Long-term Safety and Tolerability Study of Adalimumab in Subjects With Crohn's Disease

• Sponsor: Abbott (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00195715
• Collaborator: (none)
• Enrollment: 777
• Locations: 111
• Duration (Months): 51
• Patients Per Site: 7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

To evaluate the long-term maintenance of response, safety and tolerability of repeated administration of adalimumab in subjects with Crohn's disease who participated in and successfully completed Protocol M02-404 or Protocol M04-691.

Condition or Disease	Intervention/Treatment	Phase
Crohn's Disease	Biological: Adalimumab	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 777 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multi Center, Open Label Study of the Human Anti TNF Monoclonal Antibody Adalimumab to Evaluate the Long Term Safety and Tolerability of Repeated Administration of Adalimumab in Subjects With Crohn's Disease
• Study Start Date: Sep 1, 2004
• Actual Primary Completion Date: Mar 1, 2006
• Actual Study Completion Date: Dec 1, 2008

Outcome Measures

Primary Outcome Measures

1. Percentage of Subjects Achieving Clinical Remission [Week 156]

   Clinical remission was defined as a Crohn's Disease Activity Index (CDAI) score of < 150. The CDAI is a weighted composite score of 8 clinical factors measured over a 1-week period. A lower CDAI score indicates lesser disease severity.

Secondary Outcome Measures

1. Percentage of Subjects Achieving Clinical Remission [Week 48]

   Clinical remission was defined as a Crohn's Disease Activity Index (CDAI) score of < 150. The CDAI is a weighted composite score of 8 clinical factors measured over a 1-week period. A lower CDAI score indicates lesser disease severity.

2. Percentage of Subjects Achieving Clinical Remission [Week 108]

   Clinical remission was defined as a Crohn's Disease Activity Index (CDAI) score of < 150. The CDAI is a weighted composite score of 8 clinical factors measured over a 1-week period. A lower CDAI score indicates lesser disease severity.

3. Percentage of Subjects Achieving Clinical Remission [Week 204]

   Clinical remission was defined as a Crohn's Disease Activity Index (CDAI) score of < 150. The CDAI is a weighted composite score of 8 clinical factors measured over a 1-week period. A lower CDAI score indicates lesser disease severity.

4. Percentage of Subjects Achieving Clinical Response 100 (CR-100) [Week 156]

   A CR-100 is a decrease from baseline in CDAI score of 100 or more points. The CDAI is a weighted composite score of 8 clinical factors measured over a 1-week period. A lower CDAI score indicates lesser disease severity.

5. Percentage of Subjects Achieving Clinical Response 70 (CR-70) [Week 156]

   A CR-70 is a decrease from baseline in CDAI score of 70 or more points. The CDAI is a weighted composite score of 8 clinical factors measured over a 1-week period. A lower CDAI score indicates lesser disease severity.

6. Percentage of Subjects Achieving Steroid-free Clinical Remission [Week 156]

   Steroid-free remission was achieved if the subject stopped taking steroids before the visit and had a Crohn's Disease Activity Index (CDAI) score of <150. The CDAI is a weighted composite score of 8 clinical factors measured over a 1-week period. A lower CDAI score indicates lesser disease severity.

7. Percentage of Subjects Achieving Steroid-free CR-100 [Week 156]

   Steroid-free CR-100 was achieved if the subject stopped taking steroids before the visit and had a decrease from baseline in CDAI score of 100 or more points at that visit. The CDAI is a weighted composite score of 8 clinical factors measured over a 1-week period. A lower CDAI score indicates lesser disease severity.

8. Percentage of Subjects With Fistula Remission [Week 156]

   Fistula remission was defined as the absence of draining fistulas in subjects with fistula present at the preceding study's baseline visit.

9. Percentage of Subjects With Infection [Up to 262 weeks of adalimumab treatment]

10. Percentage of Subjects With Serious Infection [Up to 262 weeks of adalimumab treatment]

    Serious infections are infectious adverse events that meet at least one criterion for a serious adverse event (e.g., death, life threatening event, hospitalization) including tuberculosis (TB), bacterial sepsis, invasive fungal infections (e.g., histoplasmosis), and infections due to other opportunistic pathogens.

11. Percentage of Subjects With Malignancy [Up to 262 weeks of adalimumab treatment]

12. Percentage of Subjects With Lymphoma [Up to 262 weeks of adalimumab treatment]

13. Percentage of Subjects With Nonmelanoma Skin Cancer [Up to 262 weeks of adalimumab treatment]

14. Percentage of Subjects With Malignancy (Excluding Nonmelanoma Skin Cancer and Lymphoma) [Up to 262 weeks of adalimumab treatment]

15. Percentage of Subjects With Malignancy (Including Lymphoma, Excluding Nonmelanoma Skin Cancer) [Up to 262 weeks of adalimumab treatment]

16. Percentage of Subjects With Injection Site Reaction-related Adverse Event [Up to 262 weeks of adalimumab treatment]

    An injection site reaction is any adverse event corresponding to a preferred term beginning with "injection site" excluding injection site arthritis, injection site movement impairment, injection site photosensitivity, injection site joint effusion, injection site joint inflammation, injection site scab, injection site joint pain, or injection site laceration.

