Rheumatology.net

Rheumatology Xagena

Xagena Mappa
Medical Meeting
Pneumobase.it
Mediexplorer.it

Ixekizumab in ankylosing spondylitis: positive results from two phase 3 studies, COAST-V and COAST-W


Findings from two phase 3 studies, COAST-V and COAST-W, in adults with ankylosing spondylitis ( AS ), also referred to as radiographic axial spondyloarthritis ( axSpA ), were presented at the American College of Rheumatology ( ACR )/ Association of Rheumatology Health Professionals ( ARHP ) Annual Meeting in Chicago.
The analyses are part of a clinical development program that aims to evaluate Ixekizumab ( Taltz ) across various populations of patients with ankylosing spondylitis.

In both studies, Ixekizumab has demonstrated a statistically significant and clinically meaningful improvement in proportion of patients who achieved Assessment of Spondyloarthritis International Society 40 ( ASAS40 ) over 16 weeks compared to placebo.

ASAS40 represents at least a 40% improvement in disease signs and symptoms such as pain, inflammation and function.

COAST-V is the first successful trial in ankylosing spondylitis to use ASAS40, a stringent clinical measure indicating a high degree of clinical improvement as the primary endpoint, compared to the standard endpoint of ASAS20.

COAST-W is the first AS study to specifically focus on the difficult-to-treat population of patients who had an inadequate response to one or two tumor necrosis factor ( TNF ) inhibitors ( 90% of enrolled patients ) or intolerance to a TNF inhibitor ( 10% ).

COAST-V trial

COAST-V, which included 341 patients, is the first phase 3 study of Ixekizumab among patients with ankylosing spondylitis who had never received a biologic disease-modifying anti-rheumatic drug ( bDMARD ). It also is the first study to include both a placebo control arm and active reference arm ( Adalimumab ).

During the study, patients were treated with 80 mg of Ixekizumab subcutaneously either every four weeks or every two weeks ( following 80 mg or 160 mg starting dose at week 0 ), Adalimumab, or placebo.

At 16 weeks, 48% of patients treated with Ixekizumab every four weeks, 52% of patients treated with Ixekizumab every two weeks and 18% of patients treated with placebo achieved ASAS40, the primary endpoint of the study.

Ixekizumab has also demonstrated a statistically significant improvement on the following secondary endpoints, achieving the following response rates at 16 weeks:

ASAS20: 64% of patients treated with Ixekizumab every four weeks, 69% of patients treated with Ixekizumab every two weeks and 40% of patients treated with placebo achieved ASAS20;

BASDAI50: 42% of patients treated with Ixekizumab every four weeks, 43% of patients treated with Ixekizumab every two weeks and 17% of patients treated with placebo achieved a Bath Ankylosing Spondylitis Disease Activity Index 50 ( BASDAI50 );

MRI Spine SPARCC CFB: patients treated with Ixekizumab every four weeks experienced a -11.0 change from baseline ( CFB ) in MRI spine SpA Research Consortium of Canada ( SPARCC ) score, patients treated with Ixekizumab every two weeks experienced a -9.6 SPARCC CFB and patients treated with placebo experienced a -1.5 SPARCC CFB.

Ixekizumab has demonstrated significant improvements in disease activity, functional disability, and spinal and sacroiliac joint inflammation among patients with ankylosing spondylitis.

COAST-W trial

COAST-W is a phase 3 study of 316 patients with ankylosing spondylitis who had an inadequate response or were intolerant to one or two tumor necrosis factor ( TNF ) inhibitors.
COAST-W is the first dedicated study to measure the effect of biologic therapy in this patient population including spinal inflammation in patients with ankylosing spondylitis by using magnetic resonance imaging ( MRI ).

During the study, patients were treated with 80 mg of Ixekizumab subcutaneously either every four weeks or every two weeks ( following 80 mg or 160 mg starting dose at week 0 ), or placebo.

At 16 weeks, 25% of patients treated with Ixekizumab every four weeks, 31% of patients treated with Ixekizumab every two weeks and 13% of patients treated with placebo achieved ASAS40, the primary endpoint of the study.

In addition, patients treated with Ixekizumab achieved the following response rates at 16 weeks:

ASAS20: 48% of patients treated with Ixekizumab every four weeks, 47% of patients treated with Ixekizumab every two weeks and 30% of patients treated with placebo achieved ASAS20;

BASDAI CFB: patients treated with Ixekizumab every four weeks and patients treated with Ixekizumab every two weeks experienced a statistically significant reduction in disease activity compared to placebo as measured by BASDAI ( -2.2±0.2 , -2.1±0.2 and -0.9±0.2 respectively );

MRI SPARCC Spine CFB: patients treated with Ixekizumab every four weeks and patients treated with Ixekizumab every two weeks experienced a statistically significant reduction in spinal MRI inflammation compared to placebo as measured by the CFB in MRI spine SPARCC score ( -3.0, -4.0 and 3.3, respectively ).


In both COAST-V and COAST-W, the 80 mg Q2W and Q4W dosing regimens have demonstrated similar safety profiles.
There were no new or unexpected safety findings in the AS population, compared to the psoriasis and psoriatic arthritis populations.

Ixekizumab is a monoclonal antibody that selectively binds with interleukin 17A ( IL-17A ) cytokine and inhibits its interaction with the IL-17 receptor.
IL-17A is a naturally occurring cytokine that is involved in normal inflammatory and immune responses.
Ixekizumab inhibits the release of pro-inflammatory cytokines and chemokines. ( Xagena )

Source: Lilly, 2018

XagenaMedicine_2018



Indietro