A Five Year, Post-marketing Observational Study to Follow-up Patients With Rheumatoid Arthritis or Psoriatic Arthritis Who Are Treated With HUMIRA (Adalimumab)
Conditions: Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis
Sponsor: AbbVie (prior sponsor, Abbott)

Protocol No. HUM04-28 
Amendment  3 - 16 February 2006 
1
CONFIDENTIAL INFORMATION 
ABBOTT LABORATORIES 
No use or disclosure outside Abbott is permitted without prior written authorization from Abbott. 
Abbott SA/NV 
Belgium
POST-MARKETING OBSERVATIONAL STUDY (PMOS) 
PROTOCOL HUM04-28 
A five-year, post-marketing observational study to follow-up patients with 
rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis who are 
treated with HUMIRA® (adalimumab)
ProAct
Abbott Number: 
HUM04-28
Investigational Product: 
HUMIRA® (Adalimumab)
Date of protocol: 
14 April 2004 
Date of Amendment 2: 
27 June 2005 
Date of Amendment 3: 
16 February 2006 
Development Phase: 
NA 
Investigator(s):
Multi-center observational study 
(Investigator information on file at  
Abbott SA/NV) 
This study will be conducted in compliance with the protocol and all other applicable 
regulatory and legal requirements. 
/$5

   
Protocol No. HUM04-28 
Amendment  3 - 16 February 2006 
2
CONFIDENTIAL INFORMATION 
ABBOTT LABORATORIES 
No use or disclosure outside Abbott is permitted without prior written authorization from Abbott. 
TABLE OF CONTENTS
1 
 
1 
INTRODUCTION
2 
 
2 
STUDY OBJECTIVES
3 
 
2 
INVESTIGATIONAL PLAN
3.1 
 
3 
Study Population
3.1.1 
 
3 
Inclusion Criteria
3.1.2 
 
4 
Exclusion Criteria
3.2 
 
4 
Safety and Efficacy Variables / Schedule of Assessments
3.2.1 
 
4 
Safety Variables
3.2.2 
 
4 
Efficacy Variables
3.3 
 
6 
Study Procedures
3.3.1 
 
6 
Independent Committee Approval
3.3.2 
 
6 
Informed Consent
3.3.3 
 
7 
Demographics
3.3.4 
 
7 
Patient History
3.3.5 
 
7 
Treatment Modality
3.3.6 
 
7 
Primary Data Collection
3.3.7 
 
8 
Data Report Form (DRF) Completion and Collection
3.4 
 
8 
Withdrawal of Subjects from Study
3.5 
 
8 
Study Management
4 
 
9 
ADVERSE EVENTS / ADVERSE EVENT REPORTING
4.1 
 
9 
Definitions
4.1.1 
 
9 
Adverse Event
4.1.2 
 
10 
Serious Adverse Event

   
Protocol No. HUM04-28 
Amendment  3 - 16 February 2006 
3
CONFIDENTIAL INFORMATION 
ABBOTT LABORATORIES 
No use or disclosure outside Abbott is permitted without prior written authorization from Abbott. 
4.2 
 
11 
Adverse Event Severity
4.3 
 
11 
Relationship to Study Drug
4.4 
 
12 
Adverse Event Reporting
5 
 
12 
DETERMINATION OF SAMPLE SIZE
5.1 
 
12 
Statistical and Analytical Plan
5.1.1 
 
12 
Analyzable Populations
5.1.2 
 
13 
Planned Methods of Statistical Analysis
6 
 
13 
COMPLETION OF STUDY
7 
 
13 
REFERENCES
 
List of In-Text Tables 
Table 1: Schedule of Study Assessments 
6 
List of Appendices
Appendix A Subject Information and Consent Form French Version 
14 
Appendix B Subject Information and Consent Form Dutch Version 
15 
Appendix C Guidance for Joint Evaluation after Preceding Therapeutic Joint 
Procedures 
16 
Appendix D Health Assessment Questionnaire 
17 
Appendix E Pregnancy Report Form 
19
 