17. Percentage of Subjects With Opportunistic Infection (Excluding Tuberculosis) [Up to 262 weeks of adalimumab treatment]

18. Percentage of Subjects With Congestive Heart Failure [Up to 262 weeks of adalimumab treatment]

19. Percentage of Subjects With Demyelinating Disease [Up to 262 weeks of adalimumab treatment]

20. Percentage of Subjects With Hepatic-related Adverse Event [Up to 262 weeks of adalimumab treatment]

21. Percentage of Subjects With Allergic Reaction-related Adverse Event [Up to 262 weeks of adalimumab treatment]

22. Percentage of Subjects With Lupus-like Syndrome [Up to 262 weeks of adalimumab treatment]

23. Percentage of Subjects With Hematologic-related Adverse Event [Up to 262 weeks of adalimumab treatment]

24. Percentage of Subjects With Fatal Adverse Event [Up to 262 weeks of adalimumab treatment]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subject must have successfully completed either the M02-404 (NCT00077779) or M04-691 (NCT00105300) protocol to be eligible for this study

• Diagnosis of Crohn's disease

• Willing and able to give informed consent

Exclusion Criteria:

• Diagnosis of ulcerative colitis

• Women cannot be pregnant or breastfeeding

• Previous history of listeria infection or untreated tuberculosis

• Previous history of cancer other than successfully treated skin cancer or carcinoma-in-situ of the cervix

