Trial Outcomes & Findings for Effects of Adalimumab on Mucosal Healing in Subjects With Crohn's Disease Involving the Colon (NCT NCT00348283)

Last Updated: 2011-04-11

Results Overview

Subjects were to have undergone up to 4 endoscopies to evaluate the presence or absence of mucosal ulceration: at Screening, at Week 12 (subjects who moved to open label (OL) drug between Week 8 and Week 12 because of disease flare or non-response were evaluated by endoscopy prior to receiving OL dosing), at the time of switch from blinded study drug to OL adalimumab at any time after Week 12, and at Week 52 or Early Termination. Subjects who remained blinded for the entire 52-week trial or switched to OL adalimumab between Week 8 and Week 12 were to have undergone 3 endoscopies.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

135 participants

Primary outcome timeframe

Week 12

Results posted on

2011-04-11

Participant Flow

Subjects were to be enrolled in 9 countries. Subjects were enrolled at 19 sites in 8 countries. No subjects were enrolled in Sweden.

All subjects (135 subjects) enrolled in the study received an open-label dose of 160 mg adalimumab subcutaneously (SC) at Baseline (Week 0) followed by 80 mg adalimumab SC at Week 2 (induction dose). At Week 4, subjects were randomized to either adalimumab 40 mg SC every other week (eow) or placebo SC eow(129 subjects).

Participant milestones

Participant milestones
Measure	Placebo SC dosing eow	Adalimumab 40 mg SC eow
Induction STARTED	0	135
Induction COMPLETED	0	129
Induction NOT COMPLETED	0	6
Double Blind STARTED	65	64
Double Blind COMPLETED	60	54
Double Blind NOT COMPLETED	5	10
Open Label STARTED	0	100
Open Label COMPLETED	0	66
Open Label NOT COMPLETED	0	34

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo SC dosing eow	Adalimumab 40 mg SC eow
Induction Adverse Event	0	2
Induction Protocol Violation	0	4
Double Blind Adverse Event	2	5
Double Blind Withdrawal by Subject	1	1
Double Blind Protocol Violation	0	1
Double Blind Lack of Efficacy	2	2
Double Blind Pregnancy	0	1
Open Label Adverse Event	0	8
Open Label Withdrawal by Subject	0	4
Open Label Lost to Follow-up	0	1
Open Label Lack of Efficacy	0	13
Open Label Administrative reasons	0	5
Open Label Subject moved to the United States	0	1
Open Label Pregnancy	0	1
Open Label Sponsor decision	0	1

Baseline Characteristics

Effects of Adalimumab on Mucosal Healing in Subjects With Crohn's Disease Involving the Colon

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=65 Participants At Baseline (Week 0), subjects received an OL dose of 160 mg adalimumab SC followed by an OL dose of 80 mg adalimumab SC at Week 2 (induction dose). At Week 4, subjects were randomized to either adalimumab 40 mg SC eow or placebo SC eow.	Adalimumab 40 mg Every Other Week n=64 Participants At Baseline (Week 0), subjects received an OL dose of 160 mg adalimumab SC followed by an OL dose of 80 mg adalimumab SC at Week 2 (induction dose). At Week 4, subjects were randomized to either adalimumab 40 mg SC eow or placebo SC eow.	Total n=129 Participants Total of all reporting groups
Age, Categorical <=18 years	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	63 Participants n=5 Participants	62 Participants n=7 Participants	125 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Age Continuous	37.2 years STANDARD_DEVIATION 12.60 • n=5 Participants	37.1 years STANDARD_DEVIATION 11.10 • n=7 Participants	37.1 years STANDARD_DEVIATION 11.84 • n=5 Participants
Sex: Female, Male Female	41 Participants n=5 Participants	40 Participants n=7 Participants	81 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants	24 Participants n=7 Participants	48 Participants n=5 Participants
Region of Enrollment France	3 participants n=5 Participants	3 participants n=7 Participants	6 participants n=5 Participants
Region of Enrollment United States	20 participants n=5 Participants	12 participants n=7 Participants	32 participants n=5 Participants
Region of Enrollment Canada	22 participants n=5 Participants	18 participants n=7 Participants	40 participants n=5 Participants
Region of Enrollment Belgium	14 participants n=5 Participants	25 participants n=7 Participants	39 participants n=5 Participants
Region of Enrollment Austria	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants
Region of Enrollment Netherlands	1 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment Germany	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Region of Enrollment Italy	2 participants n=5 Participants	3 participants n=7 Participants	5 participants n=5 Participants

