1 
Sample Size 
The main objective of this study is to observe the working status in AS and PsA patients 
before and after the start of adalimumab therapy in daily practice.  The primary variable is 
the change in total work productivity impairment (TWPI) due to AS/PsA between 
baseline and Month 18.  The change will be evaluated in a descriptive way by means of 
the mean change observed in the study and its 95% confidence interval. 

 
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The number of patients to be enrolled (200) was determined on the basis of the recruiting 
capacity of the participating investigational sites (approximately 25) during the foreseen 
recruitment period of 12 months. 
Based on data from Reilly et al (7) it is estimated that about 65% of the patients of the 
study population are working and therefore evaluable for work productivity impairment.  
Supposing that 80% of the employed patients have data available over an 18 month 
period, the mean change in TWPI will be estimated on the basis of data for about 100 
patients. 
Based on data from Kimball (9), it is estimated that the standard deviation of the change 
in TWPI will be about 23.8.  Since this estimate is based upon a 16 week treatment period 
and the estimate to be made is for an 18 month treatment period, 95% confidence intervals 
are also calculated for a somewhat more important standard deviation, arbitrarily set equal 
to 30.0. 

 
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The table below contains 95% confidence intervals on the mean change for some possible 
mean changes (-10.0, -15.0 and -20.0), and for standard deviations (SD) of 23.8 and 30.0, 
supposing data will be available for 100 patients: 
Mean change     SD             95% CI 
     -10.0             23.8        [-14.7 ;   -5.3] 
     -15.0             23.8        [-19.7 ; -10.3] 
     -20.0             23.8        [-24.7 ; -15.3] 
     -10.0             30.0        [-16.0 ;   -4.0] 
     -15.0             30.0        [-21.0 ;   -9.0] 
     -20.0             30.0        [-26.0 ; -14.0] 
These intervals show that quite precise estimates can be obtained of the change in TWPI 
on the basis of the planned sample size. 
 
10.2 
Endpoints 
10.2.1 
Primary Endpoint 
The primary efficacy variable is the change in total work productivity impairment (TWPI) 
due to AS/PsA between baseline and Month 18. 
10.2.2 
Secondary Endpoints 
x TWPI due to AS at Months 3, 6, 12, and 18 
x TWPI due to PsA at Months 3, 6, 12, and 18 
x TWPI due to AS or PsA at Months 3, 6, and 12 
x Evolution over time of : 
o Number of patients that are employed at each assessed visit 
o Percentage of missed working hours (absenteeism) due to AS/PsA, as 
measured by TWPI AS/PsA 7 days prior to each visit   

 
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o Assessment of the effect of AS/PsA on the ability to do regular daily 
activities during the 7 days prior to each visit (activity impairment)  
o Assessment of the effect of AS/PsA on productivity while working during 
the 7 days prior to each visit (presenteeism). 
x Health Related Quality of Life (patient reported outcome) recorded at each visit 
o HAQ-S (AS) 
o HAQ-DI (PsA) 
o DLQI (PsA) 
x Disease activity measures and clinical evaluations recorded at each visit: 
o BASDAI (AS) 
o DAS28 (PsA) 
o BSA (PsA) 
o Acute phase reactants (CRP / ESR) 
o Physician assessment of disease activity (VAS)  
o Patient assessment of disease activity (VAS) 
o Patient assessment of pain (VAS). 
 
10.3 
Statistical Methods 
10.3.1 
Analysis Sets 
The statistical analysis will primarily be based on the Per Protocol analysis set consisting 
of the patients without major protocol violations.  The TWPI-SHP data will also be 
analyzed on the Intention to Treat set. 
10.3.2 
Statistical Analysis 
The study is essentially descriptive.  The numerical variables will be analyzed applying 
descriptive statistics (mean, 95% confidence interval on the mean, standard deviation, 
minimum, 1st quartile, median, 3rd quartile, maximum, number of observations).  
Quantitative variables will be described by means of frequencies and percentages for the 

 
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different categories.  For the variables recorded for both AS and PsA patients the 
descriptions will be given for all patients as well as separately for each subgroup. 
The analysis of the evolution of the work productivity data, the health-related quality of 
life scores, and the disease activity measures and clinical evaluations will be based upon 
data collected during time windows around the foreseen routine study visits. 
The relationship between disease activity and work status and between clinical 
evaluations and work status will be evaluated by comparing the onset data for patients 
currently employed and patients not employed at the baseline visit, and by comparing the 
data from the 18 month time window for patients currently employed and patients not 
employed at the corresponding visit. 
The relationship between disease activity and work productivity and between clinical 
evaluations and work productivity will be evaluated on the basis of the correlations with 
the TWPI for the baseline data. 
11.0 
Final Report and Publications 
Please refer to your investigator site contract for specific information related to 
publication practices. AbbVie abides by the PhRMA Principles on Conduct of Clinical 
Trials and Communication of Clinical Trial results. Our registrations and results 
disclosure adhere to all relevant laws. 

