A Study of Adalimumab in Japanese Subjects With Intestinal Behçet's Disease

Marked improvement is defined as the combination of both global assessment of gastrointestinal (GI) symptoms and endoscopic improvement grades of ≤1. Global assessment of GI symptoms is a participant-assessed, investigator-confirmed grading of global symptoms from 0 to 4: 0=free of symptoms; 1=symptoms existed in past 2 weeks but did not affect participant's daily life; 2=symptoms existed in past 2 weeks and slightly affected participant's daily life; 3=symptoms existed in past 2 weeks and affected participant's daily life; 4=symptoms existed in past 2 weeks and critically affected participant's daily life. Endoscopic improvement was assessed in 4 grades compared to the screening endoscopy based on the longest diameter (none, ≥1 cm to \<2 cm, ≥2 cm to \<3 cm, ≥3 cm) of ileocecal largest open ulcer (area of mucosal defect). Grades are: 0=healing; 1=marked reduction (reduction to ≤1/4); 2=reduction (reduction to ≤1/2 - 1/4); 3=no change or worse (reduction less than 1/2 or expansion).

Time frame: 24 weeks

Population: Full analysis set (all participants). Those with missing evaluations were imputed as non-responders.

Inflammatory Bowel Disease Questionnaire (IBDQ) is the standard questionnaire to assess the quality of life of patients with inflammatory bowel disease. The IBDQ is a 32-item questionnaire consisting of 4 dimensions: bowel-related symptoms, systemic function, social function and emotional status. The responses to each question within each domain range from 1 (significant impairment) to 7 (no impairment), with total score ranging from 32 (very poor) to 224 (perfect health-related quality of life).

Time frame: Baseline, 24 weeks, 52 weeks

Population: Full analysis set (all participants). Those with missing evaluations were imputed by last observation carried forward.

The Short-Form-36 (SF-36) Health Survey is a comprehensive quality of life scale. An increase in SF-36 score indicates alleviation of the disease and a decrease in score indicates aggravation of disease. The physical component reflects activity level, activity limitations, pain and rating of one's health. Score on the physical component ranges from 0 (poorest health) to 100 (best health). The mental component reflects vitality, social functioning, role-emotional and mental health. Score on the mental component ranges from 0 (poorest health) to 100 (best health).

Time frame: Baseline, 24 weeks, 52 weeks

Population: Full analysis set (all participants). Those with missing evaluations were imputed by last observation carried forward.

C-Reactive Protein (CRP) normal range was defined as ≤0.3 mg/dL.

Time frame: Baseline, 24 weeks, 52 weeks

Population: Full analysis set (all participants). Those with missing evaluations were imputed by last observation carried forward.

Participants assessed their abdominal pain, diarrhea and other gastrointestinal symptoms (abdominal discomfort, abdominal fullness, etc) during 2 weeks before assessment visit in 5 grades. Investigator confirmed the assessment through interview with participants. Assessment is graded from 0 to 4: 0=free of symptoms; 1=symptoms existed in past 2 weeks but did not affect participant's daily life; 2=symptoms existed in past 2 weeks and slightly affected participant's daily life; 3=symptoms existed in past 2 weeks and affected participant's daily life; 4=symptoms existed in past 2 weeks and critically affected participant's daily life. Improvement of ≥1 grade from baseline is also presented.

Time frame: 24 weeks, 52 weeks

Population: Full analysis set (all participants). n=number of participants who had any symptom at baseline. Those with missing evaluations were imputed as non-responders.

Study participants completed a global assessment of their gastrointestinal symptoms (Behçet's disease symptoms other than gastrointestinal symptoms were excluded) during 2 weeks before assessment visit on a 5-grade scale. The investigator confirmed this assessment via interview with participants. Assessment is graded from 0 to 4: 0=free of symptoms; 1=symptoms existed in past 2 weeks but did not affect participant's daily life; 2=symptoms existed in past 2 weeks and slightly affected participant's daily life; 3=symptoms existed in past 2 weeks and affected participant's daily life; 4=symptoms existed in past 2 weeks and critically affected participant's daily life. Global assessment of grade 0 or ≤1 and improvement of ≥1 (from baseline) is presented.

Time frame: 24 weeks, 52 weeks

Population: Full analysis set (all participants). Those with missing evaluations were imputed as non-responders.