   
Protocol No. HUM04-28 
Amendment  3 - 16 February 2006 
1
CONFIDENTIAL INFORMATION 
ABBOTT LABORATORIES 
No use or disclosure outside Abbott is permitted without prior written authorization from Abbott. 
1
INTRODUCTION
HUMIRA(adalimumab), a recombinant, full-length immunoglobulin is the first 
member of a new class of tumour necrosis factor (TNF) antibody compounds, 
developed to contain exclusively human sequences with a very high affinity for 
human TNF.  
To date, more than 3,000 patients with rheumatoid arthritis (RA) have been 
treated subcutaneously with HUMIRA(adalimumab) in controlled trials and 
more than 6,000 in phase IIIb studies and patient named basis programs in 
Europe, North America and Australia. HUMIRA(adalimumab) was administered 
alone or in combination with methotrexate (MTX) or other disease-modifying 
anti-rheumatic drugs (DMARDs) or DMARD combinations.  
HUMIRA(adalimumab) has generally been well tolerated and has demonstrated 
therapeutic efficacy in the treatment of RA compared to placebo treatment. 
HUMIRA(adalimumab) has also shown sustained efficacy in open-label long-
term studies, however the data related to patients treated for four and five years is 
still limited (1, 2). 
RA clinical development is largely completed although a number of long-term 
extension studies and studies for additional indications, e.g. Juvenile Rheumatoid 
Arthritis and early RA are ongoing. 
HUMIRA(adalimumab) was first approved by the Food and Drug 
Administration (FDA) for the treatment of patients with RA in the United States 
of America in December 2002, in Switzerland in April 2003, as well as in several 
Latin American countries. HUMIRA(adalimumab) was approved in the 
European Union in September 2003.  “HUMIRA(adalimumab) is indicated for 
the treatment of moderate to severe, active rheumatoid arthritis in adult patients 
when the response to disease-modifying anti-rheumatic drugs including 
methotrexate 
has 
been 
inadequate. 
To 
ensure 
maximum 
efficacy, 
HUMIRA(adalimumab) 
is 
given 
in 
combination 
with 
methotrexate. 
HUMIRA(adalimumab) can be given as monotherapy in case of intolerance to 
methotrexate or when continued treatment with methotrexate is inappropriate”.  
The data from the Psoriatis arthritis (PsA) controlled clinical trials support the 
conclusion that adalimumab has a favorable benefit/risk ratio in the treatment of 
subjects with PsA. 

   
Protocol No. HUM04-28 
Amendment  3 - 16 February 2006 
2
CONFIDENTIAL INFORMATION 
ABBOTT LABORATORIES 
No use or disclosure outside Abbott is permitted without prior written authorization from Abbott. 
As from August 2005 EMEA has granted the approval for the use of Humira 
(adalimumab) for the treatment of active and progressive psoriatic arthritis in 
adults when the response to previous disease-modifying anti-rheumatic drug 
therapy has been inadequate. 
 
It is expected that as from June 2006 the indications of  HUMIRA(adalimumab) 
will be extended with the treatment  of adults with active ankylosing spondylitis 
who have had an inadequate response to conventional therapy. This amendment 
will be of application after the indication has been approved by EMEA.  
 
For this PMOS, the follow-up observation period is planned for 5 years and is focussed on 
safety 
information 
as 
well 
as 
maintenance 
of 
efficacy 
parameters 
for 
HUMIRA(adalimumab) during normal clinical practice. 
 
2
STUDY OBJECTIVES 
The objectives of this post-marketing observational study are to: 
Observe 
and 
assess 
the 
long-term 
use, 
safety 
and 
efficacy 
of 
HUMIRA(adalimumab), as prescribed by the rheumatologist in a normal clinical 
setting and in accordance with the terms of the European marketing authorization. 
Observational statistics will be made on:  
- Eventual taper-off of concomitant medication (Corticosteroids and NSAIDs) 
when being treated with HUMIRA(adalimumab).  
- Evaluations on patient’s non-medical complications (number of non-working days, number 
of days of hospitalization, …) 
3
INVESTIGATIONAL PLAN 
This is a multi-center, uncontrolled observational study of patients who at the 
time of entry were prescribed with HUMIRA(adalimumab) following normal 
clinical practice, with or without other anti-rheumatic treatments, prior to 
enrollment in this study.  
Patients will be followed for 5 years within the post-marketing observational 
study.  