 
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12.0 
References 
1. Braun J, Bollow M, Remlinger G, Eggens U, Rudwaleit M, Distler A, et al. 
Prevalence of spondyloarthropathies in HLA-B27 positive and negative blood 
donors. Arthritis Rheum 1998; 41: 58-67. 
2. Zink A, Braun J, Listing J, Wollenhaupt J. Disability and handicap in rheumatoid 
arthritis and ankylosing spondylitis - results from the German rheumatological 
database. J Rheumatol 2000; 27: 613-22. 
3. Barlow JH, Wright CC, Williams B, Keat A. Work disability among people with 
ankylosing spondylitis. Arthritis Rheum 2001; 45: 424-9. 
4. Boonen A, Chorus A, Miedema H, van der Heijde D, van der Tempel H, van der 
Linden S. Employment, work disability, and work days lost in patients with 
ankylosing spondylitis: a cross-sectional study of Dutch patients. Ann Rheum Dis 
2001; 60: 353-8. 
5. Forejtova S, Mann H, Stolfa J, Vedral K, Fenclova I, Nemethova D et al. Factors 
influencing health status and disability in patients with ankylosing spondylitis in 
the Czech Republic. Clin Rheumatol 2008; 27: 1005-13. 
6. Ward RM; Reveille JD, Learch TJ, Davis JC Jr, Weisman MH. Impact of 
ankylosing spondylitis on work and family life: comparisons with US population. 
Arthritis Rheum 2008; 59: 497-503. 
7. Ariza-Ariza R, Hernandez-Cruz B, Collantes E, et al. Work disability in patients 
with ankylosing spondylitis. J Rheumatol 2009; 36: 2512-16. 
8. Chorus AM, Boonen A, Miedema HS, et al. Employment perspectives of patients 
with ankylosing spondylitis. Ann Rheum Dis 2002; 61: 693-9. 
9. Boonen A, Chorus A, Miedema A, et al. Withdrawal from labour force due to 
work disability in patients with ankylosing spondylitis. Ann Rheum Dis 2001; 60: 
1033-9. 
10. Strombeck B, Jacobsson LT, Bremander A, et al. Patients with ankylosing 
spondylitis have increased sick leave – a registry-based case-control study over 7 
years. Rheumatology (Oxford) 2009; 48: 289-92. 
11. Barkham N, Kong KO, Tennant A, et al. The unmet need for anti-tumor necrosis 
factor (anti-TNF) therapy in ankylosing spondylitis. Rheumatology 2005; 44: 
1277-81. 
12. Boonen A. A review of work-participation, cost-of-illness and cost-effectiveness 
studies in ankylosing spondylitis. Nat Clin Pract Rheumatol 2006; 2: 546-53.  
13. Maksymowych WP. Treatment of ankylosing spondylitis. Rakel and Bope: Conn's 
Current Therapy, W. B. Saunders Company, 2001; 1021- 3.  