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site Ref # / Investigator 1894	Huntsville	Alabama	United States	35801
2	Site Ref # / Investigator 1895	Jacksonville	Alabama	United States	35801
3	Site Ref # / Investigator 1787	La Jolla	California	United States	92037
4	Site Ref # / Investigator 1902	Roseville	California	United States	95661
5	Site Ref # / Investigator 1824	San Diego	California	United States	92123
6	Site Ref # / Investigator 1891	San Diego	California	United States	92123
7	Site Ref # / Investigator 1860	Englewood	Colorado	United States	80113
8	Site Ref # / Investigator 6178	Lone Tree	Colorado	United States	80124
9	Site Ref # / Investigator 1904	Wheat Ridge	Colorado	United States	80033
10	Site Ref # / Investigator 1858	Bridgeport	Connecticut	United States	06606
11	Site Ref # / Investigator 1827	Clearwater	Florida	United States	33765
12	Site Ref # / Investigator 1883	Gainesville	Florida	United States	32610
13	Site Ref # / Investigator 1909	Hollywood	Florida	United States	33021
14	Site Ref # / Investigator 1884	Ormond Beach	Florida	United States	32174
15	Site Ref # / Investigator 1786	Winter Park	Florida	United States	32789
16	Site Ref # / Investigator 1912	Atlanta	Georgia	United States	30342
17	Site Ref # / Investigator 1878	Arlington Heights	Illinois	United States	60005
18	Site Ref # / Investigator 2534	Chicago	Illinois	United States	60637
19	Site Ref # / Investigator 1823	Peoria	Illinois	United States	61602
20	Site Ref # / Investigator 1885	Anderson	Indiana	United States	46016
21	Site Ref # / Investigator 1900	Indianapolis	Indiana	United States	46202
22	Site Ref # / Investigator 1890	Indianapolis	Indiana	United States	46237
23	Site Ref # / Investigator 1892	Lexington	Kentucky	United States	40536
24	Site Ref # / Investigator 1906	Metairie	Louisiana	United States	70006
25	Site Ref # / Investigator 1881	Annapolis	Maryland	United States	24101
26	Site Ref # / Investigator 1829	Chevy Chase	Maryland	United States	20815
27	Site Ref # / Investigator 1782	Lutherville	Maryland	United States	21093
28	Site Ref # / Investigator 1887	Silver Spring	Maryland	United States	20901
29	Site Ref # / Investigator 2602	Worcester	Massachusetts	United States	01610
30	Site Ref # / Investigator 1773	Plymouth	Minnesota	United States	55446
31	Site Ref # / Investigator 1856	Rochester	Minnesota	United States	55905
32	Site Ref # / Investigator 1832	Jackson	Mississippi	United States	39202
33	Site Ref # / Investigator 1880	Kansas City	Missouri	United States	64131
34	Site Ref # / Investigator 1853	Mexico	Missouri	United States	65265
35	Site Ref # / Investigator 1888	St. Louis	Missouri	United States	63110
36	Site Ref # / Investigator 1862	St. Louis	Missouri	United States	63128
37	Site Ref # / Investigator 1901	Egg Harbor Township	New Jersey	United States	08234
38	Site Ref # / Investigator 1825	Great Neck	New York	United States	11021
39	Site Ref # / Investigator 1848	Lake Success	New York	United States	11042
40	Site Ref # / Investigator 1841	New York	New York	United States	10028
41	Site Ref # / Investigator 1852	Asheville	North Carolina	United States	28801
42	Site Ref # / Investigator 1882	Charlote	North Carolina	United States	28211
43	Site Ref # / Investigator 1855	Charlotte	North Carolina	United States	28207
44	Site Ref # / Investigator 1911	Raleigh	North Carolina	United States	27612
45	Site Ref # / Investigator 1861	Wilmington	North Carolina	United States	28403
46	Site Ref # / Investigator 1784	Beachwood	Ohio	United States	44122
47	Site Ref # / Investigator 1896	Beaver Creek	Ohio	United States	45440
48	Site Ref # / Investigator 1833	Cincinatti	Ohio	United States	45219
49	Site Ref # / Investigator 1826	Cleveland	Ohio	United States	44106-5066
50	Site Ref # / Investigator 1822	Portland	Oregon	United States	97220
51	Site Ref # / Investigator 1886	Pittsburgh	Pennsylvania	United States	15216
52	Site Ref # / Investigator 1905	Columbia	South Carolina	United States	29204
53	Site Ref # / Investigator 1769	Germantown	Tennessee	United States	38138
54	Site Ref # / Investigator 1907	Nashville	Tennessee	United States	37205
55	Site Ref # / Investigator 1963	Nashville	Tennessee	United States	37232
56	Site Ref # / Investigator 1899	Round Rock	Texas	United States	78681
57	Site Ref # / Investigator 1903	Salt Lake City	Utah	United States	84107
58	Site Ref # / Investigator 6180	Charlottesville	Virginia	United States	22911
59	Site Ref # / Investigator 1783	Danville	Virginia	United States	24541
60	Site Ref # / Investigator 1897	Norfolk	Virginia	United States	23502
61	Site Ref # / Investigator 1850	Spokane	Washington	United States	99204
62	Site Ref # / Investigator 1831	Milwaukee	Wisconsin	United States	53215
63	Site Ref # / Investigator 1849	West Bend	Wisconsin	United States	53095
64	Site Ref # / Investigator 1938	Camperdown	New South Wales	Australia	2050
65	Site Ref # / Investigator 1940	Bedford Park	South Australia	Australia	SA 5042
66	Site Ref # / Investigator 1935	Box Hill	Victoria	Australia	3128
67	Site Ref # / Investigator 1937	Parkville	Victoria	Australia	3050
68	Site Ref # / Investigator 1941	Bonheiden		Belgium	2820
69	Site Ref # / Investigator 5189	Brussels		Belgium	1070
70	Site Ref # / Investigator 2535	Leuven		Belgium	3000
71	Site Ref # / Investigator 1868	Calgary	Alberta	Canada	T2N 4N1
72	Site Ref # / Investigator 1924	Edmonton	Alberta	Canada	T5H 2B9
73	Site Ref # / Investigator 426	Edmonton	Alberta	Canada	T6G2XB
74	Site Ref # / Investigator 1914	Vancouver	British Columbia	Canada	V5Z 1H2
75	Site Ref # / Investigator 1872	Vancouver	British Columbia	Canada	V6Z 1Y6
76	Site Ref # / Investigator 1870	Victoria	British Columbia	Canada	V8V 3M9
77	Site Ref # / Investigator 1874	Winnipeg	Manitoba	Canada	R3A 1R9
78	Site Ref # / Investigator 1873	Halifax	Nova Scotia	Canada	B3H 2Y9
79	Site Ref # / Investigator 1876	Hamilton	Ontario	Canada	L8N 3Z5
80	Site Ref # / Investigator 1875	London	Ontario	Canada	N6A 5K8
81	Site Ref # / Investigator 1772	Toronto	Ontario	Canada	M3N2V7
82	Site Ref # / Investigator 1865	Toronto	Ontario	Canada	M5G 1X5
83	Site Ref # / Investigator 2459	Montreal	Quebec	Canada	H3A 1A1
84	Site Ref # / Investigator 1866	Montreal	Quebec	Canada	H3G 1A4
85	Site Ref # / Investigator 1863	Quebec City	Quebec	Canada	G1S4L8
86	Site Ref # / Investigator 1952	Arhus C		Denmark	8000
87	Site Ref # / Investigator 1922	Odense C		Denmark	5000
88	Site Ref # / Investigator 1964	Amiens		France	80054
89	Site Ref # / Investigator 2458	Lillie Cedex		France	59037
90	Site Ref # / Investigator 1913	Paris		France	74575
91	Site Ref # / Investigator 1942	Kiel		Germany	24105
92	Site Ref # / Investigator 2524	Regensburg		Germany	93053
93	Site Ref # / Investigator 1943	Stuttgart		Germany	D-70376
94	Site Ref # / Investigator 1944	Budapest		Hungary	H-1125
95	Site Ref # / Investigator 1916	Szekszard		Hungary	7100
96	Site Ref # / Investigator 342	Bologna		Italy	40138
97	Site Ref # / Investigator 1945	Rome		Italy	00152
98	Site Ref # / Investigator 1779	Turin		Italy	10 158
99	Site Ref # / Investigator 1919	Amsterdam		Netherlands	1105 AZ
100	Site Ref # / Investigator 1946	Heerlen		Netherlands	6419 PC
101	Site Ref # / Investigator 1948	Szczecin	71-252	Poland
102	Site Ref # / Investigator 1947	Warsaw		Poland	04-349
103	Site Ref # / Investigator 1844	Johannesburg	GT	South Africa	2193
104	Site Ref # / Investigator 1846	Durban	NL	South Africa	4091
105	Site Ref # / Investigator 1763	Cape Town	WC	South Africa	7708
106	Site Ref # / Investigator 341	Madrid		Spain	28040
107	Site Ref # / Investigator 2457	Puerto de Sagunto		Spain	46520
108	Site Ref # / Investigator 1949	Gothenburg		Sweden	41345
109	Site Ref # / Investigator 1778	Stockholm		Sweden	114 86
110	Site Ref # / Investigator 1951	Edinburgh		United Kingdom	EH4 2XU
111	Site Ref # / Investigator 1771	Rotherham		United Kingdom	S60 2UD

Sponsors and Collaborators

• Abbott

Investigators

• Study Director: Anne Camez, MD, Abbott

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00195715
• Other Study ID Numbers: M04-690
• First Posted: Sep 20, 2005
• Last Update Posted: Jul 12, 2011
• Last Verified: Jul 1, 2011

• Additional relevant MeSH terms: Crohn Disease; Adalimumab

Study Results

Participant Flow

Arm/Group Title	Open-label Adalimumab
Arm/Group Description	40 mg by subcutaneous injection every other week or every week
Period Title: Overall Study
STARTED	777
COMPLETED	400
NOT COMPLETED	377

