Efficacy and Safety Study of Secukinumab in Chinese Participants With Non-radiographic Axial Spondyloarthritis

ASAS40 response was defined as relative improvement of at least 40% and absolute improvement of at least 2 units on a 0 to 10 scale in at least 3 of the 4 main domains of the ASAS and no worsening at all in the remaining domain.

The 4 main domains of the ASAS are: 1.Patient's Global Assessment of Disease Activity (score ranged from 0 [not active] to 10 [very active]); 2.Back Pain (score ranged from 0 [no pain] to 10 [severe pain]); 3.Function (Bath Ankylosing Spondylitis Functional Index [BASFI]) (score ranged from 0 [easy] to 10 [impossible]); 4.Inflammation (mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions 5 and 6 concerning morning stiffness intensity and duration) (score ranged from 0 [none] to 10 [very severe]).

The percentage of TNF-alpha-inhibitor-naïve participants who achieved ASAS40 response at Week 16 was assessed using a logistic regression model. Discontinued participants and those with missing responses were considered non-responders

ASAS40 response was defined as relative improvement of at least 40% and absolute improvement of at least 2 units on a 0 to 10 scale in at least 3 of the 4 main domains of the ASAS and no worsening at all in the remaining domain.

The 4 main domains of the ASAS are: 1.Patient's Global Assessment of Disease Activity (score ranged from 0 [not active] to 10 [very active]); 2.Back Pain (score ranged from 0 [no pain] to 10 [severe pain]); 3.Function (BASFI) (score ranged from 0 [easy] to 10 [impossible]); 4.Inflammation (mean of BASDAI questions 5 and 6 concerning morning stiffness intensity and duration) (score ranged from 0 [none] to 10 [very severe]).

The percentage of participants who achieved ASAS40 response at Week 16 was assessed using a logistic regression model. Discontinued participants and those with missing responses were considered non-responders

The ASAS 5/6 response was defined as an improvement of ≥20% in at least five of all six domains of the ASAS: 1.Patient's Global Assessment of Disease Activity (score ranged from 0 [not active] to 10 [very active]); 2.Back Pain (score ranged from 0 [no pain] to 10 [severe pain]); 3.Function (BASFI) (score ranged from 0 [easy] to 10 [impossible]); 4.Inflammation (mean of BASDAI questions 5 and 6 concerning morning stiffness intensity and duration) (score ranged from 0 [none] to 10 [very severe]); 5) spinal mobility represented by the BAS Disease Metrology Index (BASDMI) (scale ranged from 0 [no limitation of movement] to 10 [very severe limitation of movement]; and 6) C-reactive protein (acute phase reactant).

The percentage of participants who achieved ASAS 5/6 response at Week 16 was assessed using a logistic regression model. Missing responses were imputed as non-responders. Discontinued participants were considered non-responders

The BASDAI consisted of a 0 through 10 scale (0 being no problem and 10 being the worst problem, captured as a continuous VAS), which was used to answer 6 questions pertaining to the 5 major symptoms of AS: 1. Fatigue; 2. Spinal pain; 3. Joint pain / swelling; 4. Areas of localized tenderness (called enthesitis, or inflammation of tendons and ligaments); 5. Morning stiffness duration; 6. Morning stiffness severity. BASDAI score was calculated as the mean of the questions 5 and 6. The resulting 0 to 10 score was added to the scores from questions 1-4. The resulting 0 to 50 score was divided by 5 to give a final 0-10 BASDAI score, where higher score indicated high disease activity.

The change from baseline in BASDAI scores at Week 16 was assessed using Mixed-effects model repeated measures (MMRM). A negative change from baseline indicated improvement.

The BASDAI consisted of a 0 through 10 scale (0 being no problem and 10 being the worst problem, captured as a continuous VAS), which was used to answer 6 questions pertaining to the 5 major symptoms of AS: 1. Fatigue; 2. Spinal pain; 3. Joint pain / swelling; 4. Areas of localized tenderness (called enthesitis, or inflammation of tendons and ligaments); 5. Morning stiffness duration; 6. Morning stiffness severity. BASDAI score was calculated as the mean of the questions 5 and 6. The resulting 0 to 10 score was added to the scores from questions 1-4. The resulting 0 to 50 score was divided by 5 to give a final 0-10 BASDAI score, where higher score indicated high disease activity. BASDAI 50 was defined as an improvement of at least 50% in the BASDAI total score compared to baseline.