 
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14. Wanders A, et al. Nonsteroidal anti-inflammatory drugs reduce radiographic 
progression in patients with ankylosing spondylitis: A randomized clinical trial. 
Arthritis Rheum 2005; 52: 1756- 65. 
15. Heldmann F, Dybowski F, Saracbasi-Zender E, Fendler C, Braun J. Update on 
biologic therapy in the management of axial spondyloarthritis. Curr Rheumatol 
Rep 2010; 12: 325-31. 
16. van der Heijde D, Kivitz A, Schiff MH, et al. Efficacy and safety of adalimumab 
in patients with ankylosing spondylitis. Arthritis Rheum 2006; 54: 2136-46. 
17. van der Heijde D, Schiff MH, Sieper J, et al. Adalimumab effectiveness for the 
treatment of ankylosing spondylitis is maintained for up to 2 years: long-term 
results from the ATLAS trial. Ann Rheum Dis 2009; 68: 922-9. 
18. van der Heijde D, Pangan AL, Schiff MH, et al. Adalimumab effectively reduces 
the signs and symptoms of active ankylosing spondylitis in patients with total 
spinal ankylosis. Ann Rheum Dis 2008; 67: 1218-21. 
19. Rudwaleit M; Rodevand E, Holck P, et al. Adalimumab effectively reduces the 
rate of anterior uveitis flares in patients with active ankylosing spondylitis: results 
of a prospective open-label study. Ann Rheum Dis 2009; 68: 696-701. 
20. Davis JC Jr, Revicki D, van der Heijde DMF, et al. Health-related quality of life 
outcomes in patients with active ankylosing spondylitis treated with adalimumab: 
results from a randomized controlled study. Arthritis Rheum 2007; 57: 1050-7. 
21. Maksymowych WP, Gooch KL, Wong RL, et al. Impact of age, sex, physical 
function, health-related quality of life, and treatment with adalimumab on work 
status and work productivity of patients with ankylosing spondylitis. J Rheumatol 
2010; 37: 385-92. 
22. Boumpas DT, Illei GG, Tassiulas IO. Psoriatic arthritis. In: Klippel JH, Crofford 
LJ, Stone JH, Weyand CM, editors. Primer on the Rheumatic Diseases. Edition 12. 
Georgia: Arthritis Foundation, 2002: 233-238.  
23. Gladman DD. Psoriatic arthritis: Recent advances in pathogenesis and treatment. 
Rheum Dis Clin North Am 1992;18(1):247-56. 
24. Verstappen SMM, Watson KD, Lunt M et al. On behalf of the BSR Biologics 
Register. Rheumatology 2010; 49: 1570-77. 
25. Wallenius M, Skomsvoll JF, Koldingsnes W et al. Work disability and health-
related quality of life in males and females with psoriatic arthritis. Ann Rheum Dis 
2009; 68: 685-9. 
26. Goupille P. Which second line treatments are optimal in psoriatic arthritis? Joint 
Bone Spine 2002;69:244-248. 
27. Poddubnyy DA, Rudwaleit DA. Adalimumab for the treatment of psoriatic 
arthritis. Expert Rev Clin Immunol 2009; 5: 671-81. 

 
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29 
28. Gladman DD, Mease PJ, Cifaldi MA et al. Adalimumab improves joint-related 
and skin-related functional impairment in patients with psoriatic arthritis: patient-
reported outcomes of the Adalimumab Effectiveness in Psoriatic Arthritis Trial. 
Ann Rheum Dis 2007: 66: 163-8. 
29. Barra L, Pope JE, Payne M. Real-world anti-tumor necrosis factor treatment in 
rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis: cost-
effectiveness based on number needed to treat to improve health assessment 
questionnaire. J Rheumatol 2009; 36: 1421-8. 
30. Kavanaugh A, Antoni C, Mease P et al. Effect of infliximab therapy on 
employment, time lost from work, and productivity in patients with psoriatic 
arthritis. J Rheumatol 2006; 33: 2254-9. 
31. Gladman DD for the ACCLAIM Study Investigators: Responses to adalimumab in 
patients with active psoriatic arthritis who have not adequately responded to prior 
therapy: effectiveness and safety results from an open-label study. J Rheumatol 
2010: 37: 1898-906. 
32. Garrett S, Jenkinson T, Kennedy LG et al.. A new approach to defining disease 
status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity 
Index. J Rheumatol 1994; 21: 2286-91. 
33. Buchbinder R et al. Which outcome measures should be used in rheumatoid 
arthritis clinical trials? Clinical and quality-of-life measures' responsiveness to 
treatment in a randomized controlled trial. Arthritis Rheum 1995; 38:1568–80. 
34. Reilly MC, Zbrozek AS, Dukes EM. The validity and reproducibility of a work 
productivity and activity impairment instrument. Pharmacoeconomics. 1993; 4: 
353–65. 
35. Daltroy LH, Larson MG, Roberts NW, Liang MH. A modification of the Health 
Assessment 
Questionnaire 
for 
the 
spondyloarthropathies. 
J 
Rheumatol. 
1990;17(7):946-50 
36. Finlay AY, Khan GK.  Dermatology Life Quality Index (DLQI): A simple 
practical measure for routine clinical use.  Clinical and Experimental Dermatology 
1994; 19: 210-216 
37. Prevoo ML, van’t Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van 
Riel PL. Modified disease activity scores that include twenty-eight-joint counts. 
Development and validation in a prospective longitudinal study of patients with 
rheumatoid arthritis. Arthritis Rheum 1995;38:44–8. 
 