   
Protocol No. HUM04-28 
Amendment  3 - 16 February 2006 
3
CONFIDENTIAL INFORMATION 
ABBOTT LABORATORIES 
No use or disclosure outside Abbott is permitted without prior written authorization from Abbott. 
Physicians will be provided with a study kit that includes a protocol, patient 
informed consent forms, adverse event report forms, and Data Report Forms 
(DRFs), for each patient to be enrolled.  The participating physician will already 
have provided a prescription to the patient for HUMIRA(adalimumab), along 
with instructions for appropriate use according to the European Union (EU) 
Summary of Product Characteristics (SPC).  
Once the physician has determined that the patient meets the inclusion criteria, 
and the patient has agreed to be included in the observational study, the patient’s 
baseline demographic data, and disease status will be reported in the Baseline 
DRF.  The physician will then follow-up the patient via regular office visits at 
intervals as determined by routine clinical practice or as recommended by 
national guidelines.  
Patient’s safety and efficacy data if they are part of clinical routine will be 
recorded in the DRFs at Baseline, and regular visits which are closest to Month 3, 
Month 6, Month 9, Month 12, Month 18, Month 24, Month 30, Month 36, Month 
42, Month 48, Month 54, and Month 60. While the physician will likely deem it 
appropriate and necessary to have the patient return for intermediate visits during 
the study period, data will be collected via DRFs only at the intervals which 
correspond closely to those described above. Physicians are encouraged to treat 
their patients as they would in their routine clinical practice. If treatment with 
HUMIRA(adalimumab) is permanently discontinued for any reason, patients 
will be discontinued from the study and the reason should be recorded. Physicians 
will be asked to record adverse events up to 3 months after last administration of 
HUMIRA(adalimumab) on the DRF of the next scheduled data collection time. 
3.1
Study Population 
Patients with rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis who 
have been prescribed HUMIRA (adalimumab) within local reimbursement 
guidelines for anti-TNF α’s may be enrolled in the study. 
 
HUMIRA (adalimumab) is used in a normal clinical setting according to label. 
3.1.1
Inclusion Criteria 
x Patients with ongoing HUMIRA (adalimumab) treatment who have been 
prescribed HUMIRA (adalimumab) within local reimbursement guidelines.  

   
Protocol No. HUM04-28 
Amendment  3 - 16 February 2006 
4
CONFIDENTIAL INFORMATION 
ABBOTT LABORATORIES 
No use or disclosure outside Abbott is permitted without prior written authorization from Abbott. 
x Patients must be willing to consent to data being collected and provided to 
Abbott Laboratories 
 
3.1.2
Exclusion Criteria 
x Contraindications according to the SPC 
x Patients who are actually followed in the ReAlise registry (M03-634) 
 
3.2
Safety and Efficacy Variables / Schedule of Assessments 
This is a long-term observational study with the objective of documenting safety 
and efficacy of HUMIRA (adalimumab) in normal rheumatological clinical 
practice.  
3.2.1
Safety Variables 
The physician will be asked to document the adverse events on Adverse Events 
DRFs (see Section 4.0 “Adverse Events/Adverse Event Reporting”).  
For all serious adverse events (SAEs) reports should be sent by fax to Abbott (for 
contact information and fax number see Section 4.4 “Adverse Event Reporting”). 
Special attention for documentation and follow-up is recommended when one of 
the following adverse events occur: 
 malignancy, including lymphoma 
 serious infection, including sepsis, tuberculosis and other opportunistic 
infections 
 lupus-like syndrome 
 demyelinating disease 
 aplastic anaemia and other severe bone marrow suppressions 
 congestive heart failure 
 
In case of pregnancy a pregnancy report form (Appendix E) should be faxed to 
Abbott using the fax number used for SAE forms (Section 4.4) 
3.2.2
Efficacy Variables 
Data on the following individual parameters will be collected if assessed as part 
of clinical practice at each site: 
- 28 joint assessment 