Baseline Characteristics

Arm/Group Title	Open-label Adalimumab
Arm/Group Description	40 mg by subcutaneous injection every other week or every week
Overall Participants	777
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.0 (11.75)
Sex: Female, Male (Count of Participants)
Female	485 62.4%
Male	292 37.6%
Region of Enrollment (participants) [Number]
United States	349 44.9%
Australia	40 5.1%
Belgium	66 8.5%
Canada	197 25.4%
Denmark	18 2.3%
France	24 3.1%
Germany	5 0.6%
Hungary	8 1%
Italy	9 1.2%
Netherlands	10 1.3%
Poland	12 1.5%
South Africa	20 2.6%
Spain	3 0.4%
Sweden	5 0.6%
United Kingdom	11 1.4%

Outcome Measures

1. Secondary Outcome

Title	Percentage of Subjects Achieving Clinical Remission
Description	Clinical remission was defined as a Crohn's Disease Activity Index (CDAI) score of < 150. The CDAI is a weighted composite score of 8 clinical factors measured over a 1-week period. A lower CDAI score indicates lesser disease severity.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

Intent-to-treat, Observed Cases

Arm/Group Title	Open-label Adalimumab
Arm/Group Description	40 mg by subcutaneous injection every other week or every week
Measure Participants	609
Number [Percentage of participants]	59.4 7.6%

2. Secondary Outcome

Title	Percentage of Subjects Achieving Clinical Remission
Description	Clinical remission was defined as a Crohn's Disease Activity Index (CDAI) score of < 150. The CDAI is a weighted composite score of 8 clinical factors measured over a 1-week period. A lower CDAI score indicates lesser disease severity.
Time Frame	Week 108

Outcome Measure Data

Analysis Population Description

Intent-to-treat, Observed Cases

Arm/Group Title	Open-label Adalimumab
Arm/Group Description	40 mg by subcutaneous injection every other week or every week
Measure Participants	462
Number [Percentage of participants]	68.8 8.9%

3. Primary Outcome

Title	Percentage of Subjects Achieving Clinical Remission
Description	Clinical remission was defined as a Crohn's Disease Activity Index (CDAI) score of < 150. The CDAI is a weighted composite score of 8 clinical factors measured over a 1-week period. A lower CDAI score indicates lesser disease severity.
Time Frame	Week 156

Outcome Measure Data

Analysis Population Description

Intent-to-treat, defined as all subjects who received at least 1 dose of study drug; Observed Cases

Arm/Group Title	Open-label Adalimumab
Arm/Group Description	40 mg by subcutaneous injection every other week or every week
Measure Participants	272
Number [Percentage of participants]	69.5 8.9%

4. Secondary Outcome

Title	Percentage of Subjects Achieving Clinical Remission
Description	Clinical remission was defined as a Crohn's Disease Activity Index (CDAI) score of < 150. The CDAI is a weighted composite score of 8 clinical factors measured over a 1-week period. A lower CDAI score indicates lesser disease severity.
Time Frame	Week 204

Outcome Measure Data

Analysis Population Description

Intent-to-treat, Observed Cases

Arm/Group Title	Open-label Adalimumab
Arm/Group Description	40 mg by subcutaneous injection every other week or every week
Measure Participants	15
Number [Percentage of participants]	46.7 6%

5. Secondary Outcome

Title	Percentage of Subjects Achieving Clinical Response 100 (CR-100)
Description	A CR-100 is a decrease from baseline in CDAI score of 100 or more points. The CDAI is a weighted composite score of 8 clinical factors measured over a 1-week period. A lower CDAI score indicates lesser disease severity.
Time Frame	Week 156

Outcome Measure Data

Analysis Population Description

Intent-to-treat, Observed Cases

Arm/Group Title	Open-label Adalimumab
Arm/Group Description	40 mg by subcutaneous injection every other week or every week
Measure Participants	272
Number [Percentage of participants]	85.7 11%

6. Secondary Outcome

Title	Percentage of Subjects Achieving Clinical Response 70 (CR-70)
Description	A CR-70 is a decrease from baseline in CDAI score of 70 or more points. The CDAI is a weighted composite score of 8 clinical factors measured over a 1-week period. A lower CDAI score indicates lesser disease severity.
Time Frame	Week 156

Outcome Measure Data

Analysis Population Description

Intent-to-treat, Observed Cases

Arm/Group Title	Open-label Adalimumab
Arm/Group Description	40 mg by subcutaneous injection every other week or every week
Measure Participants	272
Number [Percentage of participants]	91.2 11.7%

7. Secondary Outcome

Title	Percentage of Subjects Achieving Steroid-free Clinical Remission
Description	Steroid-free remission was achieved if the subject stopped taking steroids before the visit and had a Crohn's Disease Activity Index (CDAI) score of <150. The CDAI is a weighted composite score of 8 clinical factors measured over a 1-week period. A lower CDAI score indicates lesser disease severity.
Time Frame	Week 156

Outcome Measure Data

Analysis Population Description

Intent-to-treat, Subjects with steroid use at baseline of preceding study, Observed Cases

Arm/Group Title	Open-label Adalimumab
Arm/Group Description	40 mg by subcutaneous injection every other week or every week
Measure Participants	103
Number [Percentage of participants]	63.1 8.1%

8. Secondary Outcome

Title	Percentage of Subjects Achieving Steroid-free CR-100
Description	Steroid-free CR-100 was achieved if the subject stopped taking steroids before the visit and had a decrease from baseline in CDAI score of 100 or more points at that visit. The CDAI is a weighted composite score of 8 clinical factors measured over a 1-week period. A lower CDAI score indicates lesser disease severity.
Time Frame	Week 156

Outcome Measure Data

Analysis Population Description

Intent-to-treat, Subjects with corticosteroid use at baseline of preceding study, Observed Cases