 
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13.0 
Appendices 
APPENDIX A: Bath Ankylosing Spondylitis Disease Activity Index 
(BASDAI) 
Please tick the box which represents your answer to each question. All questions refer to last week.   
 
 
 
1. How would you describe the overall level of fatigue/tiredness you have 
experienced?  
NONE 
 VERY SEVERE  
 
 
 
 
 
2. How would you describe the overall level of AS neck, back or hip pain you have 
had?  
NONE 
 VERY SEVERE 
 
 
 
 
 
3. How would you describe the overall level of pain/swelling in joints other than 
neck, back, hips you have had?  
NONE 
 VERY SEVERE 
 
 
 
 
 
4. How would you describe the overall level of discomfort you have had from any 
areas tender to touch or pressure?  
NONE 
 VERY SEVERE 
 
 
 
 
5. How would you describe the overall level of morning stiffness you have had 
from the time you wake up?  
NONE 
 VERY SEVERE 
 
 
 
 
 
6. How long does your morning stiffness last from the time you wake up?  
 
 
 
 
0 h 
 
 
 
1 h 
 
 
 
2 or more h 

 
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Scoring of the BASDAI:  
The BASDAI Score has a maximum value of 10. 
Translate the time from question 6 into a number from 0-10 (e.g. ¼ h = 1,25; ½ h = 2,5; ¾ h = 
3,75 etc) 
BASDAI Score = 0,2 x (Item 1 + Item 2 + Item 3 + Item 4 + Item 5 + Item 6) 
                                                                                                  2             2 
 
BASDAI score: ..........(0-10) 

 
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APPENDIX B: Disease Activity Index/ 28 joints (DAS 28) 
 
 
 
3. ESR (mm/1rst hr):  
  
    (Erythrocyte Sedimentation Rate)    
 
4. Patient’s global assessment of disease activity (0-100 mm VAS): 
Considering all the ways in which the arthritis may affect your patient at this time, please 
ask him/her the following question: 
 
How active is the disease at the moment? 
 
 
INACTIVE (0)  
 
 
 
 
 
HIGHLY ACTIVE (100) 
 

 
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Formula for calculation of DAS28 ESR:  
DAS28 ESR = 0.56 x √TJ + 0.28 x √SJ + 0.70 x ln (ESR 1
st hour) + 0.014 x Patients global 
assessment of disease 
 
DAS 28 score: .............. 

 
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APPENDIX C: Health Assessment Questionnaire Disability Index (HAQ-DI)   
 
In this section we are interested in learning how your illness affects your ability to 
function in daily life. 
 
Please tick the response which best describes your usual abilities OVER THE PAST 
WEEK: 
 
 
 
Without 
ANY 
Difficulty 
 
With SOME 
Difficulty 
 
With 
MUCH 
Difficulty 
 
UNABLE 
To Do 
 
DRESSING & GROOMING 
 
 
 
 
Are you able to: 
 
 
 
 
- 
Dress yourself, including tying shoelaces and 
doing up buttons? 
 
 
 
 
- 
Wash your hair? 
 
 
 
 
 
 
 
 
 
RISING 
 
 
 
 
Are you able to: 
 
 
 
 
- 
Stand up from a straight chair? 
 
 
 
 
- 
Get in and out of bed? 
 
 
 
 
 
 
 
 
 
EATING 
 
 
 
 
Are you able to: 
 
 
 
 
- 
Cut up your meat? 
 
 
 
 
- 
Lift a full cup or glass to your mouth? 
 
 
 
 
- 
Open a new milk carton ? 
 
 
 
 
 
 
 
 
 
WALKING 
 
 
 
 
Are you able to: 
 
 
 
 
- 
Walk outdoors on flat ground? 
 
 
 
 
- 
Climb up five steps? 
 
 
 
 
 

 
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Please tick the response which best describes your usual abilities OVER THE PAST WEEK: 
 
 
 
Without 
ANY 
Difficulty 
 
With 
SOME 
Difficulty 
 
With 
MUCH 
Difficulty 
 
UNABLE 
To Do 
 
HYGIENE 
 
 
 
 
Are you able to: 
 
 
 
 
- 
Wash and dry your body?  
 
 
 
 
- 
Have a bath? 
 
 
 
 
- 
Get on and off the toilet? 
 
 
 
 
 
 
 
 
 
REACH 
 
 
 
 
Are you able to: 
 
 
 
 
- 
Reach up for and take down a 5 lb object 
(e.g.: a bag of potatoes) from just above 
your head? 
 
