Study of Efficacy and Safety of Secukinumab in Japanese Patients With Active Ankylosing Spondylitis

This table is ASAS20 response using non-responder imputation for FAS

It assesses the efficacy of secukinumab 150 mg s.c. at Week 16 relative to baseline in Japanese patients with active AS based on the proportion of patients achieving an ASAS (Assessment of SpondyloArthritis International Society criteria) 20 response.

The ASAS Response Criteria (ASAS 20) is defined as an improvement of ≥ 20% and ≥ 1 unit on a scale of 10 in at least three of the four main domains and no worsening of ≥ 20% and ≥ 1 unit on a scale of 10 in the remaining domain

The efficacy of secukinumab 150 mg s.c. at Week 16 relative to baseline based on the proportion of patients achieving an ASAS 40 response

ASAS40 response is defined as an improvement of ≥40% and ≥2 units on a scale of 10 in at least three of the four ASAS main domains and no worsening at all in the remaining domain

The efficacy of secukinumab 150 mg s.c. at Week 16 relative to baseline based on the proportion of patients achieving Bath Ankylosing Spondylitis Disease Activity (BASDAI) 50 response

The BASDAI 50 is defined as an improvement of at least 50% in the BASDAI compared to baseline

hsCRP (mg/L) change from baseline using observed data with log e transformation

The efficacy of secukinumab 150 mg s.c. at Week 16 relative to baseline based on the change from baseline of high sensitivity C-Reactive Protein (hsCRP)

hsCRP is measured as a marker of inflammation from blood samples during the study

The efficacy of secukinumab 150 mg s.c. at Week 16 relative to baseline based on the proportion of patients meeting the ASAS 5/6 response criteria

The ASAS 5/6 improvement criteria is an improvement of ≥20% in at least five of all six domains

The efficacy of secukinumab 150 mg s.c. at Week 16 relative to baseline based on the change from baseline in total BASDAI

The BASDAI consists of a 0 - 10 scale measuring discomfort, pain, and fatigue (0 being no problem and 10 being the worst problem) in response to six questions asked of the patient pertaining to the five major symptoms of AS

Each question (question 1 to 6) is scored from 0 to 10 (0 being no problem and 10 being the worst problem). To give each symptom equal weighting, the mean (average) of the two scores relating to morning stiffness (questions 5 and 6) is taken. The mean of questions 5 and 6 is added to the scores from questions 1-4. The resulting 0 to 50 score is divided by 5 to give a final 0 - 10 BASDAI score.

SF-36 PCS, mean change from baseline:

The efficacy of secukinumab 150 mg s.c. at Week 16 relative to baseline based on the change from baseline in Short Form Health Survey Physical Component Summary (SF-36 PCS)

The SF-36 is an instrument to measure health-related quality of life among healthy patients and patients with acute and chronic conditions

Score range is from 0 (no problems) to 100 (unable to perform the activity)

SF-36 is a 36 item questionnaire which measures Quality of Life across eight domains, which are both physically and emotionally based. Two overall summary scores, the Physical Component Summary (PCS) and Mental Component Summary (MCS) can be computed. In this study, SF-36 PCS is used to assess improvement from baseline. There is no total overall score; scoring is computed for both subscores and summary scores. For subscores and summary scores, 0 =worst score (or quality of life) and 100=best score.

The efficacy of secukinumab 150 mg s.c. at Week 16 relative to baseline based on the change from baseline in Ankylosing Spondylitis Quality of Life (ASQoL)

The ASQoL is a self-administered questionnaire designed to assess health-related quality of life in adult patients with Ankylosing Spondylitis. The ASQoL contains 18 items with a dichotomous yes/no response option. A single point is assigned for each "yes" response and no points for each "no" response resulting in overall scores that range from 0 (least severity) to 18 (highest severity)

The efficacy of secukinumab 150 mg s.c. at Week 16 relative to baseline based on the proportion of patients achieving an ASAS partial remission

The ASAS partial remission criteria are defined as a value not above 2 units in each of the four main domains on a scale of 10

The assessment of pre dose concentration of secukinumab in Japanese AS patients

An enzyme-linked immunosorbent assay (ELISA) method will be used for bioanalytical analysis of secukinumab in serum, with an anticipated lower limit of quantification (LLOQ) of 80 ng/mL.

Concentration of anti-secukinumab antibodies

Assessment of immunogenicity against secukinumab by concentration of anti-secukinumab antibodies at pre-dose.

An electrochemiluminescence method was used for the detection of potential anti-secukinumab antibody formation.

Common Terminology Criteria for Adverse Events (CTCAE) Grades 1-5 refer to severity of the AE:

Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated.

Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL)*.

Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL**.

Grade 4 Life-threatening consequences; urgent intervention indicated.

Grade 5 Death related to AE.

*Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc.

**Self care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden.

Common Terminology Criteria for Adverse Events (CTCAE) Grades 1-5 refer to severity of the AE:

Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated.

Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL)*.

Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL**.

Grade 4 Life-threatening consequences; urgent intervention indicated.

Grade 5 Death related to AE.

*Instrumental ADL include preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc.

**Self care ADL include bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden.

During the entire safety reporting period, mean values of each liver enzyme parameter stayed within the normal range and were comparable to the baseline values

ALP=Alkaline phosphatase ALT=Alanine aminotransferase AST=Aspartate aminotransferase TBL=Total bilirubin ULN=Upper Limit Normal

During the entire safety reporting period, mean values of each lipid parameter stayed within the normal range and were comparable to the baseline values

Sitting Pulse (bpm) High only (> 100 bpm) Low only (< 60 bpm) Low and High (< 60 bpm and > 100 bpm)

Sitting Diastolic Blood Pressure (BP) (mmHg) High only (≥ 90 mmHg) Low only (< 60 mmHg) Low and High (< 60 mmHg and ≥ 90 mmHg)

Sitting Systolic Blood Pressure (mmHg) High only (≥ 140 mmHg) Low only (< 90 mmHg) Low and High (< 90 mmHg and ≥ 140 mmHg)