Study to Demonstrate the Efficacy, Safety and Tolerability of an Intravenous Regimen of Secukinumab Compared to Placebo in Subjects With Active axSpA

ASDAS-CRP was utilized to assess disease activity status. Parameters used for the ASDAS included: total back pain (BASDAI question 2), patient's global assessment of disease activity, peripheral pain/swelling (BASDAI question 3), duration of morning stiffness (BASDAI question 6) and CRP in mg/L. Disease activity states: inactive disease, moderate disease activity, high disease activity, and very high disease activity. The three values selected to separate these states are: < 1.3 between inactive disease and moderate disease activity; < 2.1 between moderate disease activity and high disease activity; and > 3.5 between high disease activity and very high disease activity. Selected cutoffs for improvement scores are a change of ≥ 1.1 unit for "minimal clinically important improvement" and a change of ≥ 2.0 units for "major improvement" .

BASDAI consists of a 0 through 10 scale (0 indicating no problem and 10 indicating the worst problem, captured as a continuous VAS), which was used to answer six questions pertaining to the five major symptoms of AS: fatigue, spinal pain, peripheral joint pain / swelling,, areas of localized tenderness (enthesitis, or inflammation of tendons and ligaments), morning stiffness duration, morning stiffness severity.

To give each symptom equal weight, the mean of the two scores relating to morning stiffness is taken into account (questions 5 and 6). The resulting 0 to 10 score is added to the scores for questions 1 through 4. The resulting 0 to 50 score is divided by 5 to give a final 0 10 BASDAI score.

The ASAS 5/6 improvement criteria is an improvement of ≥20% in at least five of all six domains. A higher score on the VAS signifies higher severity.

ASAS consists of 6 domains (4 main and 2 additional): 1. Patient's global assessment measured on a visual analog scale (VAS); 2. Patient's assessment of back pain, measured on a VAS; 3. Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) measured by VAS; 4. Inflammation represented by mean duration and severity of morning stiffness, on the BAS Disease Activity Index (BASDAI) as measured by VAS; 5. Spinal mobility represented by the BAS Metrology Index (BASMI) lateral spinal flexion assessment; 6. C-reactive protein (acute phase reactant).

The BASFI is a set of 10 questions designed to determine the degree of functional limitation in subjects with AS. The questions were chosen on the basis of predominant input from subjects with AS. The first eight questions consider activities related to functional anatomy. The final two questions assess the subjects' ability to cope with everyday life. A 0-10 scale (captured as a continuous VAS) is used to answer the questions. The BASFI score is the mean of the ten scales - a value between 0 and 10.

The Short Form-36 Physical Component Summary (SF-36 PCS) is an instrument to measure health-related quality of life among healthy patients and patients with acute and chronic conditions.

It consists of eight subscales (domains) that can be scored individually: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role- Emotional, and Mental Health. Two overall summary scores, the Physical Component Summary (PCS) and the Mental Component Summary (MCS) also can be computed. The eight domains are based on a scale from 0-100 while PCS and MCS are norm-based scores with a mean of 50 and a standard deviation of 10.

Higher scores indicate a higher level of functioning. A positive change from baseline score indicates an improvement.

The ASQoL is a self-administered questionnaire designed to assess health-related quality of life in adult subjects with AS. 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). As such, lower scores indicate better quality of life. Items include an assessment of mobility/energy, self care and mood/emotion. The recall period is "at the moment".

This assessment (laboratory assessment) was performed in order to identify the presence of inflammation, to determine its severity and to monitor the response to treatment. Exponentially transformed LSM, the geometric mean ratio of post-baseline/baseline. A value <1 indicates a reduced CRP

The ASAS Response Criteria (ASAS20) 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. A higher score on the VAS signifies higher severity.

ASAS consists of 6 domains (4 main and 2 additional): 1. Patient's global assessment measured on a visual analog scale (VAS); 2. Patient's assessment of back pain, measured on a VAS; 3. Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) measured by VAS; 4. Inflammation represented by mean duration and severity of morning stiffness, on the BAS Disease Activity Index (BASDAI) as measured by VAS; 5. Spinal mobility represented by the BAS Metrology Index (BASMI) lateral spinal flexion assessment; 6. C-reactive protein (acute phase reactant).

ASDAS-CRP was utilized to assess disease activity status. Parameters used for the ASDAS included: total back pain (BASDAI question 2), patient's global assessment of disease activity, peripheral pain/swelling (BASDAI question 3), duration of morning stiffness (BASDAI question 6) and CRP in mg/L.

Disease activity states: inactive disease, moderate disease activity, high disease activity, and very high disease activity. The three values selected to separate these states are: < 1.3 between inactive disease and moderate disease activity; < 2.1 between moderate disease activity and high disease activity; and > 3.5 between high disease activity and very high disease activity. Selected cutoffs for improvement scores are a change of ≥ 1.1 unit for "minimal clinically important improvement" and a change of ≥ 2.0 units for "major improvement"

ASAS partial remission criteria are defined as a value not above 2 units in each of the four main ASAS domains on a scale of 0-10.

ASAS consists of 6 domains (4 main and 2 additional): 1. Patient's global assessment measured on a visual analog scale (VAS); 2. Patient's assessment of back pain, measured on a VAS; 3. Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) measured by VAS; 4. Inflammation represented by mean duration and severity of morning stiffness, on the BAS Disease Activity Index (BASDAI) as measured by VAS; 5. Spinal mobility represented by the BAS Metrology Index (BASMI) lateral spinal flexion assessment; 6. C-reactive protein (acute phase reactant).

The PSQI is a self-report questionnaire that assesses sleep quality over a 1-month time interval. Consisting of 19 items, the PSQI measures several different aspects of sleep, offering seven component scores and one composite score. The component scores consist of subjective sleep quality, sleep latency (i.e., how long it takes to fall asleep), sleep duration, habitual sleep efficiency (i.e., the percentage of time in bed that one is asleep), sleep disturbances, use of sleeping medication, and daytime dysfunction.

Each item is weighted on a 0-3 interval scale. The global PSQI score is then calculated by totaling the seven component scores, providing an overall score ranging from 0 to 21, where lower scores denoted a healthier sleep quality.