Achievement of Remission Endpoints with Secukinumab Over 3 Years in Active Ankylosing Spondylitis: Pooled Analysis of Two Phase 3 Studies

Abstract

Introduction: Clinical remission in patients with ankylosing spondylitis (AS) has been determined using composite indices such as the AS Disease Activity Score inactive disease (ASDAS-ID), Assessment of SpondyloArthritis international Society criteria partial remission (ASAS-PR), and low Bath AS Disease Activity Index (BASDAI) scores. The objective of this exploratory analysis was to evaluate the proportion of secukinumab-treated patients with AS achieving remission defined based on the ASDAS-ID (score < 1.3), ASAS-PR or BASDAI score ≤ 2.

Methods: The analysis pooled data from the MEASURE 1 and 2 studies over 3 years. The proportion of patients who achieved ASDAS-ID, ASAS-PR, or BASDAI ≤ 2 with secukinumab was compared with placebo at week 16; results for secukinumab-treated patients were summarized through week 156. Sustainability of each criterion was assessed from week 16 to 156 using shift analysis. The association between each of these criteria and specific patient-reported outcomes (PROs), such as health-related quality of life, function, fatigue, and work impairment, was also explored.

Results: At week 16, a higher proportion of secukinumab-treated patients versus placebo achieved ASDAS-ID (17.6 vs. 3.5%), ASAS-PR (15.4 vs. 4.1%), or BASDAI ≤ 2 (22.3 vs. 6.4%) criteria (all P < 0.0001), which were sustained through 156 weeks. Shift analysis showed that the majority of secukinumab-treated patients achieving remission at week 16 maintained their status at week 156 (ASDAS-ID, 57.1%; ASAS-PR, 68.0% and BASDAI ≤ 2, 74.3%). Remission was also associated with improved PROs over 156 weeks.

Conclusions: Secukinumab-treated patients maintained ASDAS-ID, ASAS-PR, or BASDAI ≤ 2 from week 16 up to 3 years. Patients who achieved at least one of the three responses/states, reported improvement in PROs, which suggests an association of clinical remission/ID with PROs in patients with active AS.

Trial registration: ClinicalTrials.gov: NCT01358175, NCT01863732, and NCT01649375.

Keywords: Ankylosing spondylitis; Axial spondyloarthritis; Biologics; Interleukin-17; Low disease activity; Patient-reported outcomes; Remission; Secukinumab.

Figures

Fig. 1

Proportion of patients with ASDAS-ID, ASAS-PR and BASDAI ≤ 2 through week 156 (FAS). Analysis is based on observed data. aN = 159 after week 104, bN = 161 after week 104. *P < 0.0001,†P < 0.001, §P < 0.01, and ‡P < 0.05 versus placebo; P values are from Fisher’s exact test and are displayed up to week 16, prior to placebo re-randomization. N = number of patients included in the analysis, n = number of evaluable patients. ASAS-PR Assessment of SpondyloArthritis international Society criteria for partial remission, ASDAS-ID Ankylosing Spondylitis Disease Activity Score for inactive disease, BASDAI Bath Ankylosing Spondylitis Disease Activity Index, FAS full analysis set

Fig. 2

Proportion of patients with ASDAS-ID, ASAS-PR, and BASDAI ≤ 2 through week 156 (by TNFi status). Analysis based on observed data. aN = 114 after week 104, bN = 114 after week 104, cN = 45 after week 104, dN = 47 after week 104. *P < 0.0001, †P < 0.001, §P < 0.01, ‡P < 0.05 versus placebo; P values are from Fisher’s exact test and are displayed up to week 16, prior to placebo re-randomization. N = number of patients included in the analysis, n = number of evaluable patients. IR Inadequate response, PR partial remission, TNFi tumor necrosis factor inhibitor

Fig. 3

Shift analysis from week 16. Proportion of patients with ASDAS-ID, ASAS-PR, and BASDAI ≤ 2 responses at weeks 104 or 156. Shift analysis was performed on mutually exclusive categories in patients for whom data were available at both week 16 and weeks 104 or 156. N = total number of patients included in the analysis, n = number of evaluable patients who completed week 16. HDA High disease activity (2.1–3.5), ID inactive disease (< 1.3); LDA, low disease activity (1.3 to < 2.1), VHDA very high disease activity (> 3.5)

Fig. 4

Association of ASDAS-ID, ASAS-PR, and BASDAI ≤ 2 with PROs (change from baseline to 156 weeks; coefficient in MMRM). Data are from MMRM, with analysis visit and TNFi status (overall pooled sample only) as factors, and weight, baseline score, and remission status as continuous covariates. Remission status by analysis visit is included as an interaction term in the model. An unstructured covariance structure is used for this model. ASQoL Ankylosing spondylitis (AS) Quality of Life, BASFI Bath AS Functional Index, CI confidence interval, FACIT Functional Assessment of Chronic Illness Therapy, MCS mental component summary of SF-36, MMRM mixed-effects models for repeated measures, PCS physical component summary of SF-36, PROs patient-reported outcomes, SF-36 Short-Form 36 health survey, WPAI-GH Work Productivity and Activity Impairment–General Health