   
Protocol No. HUM04-28 
Amendment  3 - 16 February 2006 
5
CONFIDENTIAL INFORMATION 
ABBOTT LABORATORIES 
No use or disclosure outside Abbott is permitted without prior written authorization from Abbott. 
- physical function (HAQ) 
- inflammatory parameter (ESR, CRP) 
- concomitant medication 
- change in concomitant steroids, NSAIDs  
- assessment of non-medical complications (number of non-working days, number 
of days of hospitalization, …) 

for patients with polyarticular or oligoarticular erosive psoriatic arthritis: 
-
% of the Body Surface Area (BSA) with psoriatic skin lesions  

for patients with oligoarticular erosive psoriatic arthritis: 
-
Numerical Rating Scale (score of 0 to 10) for the disease activity in 
the most important joint by the patient (0 = no disease activity 
during the previous days, 10 = maximal activity during the 
previous days) 
-
Numerical Rating Scale (score of 0 to 10)  for the disease activity 
in the most important joint by the physician (0 = no disease 
activity during the previous days, 10 = maximal activity during the 
previous days) 

For patients with Ankylosing spondylitis the BASDAI will be measured 
 

   
Protocol No. HUM04-28 
Amendment  3 - 16 February 2006 
6
CONFIDENTIAL INFORMATION 
ABBOTT LABORATORIES 
No use or disclosure outside Abbott is permitted without prior written authorization from Abbott. 
 
Table 1: Schedule of Study Assessments 
Procedure
Day 1 
Month* 3, 6, 9, 12, 18, 
24, 30, 36, 42, 48, 54, 60 
Informed Consent 
 
 
Demographics 
 
 
 
 
Safety Data Collection 
 
 
Efficacy Data Collection 


Concomitant DMARDs, steroids, NSAIDs 

Changes in concomitant DMARDs, steroids, NSAIDs 

Data Report Form Completion 
 
 
* Data collection at regular visits which are closest to time points described  
 
3.3
Study Procedures 
The following procedures will be performed during the study at the time points 
specified in Table 1, Schedule of Assessments. 
3.3.1
Independent Committee Approval 
Should the institution/affiliation, and/or national regulation, require an 
independent committee approval/notification of this protocol, (and related 
informed consent), then it shall be the investigator’s responsibility to secure such 
approval prior to further initiating any study procedures. 
3.3.2
Informed Consent 
All subjects will provide their consent to releasing their information to Abbott 
Laboratories (sponsor) on an informed consent form, that is signed and dated by 
the subject prior to the release of any such information to the sponsor.  Before 
informed consent is obtained, the investigator or designee will explain to the 
subject or the subject’s legally acceptable representative, the nature and purpose 
of the study and the data to be provided to the sponsor. After the informed consent 
form is signed, the original informed consent form will be placed in the subject’s 
medical record and a signed copy should be given to the subject.  A patient 
informed consent template is provided in Appendices A (french version) and B 
(dutch version). 

   
Protocol No. HUM04-28 
Amendment  3 - 16 February 2006 
7
CONFIDENTIAL INFORMATION 
ABBOTT LABORATORIES 
No use or disclosure outside Abbott is permitted without prior written authorization from Abbott. 
3.3.3
Demographics
The physician will determine the patient demographic information at the baseline 
visit and record it in the Baseline DRF.  The demographic information will 
include date of birth (year of birth if restricted by national regulations) and  
gender.  
3.3.4
Patient History 
The physician will determine the patient’s current status at the Baseline visit and 
record it in the Baseline DRF.  The patient’s status will also note concomitant 
conditions and whether or not these conditions are currently treated. Changes in 
concomitant medications being taken to treat RA should also be recorded. 
3.3.5
Treatment Modality 
The treatment modality will include thorough information on all treatments 
prescribed by the physician and received by the patient. Since this is an 
observational study, the subject will be treated in accordance with the 
investigator’s usual and customary medical practice.  Abbott Laboratories will not 
provide any medication or therapy for this study. 
 
3.3.6
Primary Data Collection 
The following safety information will be collected: adverse events and serious 
adverse events. The description of event, start and end date, severity, outcome, 
causal relationship, and action taken will be recorded. 
Data to allow determination of patient’s disease activity will be collected. These 
are 28 joint count of swelling and tenderness (SJC, TJC), physician’s global 
assessment of disease activity, HAQ, ESR and CRP.  These data, if available as a 
result of usual medical practice, will be collected via the DRFs.  
Other Data 
Changes in concomitant DMARDs, steroids, and NSAIDs as well as the 
administration schedule of HUMIRA (adalimumab) should be documented in the 
DRFs.  

