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).

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).

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.

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.

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).

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.

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).

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).

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).

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