 
 
 
- 
Bend down to pick up clothing from the 
floor? 
 
 
 
 
 
 
 
 
 
GRIP 
 
 
 
 
Are you able to: 
 
 
 
 
- 
Open car doors? 
 
 
 
 
- 
Open jars which have been previously 
opened? 
 
 
 
 
- 
Turn taps on and off? 
 
 
 
 
 
 
 
 
 
ACTIVITIES 
 
 
 
 
Are you able to: 
 
 
 
 
- 
Go shopping? 
 
 
 
 
- 
Get in and out of a car? 
 
 
 
 
- 
Do chores such as vacuuming and 
gardening? 
 
 
 
 
 
  
 
 

 
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APPENDIX D: Work Productivity and Activity Impairment - Specific Health 
Problem Questionnaire (WPAI-SHP) 
The following questions ask about the effect of your DISEASE (Ankylosing Spondylitis = AS or 
Psoriatic Arthritis = PsA) on your ability to work and perform regular activities.  Please fill in 
the blanks or circle a number, as indicated. 
 
1.  Are you currently employed (working for pay)?  
_____ NO ___ YES 
  If NO, check “NO” and skip to question 6. 
 
The next questions are about the past seven days, not including today: 
 
2. During the past seven days, how many hours did you miss from work because of problems 
associated with your AS or PsA? Include hours you missed on sick days, times you went in 
late, left early, etc., because of your AS or PsA: 
 
_____ HOURS 
 
 
3. During the past seven days, how many hours did you miss from work because of any other 
reason, such as vacation, or holidays? 
 
_____HOURS 
 
 
4. During the past seven days, how many hours did you actually work? 
 
_____HOURS  (If “0”, skip to question 6.) 
 
5. During the past seven days, how much did your AS or PsA affect your productivity while you 
were working?   
 

 
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Think about days you were limited in the amount or kind of work you could do, days you 
accomplished less than you would like, or days you could not do your work as carefully as 
usual. If AS or PsA affected your work only a little, choose a low number. Choose a high 
number if AS or PsA affected your work a great deal.  
 
Consider only how much AS or PsA affected productivity while you were working. 
AS or PsA had no 
effect on my work 
 
 
 
 
 
 
 
 
 
 
 
AS or PsA 
completely prevented 
me from working 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
CIRCLE A NUMBER 
 
6. During the past seven days, how much did your AS or PsA affect your ability to do your 
regular daily activities, other than work at a job?  By regular activities, we mean the usual 
activities you do, such as work around the house, shopping, childcare, exercising, studying, 
etc.  Think about times you were limited in the amount or kind of activities you could do and 
times you accomplished less than you would like.  If AS or PsA affected your activities only a 
little, choose a low number.  Choose a high number if AS or PsA affected your activities a 
great deal.   
 
Consider only how much AS or PsA affected your ability to do your regular daily activities, 
other than work at a job. 
AS or PsA had no 
effect on my daily 
activities 
 
 
 
 
 
 
 
 
 
 
 
AS or PsA 
completely 
prevented me from 
doing my daily 
activities 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
 
                           CIRCLE A NUMBER  
 
 
WPAI:SHP  V2.0 (US English) 
Reilly MC, Zbrozek AS, Dukes EM.  The validity and reproducibility of a work productivity and 
activity impairment instrument.  PharmacoEconomics 1993;4(5):353-65. 

 
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APPENDIX E: Dermatology Life Quality Index (DLQI) 
 
 
The aim of this questionnaire is to measure how much your skin problem has affected 
your life OVER THE LAST WEEK.  Please check one box for each question. 
 
1.  Over the last week, how itchy, sore, painful or stinging has 
your skin been? 
Very much 
A lot 
A little 
Not at all 
□ 
□ 
□ 
□ 
 
2.  Over the last week, how embarrassed or self conscious have 
you been because of your skin? 
Very much 
A lot 
A little 
Not at all 
□ 
□ 
□ 
□ 
 
3.  Over the last week, how much has your skin interfered with you 
going shopping or looking after your home or yard? 
Very much 
A lot 
A little 
Not at all 
□ 
□ 
□ 
□ 
 
 
 
Not relevant □ 
4.  Over the last week, how much has your skin influenced the 
clothes you wear? 
Very much 
A lot 
A little 
Not at all 
□ 
□ 
□ 
□ 
 
 
 
Not relevant □ 
5.  Over the last week, how much has your skin affected any social 
or leisure activities? 
 