PRIMARY outcome

Timeframe: Week 12

Population: Analysis was on ITT subjects with mucosal ulceration at Screening. Subjects who did not have endoscopy at Week 12 were considered to have mucosal ulceration at Week 12 (NRI). If subjects had endoscopy at Week 8, the endoscopy results from Week 8 were carried forward to Week 12 for the primary efficacy analysis.

Outcome measures

Outcome measures
Measure	Placebo n=61 Participants	Adalimumab n=62 Participants 40 mg every other week
Number of Subjects Without Mucosal Ulceration at Week 12	8 Subjects	17 Subjects

SECONDARY outcome

Timeframe: Week 12

Population: ITT set. NRI method was used to impute the missing values.

Clinical remission is defined as a CDAI less than 150. A lower score correlates with less severe Crohn's disease activity. The CDAI range for this study was 0 to 961.

Outcome measures

Outcome measures
Measure	Placebo n=65 Participants	Adalimumab n=64 Participants 40 mg every other week
Number of Subjects With Clinical Remission Crohn's Disease Activity Index (CDAI) < 150 at Week 12	18 Subjects	30 Subjects

SECONDARY outcome

Timeframe: Week 52

Population: The secondary efficacy analysis included the ITT subjects who had mucosal ulceration at screening. NRI method was used to impute the missing values.

The number of subjects receiving blinded study drug in each treatment group who were without mucosal ulceration at Week 52.

Outcome measures

Outcome measures
Measure	Placebo n=61 Participants	Adalimumab n=62 Participants 40 mg every other week
Number of Subjects Without Mucosal Ulceration at Week 52	0 Subjects	15 Subjects

SECONDARY outcome

Timeframe: Week 52

Population: ITT set. NRI method was used to impute the missing values.

Clinical remission is defined as a Crohn's Disease Activity Index (CDAI) less than 150. A lower score correlates with less severe Crohn's disease activity. The CDAI range for this study was 0 to 961.

Outcome measures

Outcome measures
Measure	Placebo n=65 Participants	Adalimumab n=64 Participants 40 mg every other week
Number of Subjects With Clinical Remission (CDAI < 150) at Week 52	6 Subjects	21 Subjects

SECONDARY outcome

Timeframe: Weeks 12 and 52

Population: Analysis was on ITT subjects who completed the Double Blind period and had Week 52 evaluations while in the Double Blind period. NRI method was used to impute the missing values.

The number of subjects receiving blinded study drug in each treatment group who were without mucosal ulceration at both Week 12 and Week 52.

Outcome measures

Outcome measures
Measure	Placebo n=11 Participants	Adalimumab n=25 Participants 40 mg every other week
Number of Subjects Without Mucosal Ulceration at Both Week 12 and Week 52	0 Subjects	7 Subjects

SECONDARY outcome

Timeframe: Weeks 12 and 52

Population: ITT set. NRI method was used to impute the missing values.

Clinical remission is defined as a Crohn's Disease Activity Index (CDAI) less than 150. A lower score correlates with less severe Crohn's disease activity. The CDAI range for this study was 0 to 961.

Outcome measures

Outcome measures
Measure	Placebo n=65 Participants	Adalimumab n=64 Participants 40 mg every other week
Number of Subjects With Clinical Remission (CDAI < 150) at Both Week 12 and Week 52	3 Subjects	19 Subjects

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 43 other events

Deaths: 0 deaths

Adalimumab

Serious events: 20 serious events

Other events: 49 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Information Specialist