   
Protocol No. HUM04-28 
Amendment  3 - 16 February 2006 
8
CONFIDENTIAL INFORMATION 
ABBOTT LABORATORIES 
No use or disclosure outside Abbott is permitted without prior written authorization from Abbott. 
3.3.7
Data Report Form (DRF) Completion and Collection 
All data associated with this study will be collected and reported via DRFs on 2-
part NCR paper or electronically via the web address and password which will be 
provided. If using paper DRFs the top copy of the form should be forwarded to 
the data coordination center, the second copy of the form should be retained at 
site.  
At the baseline visit, the investigator should complete the Baseline Data Report 
Forms by collecting and reporting on the forms all available required information, 
including visit date, demographic data, concomitant diseases and medication, etc. 
If using paper DRFs the enrolment fax should be completed and faxed 
immediately to the data coordination center. 
At subsequent visits corresponding to the schedule of assessments (Table 1), the 
investigator should complete the appropriate DRF by collecting and reporting on 
the forms all available information. Since this is an observational study, data from 
the patient visit following normal clinical practice, which most closely 
corresponds to the recommended schedule of assessment at Month 3, Month 6, 
Month 9, Month 12, Month 18, Month 24, Month 30, Month 36, Month 42, 
Month 48, Month 54, and Month 60 will be accepted. 
If the subject is withdrawn from the study at any time or completes the 5-year observation 
period an Early Termination DRF should be completed.  
3.4
Withdrawal of Subjects from Study 
A subject may withdraw from the study at any time without prejudice. The 
investigator may discontinue any subject’s participation for any reason. If a 
patient withdraws or is withdrawn from the study, such should be noted, along 
with the reason for withdrawal, on the Early Termination DRF. 
3.5
Study Management 
Abbott SA/NV will manage the study, collect all study information via DRFs, and complete 
all statistical analysis of the study, or will contract out parts to a Contract Research 
Organisation (CRO). 

   
Protocol No. HUM04-28 
Amendment  3 - 16 February 2006 
9
CONFIDENTIAL INFORMATION 
ABBOTT LABORATORIES 
No use or disclosure outside Abbott is permitted without prior written authorization from Abbott. 
4
ADVERSE EVENTS / ADVERSE EVENT REPORTING 
The investigator will monitor each subject for clinical and laboratory evidence of 
adverse events on a routine basis throughout the study.  The investigator will 
assess and record any adverse event in detail on the adverse event DRF including 
the date and time of onset, description, severity, time course, duration and 
outcome, relationship of the adverse event to study drug, an alternate etiology for 
events not considered "probably related" to study drug, final diagnosis/syndrome 
(if known) and any action(s) taken.  For adverse events to be considered sporadic, 
the events must be of similar nature and severity.  Adverse events, whether in 
response to a query, observed by study-site personnel, or reported spontaneously 
by the subject, will be recorded. 
All adverse events will be followed to a satisfactory conclusion. 
4.1
Definitions
4.1.1
Adverse Event 
An adverse event is defined as any untoward medical occurrence in a subject or 
clinical investigation subject administered a pharmaceutical product and which 
does not necessarily have a causal relationship with this 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 protocol or 
labeling, as well as from accidental or intentional overdose, drug abuse, or drug 
withdrawal.  Any worsening of a pre-existing condition or illness (except RA) is 
considered an adverse event. Laboratory abnormalities and changes in vital signs 
are considered to be adverse events only if they result in permanent or temporary 
discontinuation of treatment with HUMIRA (adalimumab), necessitate 
therapeutic medical intervention and/or if the investigator considers them to be 
adverse events. 
An elective surgery/procedure scheduled to occur during a study will not be 
considered an adverse event. However, if a pre-existing condition (except RA) 
deteriorates unexpectedly during the trial (e.g., surgery performed earlier than 
planned), then the deterioration of the condition for which the elective 
surgery/procedure is being done will be considered an adverse event.  
 

