Ixekizumab (Taltz®) shows promise in treating non-radiographic axial spondyloarthritis

December 2019

The IL-17 inhibitor biologic, Ixekizumab (Taltz®) was found effective in reducing signs, symptoms, and inflammation in those with non-radiographic axial spondyloarthritis (nr-axSpA) in a recent phase 3 clinical trial study.

“[Ixekizumab] improved the signs and symptoms of non-radiographic axSpA as measured by ASAS40^[1], as well as reduced inflammation on MRI, an important objective measure of disease activity,” said Atul Deodhar, M.D., professor of medicine at Oregon Health & Science University, SAA’s Medical Board Member, and principal investigator of the study, officially titled, “A 52-week multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of Ixekizumab (LY2439821) in bDMARD naive patients with non-radiographic axial spondyloarthritis.”

Criteria for participation in the study included: Adults with a diagnosis of axial spondyloarthritis according to the Assessment of Spondyloarthritis International Society Classification (but not the modified New York criteria for ankylosing spondylitis – that is to say, not showing sacroiliac joint fusion on x-ray), who:

• • Have inadequate response to nonsteroidal anti-inflammatory drugs (NSAIDs),
  • Have BASDAI ^[2] scores of over 4, and back pain scores of over 4,
  • Show signs of active inflammation such as MRI evidence of sacroiliac joint inflammation, or systemic inflammation seen in the blood, as measured by CRP levels ^[3] of >5 mg/L].

A total of 303 study participants were placed in three groups: the Q4W group (treated with 80mg of Ixekizumab every 4 weeks), Q2W group (treated with 80mg of Ixekizumab every 2 weeks), and the placebo group that received an inactive substance (sugar pill).

The following chart demonstrates the percentage of participants showing meaningful improvement in the signs and symptoms of nr-axSpA at week 16, and week 52 of the study, as measured by the Assessment of Spondyloarthritis International Society Response) criteria (ASAS40¹).

Overall the results were promising, as over a third of those taking the study medication every two weeks, as well as of those taking it every four weeks, reported meaningful improvements (reaching ASAS 40 criteria of 40% or greater improvement in signs and symptoms) at week 16 and week 52 of the study. Furthermore, Ixekizumab showed stronger results when combined with conventional background medications (NSAIDs, DMARDs, pain medications, and low dose corticosteroids) for the improvement of inflammation, and other signs and symptoms.

Ixekizumab was approved for ankylosing spondylitis in August of 2019.

Currently there is only one biologic medication FDA approved for use in non-radiographic axial spondyloarthritis, the TNF inhibitor Certolizumab pegol (CIMZIA^®). This study’s results are promising for patients and physicians looking for additional treatment options.

***Dr. Atul Deodhar and Dr. Lianne Gensler, members of SAA’s Medical and Scientific Advisory Board, were among the authors of this study.

[1] The ASAS Response Criteria (ASAS 40) is defined as an improvement of at least 40% and an absolute improvement of at least 10 units on a 0-100 scale in at least three of the following domains: Patient global assessment, Pain assessment, Function (BASFI), and Inflammation (last 2 questions of BASDAI).

[2] The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) is an established self-administered measurement tool which allows a physician to determine the effectiveness of a current drug therapy by measuring severity of fatigue, spinal and peripheral joint pain, localized tenderness, and morning stiffness. Scores range from 0 (best) to 10 (worst); a score >4 indicates active disease.

[3] C-reactive protein (CRP) is a blood marker for inflammation in the body. CRP is produced in the liver and its level is measured by testing the blood. CRP is classified as an acute phase reactant, which means that its levels will rise in response to inflammation.

References:

Deodhar A, van der Heijde D, Gensler L, Kim T, Maksymowych W, Østergaard M, Poddubnyy D, Marzo-Ortega H, Bessette L, Tomita T, Gallo G, Adams D, Leung A, Zhao F, Hojnik M, Carlier H, Sieper J. Ixekizumab in Non-Radiographic Axial Spondyloarthritis: Primary Results from a Phase 3 Trial [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/ixekizumab-in-non-radiographic-axial-spondyloarthritis-primary-results-from-a-phase-3-trial/.  Accessed December 4, 2019.

Rao, Meghna. “Ixekizumab Superior to Placebo in Improving Symptoms, Inflammation in Non-radiographic Axial Spondyloarthritis.” Rheumatology Advisor, 18 Nov. 2019, www.rheumatologyadvisor.com/home/conference-highlights/in-depth-focus-from-acr-2019-spa/ixekizumab-superior-to-placebo-in-improving-symptoms-inflammation-in-nonradiographic-axial-spondyloarthritis/.