Secukinumab Provides Sustained Improvements in AS

June 10, 2016

EULAR 2016: Secukinumab prevents radiographic progression in 80 percent of ankylosing spondylitis patients and provides sustained improvements.

New studies presented this week show that secukinumab is effective in preventing radiographic progression in 80 percent of ankylosing spondylitis (AS) patients and provides sustained improvements.

The studies were presented this week at the annual meeting of the European League Against Rheumatism Annual Congress (EULAR 2016) in London.

The first study1, a phase II study called MEASURE I, included 1,371 patients with ankylosing spondylitis who were randomized to secukinumab or placebo groups. Patients on secukinumab received a 10 mg/kg intravenous loading dose at baseline and then again at weeks two and four. And, then, 150 or 75 mg subcutaneously every four weeks from week eight. The placebo patients were re-randomized to secukinumab 150 or 75 mg subcutaneously (q4w) based on the ASAS response criteria (ASAS 20) at week 16 (non-responders switched at week 16; responders at week 24).

Researchers found no major radiographic differences for either 150 mg and 75 mg dose groups.  At baseline, 62 percent of 168 patients had syndesmophytes; 63 percent had elevated (>5 mg/L) CRP levels; 25 percent were smokers; and, 73 percent were male.  [[{"type":"media","view_mode":"media_crop","fid":"49445","attributes":{"alt":"©SutthaBurawonk/Shutterstock.com","class":"media-image media-image-right","id":"media_crop_4529691248045","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"5972","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"font-size: 13.008px; line-height: 1.538em; float: right;","title":"©SutthaBurawonk/Shutterstock.com","typeof":"foaf:Image"}}]]

The mean change from baseline and week 104 was 0.30±2.53. Approximately 80 percent of patients showed no radiographic progression from baseline to week 104. At week 104, new syndesmophytes were found in 5 percent of patients who were without syndesmophytes at baseline. Changes were higher in male patients and patients who had syndesmophytes or elevated CRP at baseline.

Approximately 70 percent of patients with syndesmophytes at baseline developed no additional syndesmophytes through week 104. Overall, baseline Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and mean mSASSS change at week 104 were higher in males (mean change 0.38±2.79 vs 0.08±1.58 in females), in patients with baseline syndesmophytes (0.47±3.20 vs 0.02±0.26 in pts with no BL syndesmophytes), or patients with elevated CRP levels at baseline (0.47±2.66 vs 0.02±2.27 in pts with normal CRP levels).

Sustained Improvement

In the second study2 , researchers found that secukinumab provided sustained improvement over two years in the signs and symptoms of ankylosing spondylitis with improved physical function, regardless of anti-TNF status.

The study is based on data from the 104-week secukinumab MEASURE 2 study. It included 219 patients with active ankylosing spondylitis. The patients were randomized to subcutaneous secukinumab 150 or 75 mg or PBO at baseline, weeks one, two and three and every four weeks from week four.

At week 16, 16, PBO-treated subjects were assigned to secukinumab 150 or 75 mg s.c. q4w. At baseline, 39 percent of subjects had an inadequate response/intolerance to prior anti-TNF therapy (anti–TNF-IR). Primary endpoint was ASAS20 response rates at week 16. Secondary endpoints included ASAS40, hsCRP, ASAS5/6, BASDAI, SF-36 PCS and ASAS partial remission.

Eighty three percent of 72 patients, 78 percent of 73 patients and 77 percent of 74 patients completed 104 weeks of treatment with secukinumab 150 mg, 75 mg and PBO, respectively.

With 150 mg secukinumab, significant improvements were seen in all endpoints at week 16 (except ASAS partial remission). The 75 mg dose did not reach statistical significance at week 16.

ASAS20/40 response rates at week 104 were 71.5/47.5 percent with both secukinumab doses.

Clinical improvements with secukinumab were sustained through week 104 across all secondary endpoints. In the subgroup of anti–TNF-naive subjects, ASAS20/40 response rates at week 104 (observed data) were 76.9/56.4 percent and 80.0/60.0 percent with secukinumab 150 mg and 75 mg, respectively. Corresponding rates in anti–TNF-IR subjects were 85.0/50.0 percent and 68.8/43.8 percent.

 

Disclosures:

The authors of each of the studies disclose a number of potential conflicts of interest. The first study cited here was sponsored by Novartis Pharma AG.

References:

1.       J. Braun,  X. Baraliakos, et al.  “Effect of Secukinumab, an Interleukin-17a Inhibitor, On Spinal Radiographic Changes Through 2 Years in Patients With Active Ankylosing Spondylitis: Results of The Phase 3 Study, Measure 1.” EULAR 2016. Abstract number:  OP0001

2.       H. Marzo-Ortega, C. W. Legerton, et al. “Secukinumab Provides Sustained Improvements in The Signs And Symptoms of Active Ankylosing Spondylitis: 2-Year Results From A Phase 3 Trial With Subcutaneous Loading and Maintenance Dosing (Measure 2). Abstract number:  SAT0396  EULAR 2016. https://b-com.mci-group.com/Abstract/Statistics/AbstractStatisticsViewPage.aspx?AbstractID=300993

3.       P. Emery, D. Baeten, et al. “Secukinumab Improves Physical Function And Quality of Life In Patients With Active Ankylosing Spondylitis: 2-Year Data From Measure 1, A Phase 3 Randomised Trial.” Abstract number:  Sat0410. EULAR 2016.  https://b-com.mci-group.com/Abstract/Statistics/AbstractStatisticsViewPage.aspx?AbstractID=300995