Complete remission was defined as both endoscopic improvement and global assessment of gastrointestinal symptoms grades of 0. Endoscopic improvement was assessed in 4 grades compared to the screening (baseline) endoscopy based on the longest diameter (none, ≥1 cm to \<2 cm, ≥2 cm to \<3 cm, ≥3 cm) of ileocecal largest open ulcer (area of mucosal defect). Grades are: 0=healing; 1=marked reduction (reduction to ≤1/4); 2=reduction (reduction to ≤1/2 - 1/4); 3=no change or worse (reduction less than 1/2 or expansion). Global assessment of gastrointestinal symptoms is a participant-assessed, investigator-confirmed grading of global symptoms from 0 to 4: 0=free of symptoms; 1=symptoms existed in past 2 weeks but did not affect participant's daily life; 2=symptoms existed in past 2 weeks and slightly affected participant's daily life; 3=symptoms existed in past 2 weeks and affected participant's daily life; 4=symptoms existed in past 2 weeks and critically affected participant's daily life.

Time frame: 24 weeks, 52 weeks

Population: Full analysis set (all participants). Those with missing evaluations were imputed as non-responders.

Endoscopic improvement was assessed in 4 grades compared to the screening (baseline) endoscopy based on the longest diameter (none, ≥1 cm to \<2 cm, ≥2 cm to \<3 cm, ≥3 cm) of ileocecal largest open ulcer (area of mucosal defect). Grades are: 0=healing; 1=marked reduction (reduction to ≤1/4); 2=reduction (reduction to ≤1/2 - 1/4); 3=no change or worse (reduction less than 1/2 or expansion).

Time frame: 24 weeks, 52 weeks

Population: Full analysis set (all participants). Those with missing evaluations were imputed as non-responders.

Marked improvement is defined as the combination of both global assessment of gastrointestinal (GI) symptoms and endoscopic improvement grades of ≤1. Global assessment of GI symptoms is a participant-assessed, investigator-confirmed grading of global symptoms from 0 to 4: 0=free of symptoms; 1=symptoms existed in past 2 weeks but did not affect participant's daily life; 2=symptoms existed in past 2 weeks and slightly affected participant's daily life; 3=symptoms existed in past 2 weeks and affected participant's daily life; 4=symptoms existed in past 2 weeks and critically affected participant's daily life. Endoscopic improvement was assessed in 4 grades compared to the screening endoscopy based on the longest diameter (none, ≥1 cm to \<2 cm, ≥2 cm to \<3 cm, ≥3 cm) of ileocecal largest open ulcer (area of mucosal defect). Grades are: 0=healing; 1=marked reduction (reduction to ≤1/4); 2=reduction (reduction to ≤1/2 - 1/4); 3=no change or worse (reduction less than 1/2 or expansion).

Time frame: 52 weeks

Population: Full analysis set (all participants). Those with missing evaluations were imputed as non-responders.

Investigators assessed oral aphthous (mouth ulcers), skin symptoms, eye symptoms and vulval (genital) ulcers during 4 weeks before study visit via participant interview, using the following grades. Oral aphthous: 0=None; 1=Symptom existed less than 2 weeks in recent 4 weeks; 2=Symptom existed 2 weeks or more in recent 4 weeks; 3=Symptom existed mostly in recent 4 weeks. Skin (Erythema nodosum rash): 0=None; 1=Symptom existed less than 2 weeks in recent 4 weeks; 2=Symptom existed 2 weeks or more in recent 4 weeks; 3=Symptom existed mostly in recent 4 weeks. Eye (Uveitis): 0=None; 1=one eye crisis in recent 4 weeks; 2=two eye crises in recent 4 weeks; 3=three eye crises in recent 4 weeks. Vulval (genital) ulcer: 0=None; 1=Symptom existed less than 2 weeks in recent 4 weeks; 2=Symptom existed 2 weeks or more in recent 4 weeks; 3=Symptom existed mostly in recent 4 weeks. Resolution was defined as: Behçet's disease symptoms other than gastrointestinal symptoms were graded 0 (disappeared).

Time frame: 24 weeks, 52 weeks

Population: Full analysis set (all participants). n=number of participants who had any symptom at baseline. Those with missing evaluations were imputed as non-responders.