Arm/Group Title	Open-label Adalimumab
Arm/Group Description	40 mg by subcutaneous injection every other week or every week
Measure Participants	103
Number [Percentage of participants]	74.8 9.6%

9. Secondary Outcome

Title	Percentage of Subjects With Fistula Remission
Description	Fistula remission was defined as the absence of draining fistulas in subjects with fistula present at the preceding study's baseline visit.
Time Frame	Week 156

Outcome Measure Data

Analysis Population Description

Intent-to-treat, Subjects with fistulas present at baseline of the preceding study, Observed Cases

Arm/Group Title	Open-label Adalimumab
Arm/Group Description	40 mg by subcutaneous injection every other week or every week
Measure Participants	43
Number [Percentage of participants]	55.8 7.2%

10. Secondary Outcome

Title	Percentage of Subjects With Infection
Time Frame	Up to 262 weeks of adalimumab treatment

Outcome Measure Data

Analysis Population Description

Safety population, defined as all subjects who received at least 1 dose of study drug

Arm/Group Title	Open-label Adalimumab
Arm/Group Description	40 mg by subcutaneous injection every other week or every week
Measure Participants	777
Number [Percentage of participants]	80.2 10.3%

11. Secondary Outcome

Title	Percentage of Subjects With Serious Infection
Description	Serious infections are infectious adverse events that meet at least one criterion for a serious adverse event (e.g., death, life threatening event, hospitalization) including tuberculosis (TB), bacterial sepsis, invasive fungal infections (e.g., histoplasmosis), and infections due to other opportunistic pathogens.
Time Frame	Up to 262 weeks of adalimumab treatment

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Open-label Adalimumab
Arm/Group Description	40 mg by subcutaneous injection every other week or every week
Measure Participants	777
Number [Percentage of participants]	10.6 1.4%

12. Secondary Outcome

Title	Percentage of Subjects With Malignancy
Time Frame	Up to 262 weeks of adalimumab treatment

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Open-label Adalimumab
Arm/Group Description	40 mg by subcutaneous injection every other week or every week
Measure Participants	777
Number [Percentage of participants]	4.1 0.5%

13. Secondary Outcome

Title	Percentage of Subjects With Lymphoma
Time Frame	Up to 262 weeks of adalimumab treatment

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Open-label Adalimumab
Arm/Group Description	40 mg by subcutaneous injection every other week or every week
Measure Participants	777
Number [Percentage of participants]	0.1 0%

14. Secondary Outcome

Title	Percentage of Subjects With Nonmelanoma Skin Cancer
Time Frame	Up to 262 weeks of adalimumab treatment

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Open-label Adalimumab
Arm/Group Description	40 mg by subcutaneous injection every other week or every week
Measure Participants	777
Number [Percentage of participants]	1.8 0.2%

15. Secondary Outcome

Title	Percentage of Subjects With Malignancy (Excluding Nonmelanoma Skin Cancer and Lymphoma)
Time Frame	Up to 262 weeks of adalimumab treatment

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Open-label Adalimumab
Arm/Group Description	40 mg by subcutaneous injection every other week or every week
Measure Participants	777
Number [Percentage of participants]	2.3 0.3%

16. Secondary Outcome

Title	Percentage of Subjects With Malignancy (Including Lymphoma, Excluding Nonmelanoma Skin Cancer)
Time Frame	Up to 262 weeks of adalimumab treatment

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Open-label Adalimumab
Arm/Group Description	40 mg by subcutaneous injection every other week or every week
Measure Participants	777
Number [Percentage of participants]	2.4 0.3%

17. Secondary Outcome

Title	Percentage of Subjects With Injection Site Reaction-related Adverse Event
Description	An injection site reaction is any adverse event corresponding to a preferred term beginning with "injection site" excluding injection site arthritis, injection site movement impairment, injection site photosensitivity, injection site joint effusion, injection site joint inflammation, injection site scab, injection site joint pain, or injection site laceration.
Time Frame	Up to 262 weeks of adalimumab treatment

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Open-label Adalimumab
Arm/Group Description	40 mg by subcutaneous injection every other week or every week
Measure Participants	777
Number [Percentage of participants]	22.8 2.9%

18. Secondary Outcome

Title	Percentage of Subjects With Opportunistic Infection (Excluding Tuberculosis)
Time Frame	Up to 262 weeks of adalimumab treatment

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Open-label Adalimumab
Arm/Group Description	40 mg by subcutaneous injection every other week or every week
Measure Participants	777
Number [Percentage of participants]	4.9 0.6%

19. Secondary Outcome

Title	Percentage of Subjects With Congestive Heart Failure
Time Frame	Up to 262 weeks of adalimumab treatment

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Open-label Adalimumab
Arm/Group Description	40 mg by subcutaneous injection every other week or every week
Measure Participants	777
Number [Percentage of subjects]	0

20. Secondary Outcome

Title	Percentage of Subjects With Demyelinating Disease
Time Frame	Up to 262 weeks of adalimumab treatment

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Open-label Adalimumab
Arm/Group Description	40 mg by subcutaneous injection every other week or every week
Measure Participants	777
Number [Percentage of participants]	0.3 0%

21. Secondary Outcome

Title	Percentage of Subjects With Hepatic-related Adverse Event
Time Frame	Up to 262 weeks of adalimumab treatment

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Open-label Adalimumab
Arm/Group Description	40 mg by subcutaneous injection every other week or every week
Measure Participants	777
Number [Percentage of participants]	8.1 1%

22. Secondary Outcome

Title	Percentage of Subjects With Allergic Reaction-related Adverse Event
Time Frame	Up to 262 weeks of adalimumab treatment