Abbott

Phone: 800-633-9110

Results disclosure agreements

Principal investigator is a sponsor employee Provide ABBOTT at least sixty (60) days prior to submission for review, ABBOTT shall return within sixty (60) days. Proposed draft shall be delayed an additional sixty (60) days in addition to the Review Period
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=65 participants at risk	Adalimumab n=64 participants at risk；n=135 participants at risk All subjects (135 subjects) enrolled in the study received adalimumab 160 mg at Baseline followed by adalimumab 80 mg at Week 2 (Induction dose).
Cardiac disorders Coronary artery disease	— 0/0 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.	0.74% 1/135 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.
Gastrointestinal disorders Crohn's disease	— 0/0 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.	5.9% 8/135 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.
Gastrointestinal disorders Ileal stenosis	— 0/0 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.	0.74% 1/135 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.
Gastrointestinal disorders Intestinal fistula	— 0/0 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.	0.74% 1/135 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.
Immune system disorders Type IV hypersensitivity reaction	— 0/0 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.	0.74% 1/135 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.
Infections and infestations Anal abscess	— 0/0 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.	0.74% 1/135 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.
Infections and infestations Herpes zoster	— 0/0 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.	0.74% 1/135 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.
Infections and infestations Perianal abscess	— 0/0 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.	0.74% 1/135 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.
Infections and infestations Tonsillitis	— 0/0 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.	0.74% 1/135 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.
Infections and infestations Vulval abscess	— 0/0 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.	0.74% 1/135 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.
Injury, poisoning and procedural complications Traumatic brain injury	— 0/0 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.	0.74% 1/135 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.
Investigations Clostridium difficile toxin test positive	— 0/0 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.	0.74% 1/135 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.
Musculoskeletal and connective tissue disorders Fibromyalgia	— 0/0 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.	0.74% 1/135 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.
Reproductive system and breast disorders Ovarian cyst torsion	— 0/0 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.	0.74% 1/135 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.
Vascular disorders Deep vein thrombosis	— 0/0 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.	0.74% 1/135 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.
Vascular disorders Infarction	— 0/0 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.	0.74% 1/135 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.

Measure	Placebo n=65 participants at risk	Adalimumab n=64 participants at risk；n=135 participants at risk All subjects (135 subjects) enrolled in the study received adalimumab 160 mg at Baseline followed by adalimumab 80 mg at Week 2 (Induction dose).
Gastrointestinal disorders Abdominal distension	6.2% 4/65 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.	6.2% 4/64 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.
Gastrointestinal disorders Abdominal pain	9.2% 6/65 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.	12.5% 8/64 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.
Gastrointestinal disorders Constipation	0.00% 0/65 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.	6.2% 4/64 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.
Gastrointestinal disorders Crohn's disease	29.2% 19/65 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.	23.4% 15/64 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.
Gastrointestinal disorders Flatulence	1.5% 1/65 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.	7.8% 5/64 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.
Gastrointestinal disorders Nausea	4.6% 3/65 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.	7.8% 5/64 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.
General disorders Fatigue	3.1% 2/65 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.	10.9% 7/64 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.
General disorders Influenza like illness	4.6% 3/65 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.	9.4% 6/64 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.
General disorders Pyrexia	6.2% 4/65 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.	3.1% 2/64 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.
Infections and infestations Gastroenteritis	1.5% 1/65 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.	6.2% 4/64 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.
Infections and infestations Influenza	3.1% 2/65 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.	6.2% 4/64 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.
Infections and infestations Nasopharyngitis	12.3% 8/65 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.	14.1% 9/64 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.
Infections and infestations Sinusitis	6.2% 4/65 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.	1.6% 1/64 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.
Infections and infestations Upper respiratory tract infection	4.6% 3/65 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.	7.8% 5/64 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.
Infections and infestations Urinary tract infection	0.00% 0/65 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.	6.2% 4/64 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.
Musculoskeletal and connective tissue disorders Arthralgia	6.2% 4/65 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.	10.9% 7/64 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.
Nervous system disorders Headache	9.2% 6/65 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.	14.1% 9/64 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	4.6% 3/65 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.	6.2% 4/64 Serious adverse events were not assessed for placebo subjects (Total at risk = 0) as all subjects received an OL dose of 160 mg adalimumab at Week 0 followed by an OL induction dose of 80 mg adalimumab at Week 2.