 
 
Very much 
A lot 
A little 
Not at all 
□ 
□ 
□ 
□ 
 
 
 
Not relevant □ 
6. 
Over the last week, how much has your skin made it difficult for 
you to do any sport? 
 
Very much 
A lot 
A little 
Not at all 
□ 
□ 
□ 
□ 
 
 
 
Not relevant □ 

 
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7. 
Over the last week, has your skin prevented you from working 
or studying? 
yes 
no 
□ 
□ 
 
Not relevant □ 
 
If "No," over the last week how much has your skin been a 
problem at work or studying? 
A lot 
A little 
Not at all  
□ 
□ 
□ 
 
8. 
Over the last week, how much has your skin created problems 
with your partner or any of your close friends or relatives?   
Very much 
A lot 
A little 
Not at all 
□ 
□ 
□ 
□ 
 
 
 
Not relevant □ 
9. 
Over the last week, how much has your skin caused any sexual 
difficulties? 
 
Very much 
A lot 
A little 
Not at all 
□ 
□ 
□ 
□ 
 
 
 
Not relevant □ 
10. 
Over the last week, how much of a problem has the treatment 
for your skin been, for example by making your home messy, or 
by taking up time? 
Very much 
A lot 
A little 
Not at all 
□ 
□ 
□ 
□ 
 
 
 
Not relevant □ 
 
Please check you have answered EVERY question. Thank you. 
 
 
 
© AY Finlay, GK Khan, April 1992 
 
 
 
 

 
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APPENDIX F: Health Assessment Questionnaire modified for 
Spondyloarthropathies (HAQ-S) 
 
 

 
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APPENDIX G: Study Plan  
Screening
Baseline
Month 3
Month 6
Month 12
Month 18 
(or term.) 
Informed Consent
i
Inclusion/ Exclusion Criteria
i
Medical History
i
Demographics (gender, year of birth, race)
i
AS & PSA diagnosis  
i
Previous and current AS&PsA treatments
i
Extra articular disease manifestations 
i
i
i
i
i
Educational background
i
Employment situation
i
i
i
i
i
Disease activity measures and clinical 
evaluations : DAS28*, BSA*, physician 
assessment disease activity, acute phase 
reactants (CRP/ESR), BASDAI**, patient 
assessment of disease activity, patient 
assessment of pain
i
i
i
i
i
Healt related quality of life (DLQI*, HAQ-DI*,
HAQ-S**)
i
i
i
i
i
WPAI-SHP
i
i
i
i
i
Serious Adverse Events
i
i
i
i
i
Screening and basline assessments can happen in the same visit  
Follow up visits are according to daily clinicla practice, no additional visits are planned for the study only.   
*only completed for PsA patients  
** only completed for AS patients  

 
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APPENDIX H: Informed Consent Form  
Observational study in Ankylosing Spondylitis and Psoriatic Arthritis 
patients  
to evaluate work productivity before and after the start of Humira therapy  
in daily practice in Belgium 
 
SPACTIVE Study. 
 
 
 
For updated version of the informed consent, please see ICF section of the Investigator 
Site File 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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For updated version of the informed consent, please see ICF section of the Investigator 
Site File 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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For updated version of the informed consent, please see ICF section of the Investigator 
Site File 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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For updated version of the informed consent, please see ICF section of the Investigator 
Site File 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Adalimumab 
P13-990 
FINAL 06 December 2012 
 
 
 
48 
 
 
 
 
For updated version of the informed consent, please see ICF section of the Investigator 
Site File 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Adalimumab 
P13-990 
FINAL 06 December 2012 
 
 
 
49 
 
 
 
 
For updated version of the informed consent, please see ICF section of the Investigator 
Site File 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Adalimumab 
P13-990 
FINAL 06 December 2012 
 
 
 
50 
 
 
 
 
For updated version of the informed consent, please see ICF section of the Investigator 
Site File 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Adalimumab 
P13-990 
FINAL 06 December 2012 
 
 
 
51 
 
APPENDIX I:  Investigator’s Agreement 
 
 
 
1. I  have read this protocol and agree to its content. 
2. I agree to conduct the study as outlined in the protocol and in accordance with all 
applicable regulations and guidelines. 
3. I agree to maintain the confidentiality of all information received or developed in 
connection with the protocol. 
 
 
_______________________________                               __________________ 
Signature of Principal Investigator 
 
 
 
 
 
Date