Fri0388 secukinumab Improves Health-Related Quality of Life in Patients With Ankylosing Spondylitis, Irrespective of Time Since First Diagnosis: Pooled Results From the Secukinumab Phase 3 Trial Program

Abstract

BackgroundAnkylosing spondylitis (AS) is a chronic rheumatic condition that has a negative impact on health-related quality of life (HRQoL). Secukinumab (SEC), a fully human anti-IL-17A monoclonal antibody, has been shown to effectively control AS symptoms and improve HRQoL.ObjectivesTo evaluate the impact of SEC on HRQoL, assessed by the Short Form-36 Health Survey (SF-36), in pts with active AS stratified by time since first diagnosis (<2 or ≥2 yrs).MethodsPts were randomized to placebo (PBO) or SEC in MEASURE 1 (10 mg/kg intravenously followed by 150 or 75 mg SC), MEASURE 2 (150 or 75 mg SC) and MEASURE 4 (150 mg SC with/without SC loading). At Wk 16 or Wk 24, depending on ASAS 20 response, pts on PBO were re-randomized to SEC. Mixed-models for repeated measures were used to evaluate changes in SF-36 from baseline (BL) to Wk 16; observed data are presented at Wk 52. The proportion of pts reporting improvements meeting/exceeding the minimal clinically important differences (MCID) for SF-36 physical (PCS responders) and mental component summary (MCS responders), and individual SF-36 domains was also assessed. Missing data were recorded as non-response and Fisher’s exact test was used to compare the proportion of responders between groups at Wk 16. Only pooled data for pts receiving the licensed dose of SEC (150 mg) are shown.ResultsOverall 739 patients were included, with 427 and 312 in the SEC 150 mg and PBO groups, respectively. Of those, 37% and 36% of the SEC and PBO groups, respectively, were classified as <2 yrs since first AS diagnosis (Overall: 37%). The mean time since AS diagnosis was similar for the PBO and SEC treatment groups in both the <2 yrs (approx. 0.80 yrs) and the ≥2 yrs subgroups (approx.11 yrs). The least squares mean (LSM) changes in PCS from BL to Wk 16 were increased with SEC 150 mg compared with PBO, in both <2 yrs (PBO: 2.11; 150 mg: 6.44, p<0.0001) and ≥2 yrs since diagnosis (PBO: 3.03; 150 mg: 5.82, p<0.0001) groups. Significant increases were also reported in LSM changes in MCS scores from BL to Wk 16 with SEC 150 mg in patients <2 yrs since diagnosis (PBO: 2.10; 150 mg: 5.53, p<0.01), but not in the ≥2 yrs group. Analysis of individual SF-36 domain scores showed improvements with SEC vs PBO in the overall population and in both time since diagnosis subgroups, except Role-Emotional and Mental Health in the ≥2 yrs group (Figure). At Wk 16, the proportions of PCS responders were significantly higher with SEC 150 mg vs PBO, regardless of time since diagnosis (<2 yrs: PBO = 50.0%, SEC = 73.6%, p<0.01; ≥2 yrs: PBO = 45.0%, SEC = 69.8%, p<0.0001). MCS responses were not significantly different with SEC vs PBO in either subgroup. Overall, improvements in SF-36 scores and clinically meaningful MCID responses with SEC were more prominent in the <2 yrs since diagnosis compared with the ≥2 yrs group. Improvements in PCS, MCS, individual SF-36 domains and overall MCID responses were sustained to Wk 52 with SEC 150 mg.ConclusionTreatment with SEC 150 mg resulted in significant, clinically meaning...

Secukinumab in axial spondyloarthritis: a narrative review of clinical evidence

“…69 In addition, higher age and longer disease duration are associated with a higher disease burden in axSpA. 70 In a pooled analysis of data from MEASURE 1–4, younger patients with shorter disease duration demonstrated greater responses in ASAS20/40, BASDAI, hsCRP and VAS disease activity/back pain scores with secukinumab than older patients with longer disease duration, emphasizing the importance of prompt diagnosis and treatment in axSpA. 70…”

“…69 In addition, higher age and longer disease duration are associated with a higher disease burden in axSpA. 70 In a pooled analysis of data from MEASURE 1-4, younger patients with shorter disease duration demonstrated greater responses in ASAS20/40, BASDAI, hsCRP and VAS disease activity/back pain scores with secukinumab than older patients with longer disease duration, emphasizing the importance of prompt diagnosis and treatment in axSpA. 70 As mentioned previously, elevated CRP levels are a predictor of treatment response in axSpA and are associated with pain and fatigue symptoms.…”

<p>Impact of Secukinumab on Patient-Reported Outcomes in the Treatment of Ankylosing Spondylitis: Current Perspectives</p>

“…This analysis showed a significantly higher proportion of patients receiving secukinumab 150 mg versus placebo had clinical meaningful improvements in SF-36 PCS at Week 16 (71.4% versus 46.6%, p < 0.0001). 45 The data also suggested an improvement in patients’ mental health, as a numerically greater proportion of the secukinumab 150 mg group versus the placebo group had clinically meaningful improvements in SF-36 MCS at Week 16 (53.7% versus 47.9%), but this difference did not reach statistical significance. 45 These improvements were consistent in patients who were anti-TNF-naïve and those who were anti-TNF-IR, although responses were more prominent in anti-TNF-naïve patients.…”

“…Changes in the SF-36 PCS and MCS were sustained across 52 weeks. 38,45 Lastly, the EQ-5D is another instrument for measuring general health status. It is categorized into five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression, which are crucial to the independence and function valued by patients with AS.…”

“…Improvements were more prominent in patients diagnosed more recently (< 2 years) compared with patients diagnosed longer ago (≥ 2 years). 58 Age has also been established as a predictor of treatment response in AS; on average, younger patients are more likely to display a robust response to treatment. [59][60][61] In an analysis including data pooled from MEASURE 1-4, treatment with secukinumab 150 mg or 300 mg led to rapid and sustained improvements in PROs such as SF-36 and VAS back pain scores at Week 16.…”