Effect of Secukinumab on Radiographic Progression in Ankylosing Spondylitis as Compared to GP2017 (Adalimumab Biosimilar)

Radiographic progression was based on scores from the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). The mSASSS is the sum of scores assessing the vertebral corners of the lumbar and cervical spine as 0 (normal), 1 (erosion, sclerosis, or squaring), 2 (syndesmophyte), or 3 (bridging syndesmophyte) with a total range from 0-72. No radiographic progression was defined as the change from baseline in mSASSS score <= 0.5.

Radiographic changes in the spine were based on the change in score of the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) from baseline to Week 104.

The mSASSS is the sum of scores assessing the vertebral corners of the lumbar and cervical spine as 0 (normal), 1 (erosion, sclerosis, or squaring), 2 (syndesmophyte), or 3 (bridging syndesmophyte) with a total range from 0-72.

Syndesmophytes are bony growths that develop on corner of the vertebrae of the spine which are indicators of AS. A participant was considered to have a syndesmophyte if at least one reader assessed vertebral corner as >= 2 at on the mSASSS scale at baseline. Only participants with a syndesmophyte at baseline were evaluated at Week 104 for new syndesmophytes. A new syndesmophyte was a syndesmophyte present at Week 104 which was not present at baseline. Absence of new syndesmophyte was defined as having individual vertebral score < 2 on the mSASSS scale for all interpretable locations that had no syndesmophyte at baseline. Missing responses for subjects without new syndesmophyte at Week 104 were imputed by multiple imputation (MCMC).

Magnetic Resonance Images (MRI) of the Sacroiliac Joint (SIJ) were assessed for the presence and severity of SIJ bone marrow edema according to the Berlin Active Inflammatory Lesions Scoring with a minimum score of 0 and a maximum score of 24. Higher scores indicate more inflammation.

Magnetic Resonance Images (MRI) of the spine were assessed for the presence and severity of bone marrow edema in the spinal vertebrae according to the Berlin modification of the ASspiMRI-a edema score with a score range of 0 to 69. Higher scores indicate more inflammation.

Assessment of SpondyloArthritis International Society criteria (ASAS) consist of 4 domains measured on visual analog scales (VAS): 1. Patient's global assessment; 2. Patient's assessment of back pain; 3. Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) average of 10 questions; 4. Inflammation represented by mean duration and severity of morning stiffness, on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). ASAS 20 response 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.

Assessment of SpondyloArthritis International Society criteria (ASAS) consist of 4 domains measured on visual analog scales (VAS): 1. Patient's global assessment; 2. Patient's assessment of back pain; 3. Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) average of 10 questions; 4. Inflammation represented by mean duration and severity of morning stiffness, on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). 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. A higher score on the VAS signifies higher severity.

The Assessment of SpondyloArthritis International Society (ASAS) partial remission response criteria consisted of the following assessment domains measured on visual analogue scales (VAS): 1. Patient's global assessment; 2. Patient's assessment of back pain; 3. Function represented by BASFI average of 10 questions regarding ability to perform specific tasks; 4. Inflammation represented by mean duration and severity of morning stiffness, on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). The ASAS partial remission criteria was defined as a value not above 2 units in each of the four domains on a scale of 10.

The Ankylosing Spondylitis Disease Activity Score (ASDAS) is a composite index to assess disease activity in AS. Parameters used for the ASDAS include spinal pain (BASDAI question 2), the patient's global assessment of disease activity, peripheral pain/swelling (BASDAI question 3), duration of morning stiffness (BASDAI question 6) and C-reactive protein (CRP) in mg/L (Sieper 2009, Lukas 2009). Disease activity states are inactive disease, moderate disease activity, high disease activity, and very high disease activity. The 3 values selected to separate these states were < 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 were a change ≥ 1.1 unit for "minimal clinically important improvement" and a change ≥ 2.0 units for "major improvement" (Machado 2011).