The percentage of participants achieving BASDAI 50 at Week 16 was assessed using a logistic regression model. Discontinued participants and with missing responses were considered non-responders

hsCRP was measured as a marker of inflammation from blood samples. The change from baseline in hsCRP at Week 16 was assessed using MMRM. It was expressed as a ratio of Week 16 to baseline values. Ratios less than 1.0 at Week 16 represented reduced hsCRP.

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, with higher scores indicating a higher degree of functional limitation in patients. The change from baseline in BASFI at Week 16 was assessed. A negative change from baseline indicated improvement.

The MRI assessment of the total edema score of the Sacroiliac Joint (SIJ) measured the degree of edema or fluid accumulation in the joint. The score ranged from 0 to 24, with higher scores indicating more severe inflammation. The change from baseline in inflammation, as measured by the SI joint total edema score at Week 16, was evaluated using an ANCOVA model. Any missing data was imputed using multiple imputation prior to running the ANCOVA analysis.

ASAS20 response was defined as relative improvement of at least 20% and absolute improvement of at least 1 unit on a 0 to 10 scale in at least 3 of the 4 main domains of the ASAS and no worsening of ≥20% and ≥1 unit at all in the remaining domain.

The 4 main domains of ASAS are 1.Patient's Global Assessment of Disease Activity (score ranged from 0 [not active] to 10 [very active]); 2.Back Pain (score ranged from 0 [no pain] to 10 [severe pain]); 3.Function (BASFI) (score ranged from 0 [easy] to 10 [impossible]); 4.Inflammation (mean of BASDAI questions 5 and 6 concerning morning stiffness intensity and duration) (score ranged from 0 [none] to 10 [very severe]) The percentage of participants who achieved ASAS20 response at Week 16 was assessed using a logistic regression model. Discontinued participants and those with missing responses were considered non-responders

SF-36 was an instrument used to measure health-related quality of life among healthy patients and patients with acute and chronic conditions. It consisted of eight subscales (domains) that could be scored individually: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role- Emotional, and Mental Health. Each domain score ranged from 0 to 100, with higher scores indicating a higher level of functioning. The Physical Component Summary (PCS) was an overall summary score calculated from the 8 domains. It was a norm-based score with a mean of 50 and a standard deviation of 10. Higher scores indicated a higher level of functioning.

The change from baseline in PCS at Week 16 was evaluated using MMRM. A positive change from baseline indicated an improvement.

The ASQoL was a self-administered questionnaire designed to assess health-related quality of life (HRQoL) in participants with ankylosing spondylitis. The ASQoL contained 18 items with a dichotomous yes/no response option. A single point was assigned for each "yes" response and no points for each "no" response resulting in overall scores that ranged from 0 (least severity) to 18 (highest severity). As such, a lower score indicated a better quality of life. Items included an assessment of mobility/energy, self-care, and mood/emotion.

The change from baseline in ASQoL at Week 16 was assessed using MMRM. A negative change from baseline indicated an improvement.

The ASAS partial remission criteria were defined as a value not above 2 units (on a scale of 10) in each of the 4 main ASAS domains: 1. Patient's Global Assessment of Disease Activity (score ranged from 0 [not active] to 10 [very active]); 2. Back Pain (assessed on a scale of 0 [no pain] to 10 [severe pain]); 3. Function (BASFI) (score ranged from 0 [easy] to 10 [impossible]); 4. Inflammation (mean of BASDAI questions 5 and 6 concerning morning stiffness intensity and duration) (score ranged from 0 [none] to 10 [very severe]).

The percentage of participants who achieved ASAS partial remission response at Week 16 was assessed using a logistic regression model. Missing responses were imputed as non-responders. Discontinued participants were considered non-responders.