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Open-label Adalimumab
Arm/Group Description	40 mg by subcutaneous injection every other week or every week
Measure Participants	777
Number [Percentage of participants]	2.7 0.3%

23. Secondary Outcome

Title	Percentage of Subjects With Lupus-like Syndrome
Time Frame	Up to 262 weeks of adalimumab treatment

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Open-label Adalimumab
Arm/Group Description	40 mg by subcutaneous injection every other week or every week
Measure Participants	777
Number [Percentage of participants]	0.4 0.1%

24. Secondary Outcome

Title	Percentage of Subjects With Hematologic-related Adverse Event
Time Frame	Up to 262 weeks of adalimumab treatment

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Open-label Adalimumab
Arm/Group Description	40 mg by subcutaneous injection every other week or every week
Measure Participants	777
Number [Percentage of participants]	1.5 0.2%

25. Secondary Outcome

Title	Percentage of Subjects With Fatal Adverse Event
Time Frame	Up to 262 weeks of adalimumab treatment

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Open-label Adalimumab
Arm/Group Description	40 mg by subcutaneous injection every other week or every week
Measure Participants	777
Number [Percentage of participants]	0.3 0%

Adverse Events

Time Frame	Up to 262 weeks of adalimumab treatment (includes adalimumab treatment in previous study)
Arm/Group Title	Open-label Adalimumab
Arm/Group Description	40 mg by subcutaneous injection every other week or every week
All Cause Mortality
	Open-label Adalimumab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Open-label Adalimumab
	Affected / at Risk (%)	# Events
Total	296/777 (38.1%)
Blood and lymphatic system disorders
Anaemia	4/777 (0.5%)
Microcytic anaemia	1/777 (0.1%)
Pancytopenia	1/777 (0.1%)
Cardiac disorders
Angina unstable	1/777 (0.1%)
Myocardial infarction	1/777 (0.1%)
Palpitations	1/777 (0.1%)
Tachyarrhythmia	1/777 (0.1%)
Ear and labyrinth disorders
Tympanic membrane perforation	1/777 (0.1%)
Endocrine disorders
Basedow's disease	1/777 (0.1%)
Goitre	1/777 (0.1%)
Eye disorders
Photophobia	1/777 (0.1%)
Vision blurred	1/777 (0.1%)
Visual impairment	1/777 (0.1%)
Gastrointestinal disorders
Abdominal adhesions	2/777 (0.3%)
Abdominal mass	1/777 (0.1%)
Abdominal pain	11/777 (1.4%)
Abdominal pain upper	3/777 (0.4%)
Abdominal rigidity	1/777 (0.1%)
Anal fistula	8/777 (1%)
Anal stenosis	1/777 (0.1%)
Anorectal disorder	1/777 (0.1%)
Ascites	1/777 (0.1%)
Colitis	1/777 (0.1%)
Colonic pseudo-obstruction	1/777 (0.1%)
Colonic stenosis	3/777 (0.4%)
Constipation	4/777 (0.5%)
Crohn's disease	92/777 (11.8%)
Dental caries	1/777 (0.1%)
Diarrhoea	2/777 (0.3%)
Enteritis	1/777 (0.1%)
Enterocolitis	1/777 (0.1%)
Enterocutaneous fistula	2/777 (0.3%)
Faecal volume increased	1/777 (0.1%)
Frequent bowel movements	1/777 (0.1%)
Gastritis	1/777 (0.1%)
Gastrointestinal fistula	1/777 (0.1%)
Gastrointestinal obstruction	1/777 (0.1%)
Haemorrhoids	2/777 (0.3%)
Ileal perforation	1/777 (0.1%)
Ileal stenosis	4/777 (0.5%)
Ileus	1/777 (0.1%)
Intestinal fistula	1/777 (0.1%)
Intestinal obstruction	10/777 (1.3%)
Intestinal perforation	1/777 (0.1%)
Intestinal stenosis	2/777 (0.3%)
Jejunal perforation	1/777 (0.1%)
Large intestine perforation	2/777 (0.3%)
Lower gastrointestinal haemorrhage	1/777 (0.1%)
Megacolon	1/777 (0.1%)
Mesenteric vein thrombosis	1/777 (0.1%)
Nausea	6/777 (0.8%)
Pancreatitis	2/777 (0.3%)
Pancreatitis acute	1/777 (0.1%)
Peritonitis	1/777 (0.1%)
Proctalgia	1/777 (0.1%)
Rectal haemorrhage	1/777 (0.1%)
Small intestinal obstruction	30/777 (3.9%)
Small intestinal perforation	1/777 (0.1%)
Small intestinal stenosis	1/777 (0.1%)
Small intestine ulcer	1/777 (0.1%)
Vomiting	6/777 (0.8%)
General disorders
Chest pain	1/777 (0.1%)
Chills	2/777 (0.3%)
Fatigue	1/777 (0.1%)
Feeling cold	1/777 (0.1%)
Hernia	3/777 (0.4%)
Non-cardiac chest pain	1/777 (0.1%)
Obstruction	1/777 (0.1%)
Pain	2/777 (0.3%)
Peripheral coldness	1/777 (0.1%)
Pyrexia	6/777 (0.8%)
Hepatobiliary disorders
Cholecystitis	2/777 (0.3%)
Cholelithiasis	2/777 (0.3%)
