Effect of Secukinumab on Patient-Reported Outcomes in Active Ankylosing Spondylitis

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Effect of Secukinumab on Patient-Reported Outcomes in Active Ankylosing Spondylitis

Ankylosing spondylitis (AS) is a chronic immune-mediated inflammatory disease with worldwide prevalence of about 0.2–1.4%. The advancement of AS may result in structural damage of the spine, worsening of joint function, physical disability, and significant functional impairment, culminating in reduced health related quality of life (HRQoL).

Key conclusion: 

Secukinumab offers considerable and sustained improvements in patient-reported disease activity and health-related quality of life (HRQoL) by reducing functional impairment, fatigue, and impact on work productivity in patients with active ankylosing spondylitis (AS).

ABSTRACT: 
Background: 

Ankylosing spondylitis (AS) is a chronic immune-mediated inflammatory disease with worldwide prevalence of about 0.2–1.4%. The advancement of AS may result in structural damage of the spine, worsening of joint function, physical disability, and significant functional impairment, culminating in reduced health related quality of life (HRQoL). Patients with AS also experience reduced social functioning and work disability. Conventional intervention options for patients with AS are nonsteroidal anti-inflammatory drugs (NSAIDs) and physical therapy. However, the long-term use of NSAID is linked to gastrointestinal and cardiovascular adverse events, while disease-modifying antirheumatic drugs have limited efficacy. Therefore, anti–tumor necrosis factor (anti-TNF) therapy is suggested in those who fail to attain satisfactory disease control with NSAIDs or those patients with high disease activity.

Anti-TNF therapies have shown to improve outcomes in patients with AS. However, patients with moderate or severe disease (25%-40%) do not respond to or are intolerant of anti-TNF agents. Thus, there is a need for new therapies providing long-term disease control in AS patients. Therapeutic strategies targeting various inflammatory pathways, including interleukin-6 receptor (IL-6R) blockade, T cell costimulation inhibition, and IL-1R antagonism, have largely failed to show significant clinical efficacy in AS. Elevated levels of IL-17–producing cells are found in the circulation and target tissues of patients with this AS, suggesting that IL-17A contributes to the pathogenesis of AS.

Secukinumab is a high-affinity, fully human IgG1k monoclonal antibody that selectively binds to and neutralizes IL-17A. In a phase II proof-of concept trial, secukinumab was well tolerated and rapidly reduced clinical and biologic signs of active AS.

Rationale behind research

  • MEASURE 1 study is an ongoing, 2-year, phase III, randomized trial, followed by a 3-year extension period, designed to assess the long-term efficacy and safety of secukinumab in patients with active AS. Secukinumab was shown to improve the signs and symptoms of AS through the first 52 weeks of therapy.
  • The present study was conduted to report the effects of secukinumab treatment over 52 weeks on patient-reported outcomes.

Objective

To evaluate the effect of secukinumab (IL-17A inhibitor) on patient-reported outcomes in patients with active ankylosing spondylitis.

Methods: 

 

  • Study outcomes
  • Patient Reported Outcomes: The patient-reported outcomes were assessed as prespecified end points and included mean change in BASDAI, Short Form 36 (SF-36) health survey physical component summary (PCS) score, SF-36 mental component summary (MCS) score, Ankylosing Spondylitis Quality of Life (ASQoL) measure, Bath Ankylosing Spondylitis Functional Index (BASFI), EuroQol 5-domain (EQ-5D) questionnaire, Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F), and Work Productivity and Activity Impairment–General Health (WPAI-GH). Additional assessments included the proportion of patients in whom BASDAI 50 was achieved (defined as at least a 50% improvement [decrease] from baseline in the total BASDAI score) and the proportion of patients with improvements from baseline in the SF-36 PCS and MCS that exceeded the minimum clinically important difference (MCID; defined as an improvement of  ≥2.5 points) at week 16 and other time points.

Time Points: Baseline, week 16 and 52

Results: 

 

Outcomes

Baseline characteristics: Baseline demographics, disease characteristics, and prior or concomitant medication use were similar across all the study groups.

Patient reported outcomes:

At week 16, secukinumab IV=150 mg or IV=75 mg was associated with statistically and clinically significant improvements from baseline versus placebo in the BASDAI (22.3 for both regimens versus 20.6; P<0.0001 and P<0.001, respectively), SF-36 PCS (5.6 for both regimens versus 1.0; P<0.0001 and P<0.001, respectively), and ASQoL (23.6 for both regimens versus 21.0; P< 0.0001 and P<0.001, respectively).

Figure 1: Change in BASDAI from baseline to week 16 and week 52 with secukinumab 150 mg

Figure 2: Change in BASDAI from baseline to week 16 and week 52 with secukinumab 75 mg

Figure 3: Change in BASDAI from baseline to week 16 and week 52 with secukinumab 75 mg

  • Clinically significant improvements in the SF-36 MCS, BASFI, EQ-5D, and BASDAI 50 were observed with both secukinumab groups versus placebo at week 16; improvements were also observed in the FACIT-F and WPAIGH. All improvements were sustained through week 52.
Conclusion: 

The 52-week results from the MEASURE 1 study demonstrated significant and sustained improvements in the signs and symptoms of AS with secukinumab. Additionally, the patient-reported outcomes assessed showed that patients treated with secukinumab showed statistically and clinically significant improvements in multiple facets of physical functioning and HRQoL at week 16 compared with those treated with placebo. The improvements were sustained in the secukinumab regimens over the long-term, i.e., through week 52.

These results are clinically meaningful, since patients with active AS experience poor HRQoL due to back pain, discomfort, and fatigue, which ultimately restricts their physical function and work productivity. The significant improvements observed with both secukinumab regimens versus placebo at week 16 in BASDAI, SF-36 PCS, and ASQoL were maintained irrespective of the baseline anti-TNF status of the patients. Improvements in BASDAI scores were also better with secukinumab versus placebo at week 16 regardless of baseline hsCRP level and were sustained up to week 52. All improvements observed at week 16 were sustained through week 52, and the OR favored better responses with the 2 secukinumab regimens versus placebo. Both secukinumab regimens provided improvements in BASFI scores and all 5 domains of health status on the EQ-5D in comparison to placebo, suggesting improvements in the physical function and health status of the patients receiving secukinumab.

Arthritis & Rheumatology 2016;68(12):2901–2910

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