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Highlights from

American College of Rheumatology

annual meeting 2018

Chicago, Illinois 19-24 October 2018

3-year data on secukinumab in ankylosing spondylitis support efficacy and safety profile

Take-home messages
  • Secukinumab at 150 mg and 300 mg doses provided sustained improvement in signs and symptoms from baseline
  • Higher hurdle endpoints, eg ASAS40, showed a better response at 300 mg versus 150 mg secukinumab
  • Improvement was regardless of anti-TNF-alpha therapy status
"Overall we see two things, that is a persistency from year 1 to 3, and an additional separation between the 150 and 300 mg groups with the high hurdle [ASAS 40].”

Dr Alan Kivitz Rheumatologist, Altoona Center for Clinical Research, Duncansville, US

Secukinumab at both 300 mg and 150 mg doses provided sustained improvements in signs and symptoms of active ankylosing spondylitis (AS) from baseline through to 3 years, show the end-of-study data from the MEASURE-3 study.

In particular, responses were numerically higher with secukinumab 300 mg compared with the lower dose for higher hurdle efficacy endpoints.

The results, presented at the 2018 American College of Rheumatology/ Association of Rheumatology Health Professionals (ACR/ARHP) Annual Meeting, are a longer-term follow-up of the MEASURE-3 phase III study in patients with active AS. Results that comprised the primary endpoint of 16-week Assessment of SpondyloArthritis International Society criteria for 20% improvement (ASAS20) were presented previously.

Dr Alan Kivitz, a rheumatologist from the Altoona Center for Clinical Research, Duncansville, US, presented the 3-year results. “Both the 150 mg and 300 mg doses of secukinumab provided sustained improvements in signs and symptoms of active AS through to 3 years, but responses were numerically higher with 300 mg than 150 mg secukinumab for higher hurdle endpoints. Improvement was seen regardless of prior anti-TNF, and [the] safety [profile] was favourable and consistent through 3 years.”

A total of 226 patients of at least 18 years of age, with moderate-to-severe AS were randomly assigned to treatment with intravenous secukinumab 10 mg/kg at baseline, week 2, and 4 (loading regimen), followed by subcutaneous secukinumab 300 mg (n=76) or secukinumab 150 mg (n=74) beginning at week 8, or matched placebo (n=76). At week 16, placebo-treated patients were re-randomised to subcutaneous secukinumab 300 mg or 150 mg.

Just under half of participants were men, and mean age was around 42 years, mean time since diagnosis of AS was 5-6 years. Around 77% were anti-TNF-alpha naive, and the total Bath ankylosing spondylitis disease activity index (BASDAI) score at baseline was 7 across all groups.

The double-blind, placebo-controlled, 3-year, phase III study had pre-specified endpoints including patients who were naive to anti-TNF-alpha therapy or showed anti-TNF-alpha inadequate response. Other week-156 efficacy endpoints included ASAS20/40 response rate, mean change from baseline in BASDAI, AS disease activity score (ASDAS) inactive disease (defined as ASDAS <1.3), ASAS partial remission response rate, and overall safety and tolerability profile.

ASAS20 response rate at week 16 in the secukinumab 300 mg and 150 mg groups versus placebo comprised the primary endpoint. In addition, secondary endpoints included improvements in ASAS40, ASAS 5/6, BASDAI, and ASAS partial remission responses, along with change in high-sensitivity C-reactive protein (hsCRP) levels from baseline.

“There was over 80% retention up to 3 years in both the 150 mg and the 300 mg of secukinumab arms,” reported Dr Kivitz. A total of 80.5% (n=91) of patients on any secukinumab at 300 mg, and 80.9% (n=89) patients on any secukinumab at 150 mg completed 156 weeks of treatment.

These long-term results include an analysis conducted at week 156 including patients initially randomised to secukinumab and those who switched from placebo to secukinumab at week 16 (any secukinumab 300 mg, n=113 and any secukinumab 150 mg, n=110).

ASAS20 was achieved by 75.3% by year 1 in the 300 mg arm and this was maintained through to year 3 (75.0%). In the 150 mg arm, 69.5% achieved ASAS20 at 1 year and this was maintained to 68.2% at 3 years. ASAS40 was achieved by 57.7% in year 1 and this was maintained to 56.5% by year 3 in the 300 mg group, while in the 150 mg group, 47.7% achieved ASAS40 at 1 year and this remained identical at 3 years.

“So, we are starting to see some more separation between the curves with the ASAS40. Overall, we see two things, that is a persistency from year 1 to 3, and an additional separation between the 150 and 300 mg groups with the high hurdle [ASAS40],” reported Dr Kivitz.

Secukinumab also maintained reduction in BASDAI over 3 years from -3.42 at 1 year and -3.56 at 3 years in the 300 mg patients, while those on 150 mg showed a reduction of -3.05 at 1 year and -2.75 at 3 years. Partial remission response rates were experienced by approximately 15% in the 150 mg group, persisting from 1 to 3 years; increasing from 25.8% at 1 year to 28.3% at 3 years in the 300 mg group.

The ASDAS-CRP inactive disease state was maintained through to 3 years for both 150 mg and 300 mg, at approximately 17% responders and 25% responders respectively.

Response was broken down by anti-TNF-alpha status (naive and inadequate response). Secukinumab sustained the ASAS20 across 3 years in both the 150 mg and 300 mg groups in the anti-TNF-alpha-naive group (approximately 73% and 77% respectively). In the anti-TNF-alpha inadequate response group, this increased from 52.4% to 64.7% at the 150 mg dose over 3 years, and from 65.0% to 76.5% at the 300 mg dose.

“We start to see the 300 mg outperform the 150 mg in the anti-TNF-alpha inadequate response group. With the ASAS40, the higher hurdle, we see lower numbers than ASAS20 and with the anti-TNF-alpha inadequate response group, we see increased separation between the two doses (over the 3 years 50.0% to 41.2% in the 300 mg, and 33.3% to 29.4% in the 150 mg).”

Regarding adverse events over 3 years, discontinuation due to adverse events was similar between doses (4.5% and 4.4% in the 150 mg and 300 mg respectively); serious infections were seen at 0.7% at both doses. “I would note that the rate is low at both doses and that no dose response effect was seen. There was also a low number of malignant tumours [1% and 0.3%; 150 mg and 300 mg, respectively]” reported Dr Kivitz.

Based on Kivitz A, Pavelka K et al. Sustained improvements in signs and symptoms of active ankylosing spondylitis and reassuring safety with secukinumab 300mg: 3-year results from a phase 3 study (abstract 1869). Presented on Monday 22 October 2018.

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The content and interpretation of these conference highlights are the views and comments of the speakers/authors.

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