Jaundice cholestatic	1/777 (0.1%)
Immune system disorders
Hypersensitivity	1/777 (0.1%)
Infections and infestations
Abdominal abscess	5/777 (0.6%)
Abdominal sepsis	1/777 (0.1%)
Abscess	3/777 (0.4%)
Abscess intestinal	2/777 (0.3%)
Abscess limb	1/777 (0.1%)
Acute pulmonary histoplasmosis	1/777 (0.1%)
Anal abscess	15/777 (1.9%)
Appendicitis	1/777 (0.1%)
Arthritis infective	1/777 (0.1%)
Breast cellulitis	1/777 (0.1%)
Bronchitis	3/777 (0.4%)
Campylobacter infection	1/777 (0.1%)
Catheter sepsis	1/777 (0.1%)
Cellulitis	3/777 (0.4%)
Cervicitis	1/777 (0.1%)
Clostridial infection	2/777 (0.3%)
Clostridium difficile colitis	2/777 (0.3%)
Coccidioidomycosis	1/777 (0.1%)
Escherichia infection	1/777 (0.1%)
Gastroenteritis	5/777 (0.6%)
Gastroenteritis viral	3/777 (0.4%)
Herpes zoster	1/777 (0.1%)
Lobar pneumonia	3/777 (0.4%)
Lower respiratory tract infection	1/777 (0.1%)
Muscle abscess	1/777 (0.1%)
Otitis media	1/777 (0.1%)
Perineal abscess	1/777 (0.1%)
Perirectal abscess	5/777 (0.6%)
Peritonsillar abscess	1/777 (0.1%)
Pneumonia	8/777 (1%)
Pneumonia fungal	1/777 (0.1%)
Post procedural infection	2/777 (0.3%)
Pulmonary tuberculosis	1/777 (0.1%)
Pyelonephritis	5/777 (0.6%)
Rectal abscess	3/777 (0.4%)
Scrotal abscess	1/777 (0.1%)
Sepsis	4/777 (0.5%)
Septic shock	1/777 (0.1%)
Sinusitis	3/777 (0.4%)
Staphylococcal infection	1/777 (0.1%)
Urinary tract infection	3/777 (0.4%)
Viral infection	1/777 (0.1%)
Vulval abscess	1/777 (0.1%)
Injury, poisoning and procedural complications
Anastomotic ulcer	1/777 (0.1%)
Head injury	1/777 (0.1%)
Humerus fracture	1/777 (0.1%)
Incisional hernia	1/777 (0.1%)
Injury	2/777 (0.3%)
Medical device complication	1/777 (0.1%)
Multiple injuries	1/777 (0.1%)
Overdose	1/777 (0.1%)
Postoperative fever	1/777 (0.1%)
Postoperative ileus	1/777 (0.1%)
Procedural nausea	1/777 (0.1%)
Procedural pain	1/777 (0.1%)
Procedural site reaction	1/777 (0.1%)
Radius fracture	1/777 (0.1%)
Road traffic accident	1/777 (0.1%)
Vertebral injury	1/777 (0.1%)
Investigations
C-reactive protein increased	1/777 (0.1%)
Haematocrit decreased	1/777 (0.1%)
Haemoglobin decreased	1/777 (0.1%)
Red blood cell sedimentation rate increased	1/777 (0.1%)
Urogram normal	1/777 (0.1%)
Weight decreased	1/777 (0.1%)
Metabolism and nutrition disorders
Dehydration	7/777 (0.9%)
Electrolyte imbalance	1/777 (0.1%)
Hypokalaemia	2/777 (0.3%)
Iron deficiency	1/777 (0.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/777 (0.3%)
Arthritis	1/777 (0.1%)
Back pain	1/777 (0.1%)
Bone pain	1/777 (0.1%)
Bursitis	1/777 (0.1%)
Fistula	3/777 (0.4%)
Fistula discharge	1/777 (0.1%)
Intervertebral disc degeneration	1/777 (0.1%)
Joint contracture	1/777 (0.1%)
Lupus-like syndrome	1/777 (0.1%)
Muscular weakness	1/777 (0.1%)
Osteoarthritis	2/777 (0.3%)
Osteonecrosis	1/777 (0.1%)
Pain in extremity	1/777 (0.1%)
Rotator cuff syndrome	2/777 (0.3%)
Spinal column stenosis	1/777 (0.1%)
Spinal osteoarthritis	1/777 (0.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia	1/777 (0.1%)
Anal cancer	1/777 (0.1%)
Basal cell carcinoma	1/777 (0.1%)
Bladder cancer	1/777 (0.1%)
Breast cancer	2/777 (0.3%)
Bronchial carcinoma	1/777 (0.1%)
Colon cancer	1/777 (0.1%)
Glioblastoma multiforme	1/777 (0.1%)
Hepatic neoplasm malignant	1/777 (0.1%)
Lung adenocarcinoma	1/777 (0.1%)
Lymphoma	1/777 (0.1%)
Meningioma	1/777 (0.1%)
Ovarian cancer	1/777 (0.1%)
Prostate cancer	1/777 (0.1%)
Renal cell carcinoma	1/777 (0.1%)
Thyroid cancer	2/777 (0.3%)
Uterine leiomyoma	2/777 (0.3%)
Vaginal cancer recurrent	1/777 (0.1%)
Vulval cancer	1/777 (0.1%)
Nervous system disorders
Carotid artery disease	1/777 (0.1%)
Carpal tunnel syndrome	1/777 (0.1%)
Cerebrovascular accident	1/777 (0.1%)
Convulsion	2/777 (0.3%)
Demyelination	1/777 (0.1%)
Headache	2/777 (0.3%)
Hypoaesthesia	2/777 (0.3%)
Lumbar radiculopathy	1/777 (0.1%)
Neuropathy peripheral	1/777 (0.1%)
Optic neuritis	1/777 (0.1%)
Pregnancy, puerperium and perinatal conditions
Abortion of ectopic pregnancy	1/777 (0.1%)
Abortion spontaneous	3/777 (0.4%)
Ectopic pregnancy	1/777 (0.1%)
Psychiatric disorders
Anxiety	1/777 (0.1%)
Bipolar disorder	1/777 (0.1%)
Depression	5/777 (0.6%)