 
  
Protocol No. HUM04-28 
Amendment  3 - 16 February 2006 
10
CONFIDENTIAL INFORMATION 
ABBOTT LABORATORIES 
No use or disclosure outside Abbott is permitted without prior written authorization from Abbott. 
4.1.2
Serious Adverse Event 
If an adverse event meets any of the following criteria, it is to be reported to 
Abbott as a serious adverse event within 24 hours of occurrence or notification of 
the study site: 
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). 

 
  
Protocol No. HUM04-28 
Amendment  3 - 16 February 2006 
11
CONFIDENTIAL INFORMATION 
ABBOTT LABORATORIES 
No use or disclosure outside Abbott is permitted without prior written authorization from Abbott. 
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. 
 
4.2
Adverse Event Severity 
The investigator will use the following definitions to rate the severity of each 
adverse event: 
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. 
4.3
Relationship to Study Drug 
The investigator will use the following definitions to assess the relationship of the 
adverse event to the use of study drug: 
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. 

 
  
Protocol No. HUM04-28 
Amendment  3 - 16 February 2006 
12
CONFIDENTIAL INFORMATION 
ABBOTT LABORATORIES 
No use or disclosure outside Abbott is permitted without prior written authorization from Abbott. 
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). 
4.4
Adverse Event Reporting 
In the event of a serious adverse event, whether related to HUMIRA 
(adalimumab) or not, the investigator will notify one of the following person by 
faxing the appropriate adverse event form within 24 hours of being made aware of 
the serious adverse event. 
 
5
DETERMINATION OF SAMPLE SIZE 
Since the purpose of this study is to assess the long-term treatment safety, and 
efficacy of patients treated with HUMIRA (adalimumab), as many of these 
patients as are willing to participate in this follow-up will be enrolled. As it is an 
observational study, no inferential statistical techniques will be applied to data.  
5.1
Statistical and Analytical Plan 
5.1.1
Analyzable Populations 
Both the efficacy and the safety analysis will be performed on the set of patients 
who received at least one injection of HUMIRA (adalimumab).  
In addition to the analysis of all patients who received HUMIRA (adalimumab), 
certain subgroups may be defined and summarized, e.g. by age, sex, use of certain 
RA medications. 

 
  
Protocol No. HUM04-28 
Amendment  3 - 16 February 2006 
13
CONFIDENTIAL INFORMATION 
ABBOTT LABORATORIES 
No use or disclosure outside Abbott is permitted without prior written authorization from Abbott. 
5.1.2
Planned Methods of Statistical Analysis
Demographics and Baseline Characteristics 
Demographic and baseline variables will be described by summary statistics. For 
continuous data, n, mean, standard deviation, minimum, 1st quartile, median, 3rd 
quartile, and maximum will be presented. For categorical data, absolute and 
relative frequency will be calculated. 
Safety Analyses 
Adverse events will be analysed by presenting frequency and percentage. 
Furthermore, adverse events of special interest, e.g. serious adverse events, or 
adverse events leading to discontinuation of treatment with HUMIRA 
(adalimumab), will be listed. 
Efficacy Analysis 
The efficacy analysis of continuous variables (e.g. joint count) will be done 
descriptively by presenting summary statistics and confidence intervals. 
6
COMPLETION OF STUDY 
The investigator will conduct this study in compliance with the protocol and all 
other applicable regulatory and legal requirements. Abbott SA/NV may terminate 
this study at any time, either in its entirety or at this site, for reasonable cause 
provided that written notice is submitted at a reasonable time in advance of the 
intended termination. The investigator may also terminate the study at their site 
for reasonable cause, after providing written notice to Abbott SA/NV a reasonable 
time in advance of the intended termination. 
 
7
REFERENCES
1.  
Breedveld FC, Allaart CF, Rau R, Herborn G, van Riel PLCM, van de Putte LBA, Schattenkirchner 
M, Kupper H: Sustained efficacy over 4 years with adalimumab in patients with active rheumatoid 
arthritis. Ann Rheum Dis 2003; 62 (suppl 1): 169, abstract THU0197.  
 