Drug dependence	1/777 (0.1%)
Insomnia	1/777 (0.1%)
Substance abuse	1/777 (0.1%)
Suicide attempt	1/777 (0.1%)
Renal and urinary disorders
Bladder prolapse	1/777 (0.1%)
Calculus ureteric	2/777 (0.3%)
Nephrolithiasis	6/777 (0.8%)
Renal failure acute	1/777 (0.1%)
Stress urinary incontinence	1/777 (0.1%)
Reproductive system and breast disorders
Breast enlargement	1/777 (0.1%)
Breast hyperplasia	1/777 (0.1%)
Cervical dysplasia	1/777 (0.1%)
Colpocele	1/777 (0.1%)
Cystocele	1/777 (0.1%)
Endometriosis	1/777 (0.1%)
Female genital tract fistula	1/777 (0.1%)
Menorrhagia	2/777 (0.3%)
Ovarian cyst	5/777 (0.6%)
Rectocele	1/777 (0.1%)
Uterine prolapse	1/777 (0.1%)
Vaginal prolapse	2/777 (0.3%)
Respiratory, thoracic and mediastinal disorders
Asthma	2/777 (0.3%)
Atelectasis	2/777 (0.3%)
Bronchial hyperreactivity	1/777 (0.1%)
Chronic obstructive pulmonary disease	1/777 (0.1%)
Cough	1/777 (0.1%)
Dyspnoea	1/777 (0.1%)
Nasal polyps	1/777 (0.1%)
Pleural effusion	1/777 (0.1%)
Pleurisy	1/777 (0.1%)
Pneumonia aspiration	1/777 (0.1%)
Pulmonary embolism	2/777 (0.3%)
Respiratory failure	1/777 (0.1%)
Sinus polyp	1/777 (0.1%)
Skin and subcutaneous tissue disorders
Granuloma annulare	1/777 (0.1%)
Hidradenitis	1/777 (0.1%)
Skin discolouration	1/777 (0.1%)
Social circumstances
Physical assault	1/777 (0.1%)
Surgical and medical procedures
Abortion induced	3/777 (0.4%)
Mammoplasty	1/777 (0.1%)
Medical device removal	1/777 (0.1%)
Vascular disorders
Axillary vein thrombosis	1/777 (0.1%)
Deep vein thrombosis	1/777 (0.1%)
Hypertension	1/777 (0.1%)
Hypotension	1/777 (0.1%)
Venous thrombosis	1/777 (0.1%)
Other (Not Including Serious) Adverse Events
	Open-label Adalimumab
	Affected / at Risk (%)	# Events
Total	720/777 (92.7%)
Blood and lymphatic system disorders
Anaemia	46/777 (5.9%)
Gastrointestinal disorders
Abdominal distension	65/777 (8.4%)
Abdominal pain	180/777 (23.2%)
Abdominal pain upper	45/777 (5.8%)
Abdominal tenderness	45/777 (5.8%)
Anal fistula	45/777 (5.8%)
Constipation	81/777 (10.4%)
Crohn's disease	309/777 (39.8%)
Diarrhoea	118/777 (15.2%)
Dyspepsia	64/777 (8.2%)
Flatulence	44/777 (5.7%)
Gastrooesophageal reflux disease	54/777 (6.9%)
Nausea	142/777 (18.3%)
Vomiting	82/777 (10.6%)
General disorders
Fatigue	107/777 (13.8%)
Influenza like illness	48/777 (6.2%)
Injection site irritation	46/777 (5.9%)
Injection site pain	43/777 (5.5%)
Injection site reaction	60/777 (7.7%)
Oedema peripheral	47/777 (6%)
Pain	45/777 (5.8%)
Pyrexia	105/777 (13.5%)
Infections and infestations
Bronchitis	92/777 (11.8%)
Gastroenteritis	58/777 (7.5%)
Gastroenteritis viral	42/777 (5.4%)
Influenza	137/777 (17.6%)
Nasopharyngitis	203/777 (26.1%)
Sinusitis	116/777 (14.9%)
Upper respiratory tract infection	150/777 (19.3%)
Urinary tract infection	80/777 (10.3%)
Viral infection	40/777 (5.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	192/777 (24.7%)
Back pain	87/777 (11.2%)
Fistula	40/777 (5.1%)
Muscle spasms	43/777 (5.5%)
Pain in extremity	47/777 (6%)
Nervous system disorders
Dizziness	54/777 (6.9%)
Headache	141/777 (18.1%)
Psychiatric disorders
Anxiety	54/777 (6.9%)
Depression	70/777 (9%)
Insomnia	81/777 (10.4%)
Respiratory, thoracic and mediastinal disorders
Cough	82/777 (10.6%)
Oropharyngeal pain	84/777 (10.8%)
Skin and subcutaneous tissue disorders
Eczema	52/777 (6.7%)
Pruritus	50/777 (6.4%)
Rash	100/777 (12.9%)
Vascular disorders
Hypertension	44/777 (5.7%)

Limitations/Caveats

This study was stopped by the sponsor in December 2008 when the pre-specified termination criteria were met. Subjects who continued in the study through the termination date were considered as having completed the study.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Any investigator or institution that plans on presenting/publishing results disclosure, should provide written notification to Abbott within 60 days of their presentation/publication. Abbott requests that no presentation/publication will be allowed until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay of any proposed presentation/publication maybe requested if Abbott needs to secure patent or other proprietary protection.