2.  
Burmester GR, van de Putte LBA, Rau R, Schattenkirchner M, Hartz D, Kupper H: Sustained efficacy 
of adalimumab monotherapy for more than four years in DMARD-refractory RA. Ann Rheum Dis 
2003; 62 (suppl 1): 192-193, abstract THU0275.  
 

 
  
Protocol No. HUM04-28 
Amendment  3 - 16 February 2006 
14
CONFIDENTIAL INFORMATION 
ABBOTT LABORATORIES 
No use or disclosure outside Abbott is permitted without prior written authorization from Abbott. 
Appendix A 
Subject Information and Consent Form French Version 

 
  
Protocol No. HUM04-28 
Amendment  3 - 16 February 2006 
15
CONFIDENTIAL INFORMATION 
ABBOTT LABORATORIES 
No use or disclosure outside Abbott is permitted without prior written authorization from Abbott. 
Appendix B 
Subject Information and Consent Form Dutch Version 

 
  
Protocol No. HUM04-28 
Amendment  3 - 16 February 2006 
16
CONFIDENTIAL INFORMATION 
ABBOTT LABORATORIES 
No use or disclosure outside Abbott is permitted without prior written authorization from Abbott. 
Appendix C 
Guidance for Joint Evaluation after Preceding Therapeutic Joint 
Procedures
 
 
Procedure
Joints will not be assessed for:  
Intraarticular steroid joint injection 
3 months post injection 
Joint synovectomy 
3 months post surgery 
Radiosynoviorthesis 
3 months post synoviorthesis 
Partial joint endoprosthesis, without synovectomy 
3 months post surgery 
Partial joint endoprosthesis and total synovectomy 
no assessment 
Total joint endoprosthesis 
no assessment 
Joint resection 
no assessment 
Joint arthrodesis 
no assessment 
 
 

 
  
Protocol No. HUM04-28 
Amendment  3 - 16 February 2006 
17
CONFIDENTIAL INFORMATION 
ABBOTT LABORATORIES 
No use or disclosure outside Abbott is permitted without prior written authorization from Abbott. 
Appendix D 
Health Assessment Questionnaire
 
 
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? 
 
 
 
 

 
  
Protocol No. HUM04-28 
Amendment  3 - 16 February 2006 
18
CONFIDENTIAL INFORMATION 
ABBOTT LABORATORIES 
No use or disclosure outside Abbott is permitted without prior written authorization from Abbott. 
 
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? 
 
 
 
 
 

 
  
Protocol No. HUM04-28 
Amendment  3 - 16 February 2006 
19
CONFIDENTIAL INFORMATION 
ABBOTT LABORATORIES 
No use or disclosure outside Abbott is permitted without prior written authorization from Abbott. 
Appendix E 
Pregnancy Report Form 
Investigator Name:  
 
 
Subject Number: 
 
Telephone Number:  
 
 
Subject Initials: 
 
 
 
 
Date of Birth:  
 
Obstetric History
Gravida (present pregnancy not included)________, Para _________, Aborta ________ 
Dosing Information
Dosing of HUMIRA (adalimumab) Day 1 = _________________ 
Birth Control Method
Has the patient used birth control measures? 
 
Yes 
 
No 
 
 
 
Unknown 
 
Pregnancy
Date of 1st positive pregnancy test (   )  serum  
 
(   )  urine 
 
Date of last negative pregnancy test  
 
 
Date of HUMIRA (adalimumab) discontinuation 
 
 
Dates of last menstrual period:       Start: 
 
End: 
 
 
Estimated number of weeks gestation at 1st positive test  ___________ 
Is subject planning to carry pregnancy to term? ______Yes ______ No 
Estimated delivery date  ________________________ 
Comments: 
 
 
 
Investigator Signature:   
 
Date: 
 
Pregnancy Report Sheet (after delivery)
Date of delivery: 
 
 
 
 
Route of delivery: 
 
 
 
 
Birth weight/length:  
 
 
 
 
Gender: 
 
 
 
 
Apgar score: 
 
 
 
 
Complications: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Outcome: 
 
 
 
 
Any abnormalities (major or minor): 
 
 
 
 
 
 
 
 
 
Labor and delivery report (attach)