Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that ravages the axial skeleton and sacroiliac joints. It involves two subtypes: radiographic axSpA (r-axSpA) and nonradiographic axSpA (nr-axSpA). As their names imply, these subtypes differ based on the presence or absence of frank radiographic sacroiliitis on X-ray.

The goal of treatment for axSpA is to maximize long-term health-related quality of life via the control of inflammatory symptoms, the prevention of progressive structural damage, and the preservation or normalization of social function. 

 

Insight into longer-term use of ixekizumab 

 

Publishing in Journal of Rheumatology, investigators reported on the safety and efficacy of ixekizumab from the COAST program through a study duration of 3 years.

Deodhar A, Poddubnyy D, Rahman P, et al. Long-term safety and efficacy of ixekizumab in patients with axial spondyloarthritis: 3-year data from the COAST program. J Rheumatol. 2023 May;50(5):718. Erratum for: J Rheumatol. 2023 Feb 15; PMID: 37127315.

 

 

Ixekizumab is a high-affinity monoclonal antibody that targets interleukin (IL)-17A. In the COAST program, it previously demonstrated efficacy at week 16, which held at 2 years in patients with r-axSpA and nr-axSpA. In addition, no new safety signals emerged.

 

Ixekizumab’s 3-year safety profile in the COAST program aligned with the previously established results. Sustained improvement of disease activity and clinically important improvement (CII) with use of ixekizumab q4 weeks was maintained in patients through 3 years. 

 

Determining the safety profile of a biologic from multiple studies and long-term extension studies is of the utmost importance for patients receiving longstanding treatment.

 

 

Exploring re-treatment with etanercept

 

The RE-EMBARK study assessed etanercept withdrawal and re-treatment in patients with nr-axSpA who had already achieved inactive disease.

Van den Bosch F, Wei JC, Nash P, et al. Etanercept withdrawal and retreatment in nonradiographic axial spondyloarthritis: results of RE-EMBARK, an open-label phase IV trial. J Rheumatol. 2023 Apr;50(4):478–487.

 

Requested by the European Medicines Agency (EMA), RE-EMBARK is a postapproval study examining the frequency of flares following etanercept withdrawal in patients with inactive disease, as well as the efficacy and safety of re-treatment following such flares. The post-hoc analysis examined predictors of the maintenance of inactive disease after ETN withdrawal, as well as predictors of re-achieving inactive disease after flare-ups and etanercept re-treatment.

 

“An early, aggressive, treat-to-target approach is recommended in axSpA to improve outcomes. Another benefit of this strategy may determine whether some patients can maintain remission after expensive biologic treatment is discontinued,” wrote the study authors.

“Results from RE-EMBARK suggest that treatment goals can be achieved even after ETN [etanercept] discontinuation in some (ie, 25%) patients. Studies of other TNFi medications—infliximab (IFX), adalimumab (ADA), certolizumab pegol (CZP), and ixekizumab—demonstrated sustained responses in a portion of patients with axSpA following treatment withdrawal. Moreover, many patients in remission and who flared following withdrawal regained inactive disease status after retreatment,” the authors added.

 

 

Leveraging bimekizumab across the axSpA spectrum

 

New treatments are an unmet need in axSpA, as it is a complex disease with widely heterogeneous clinical presentations. BE MOBILE 1 and BE MOBILE 2—which involve nr-axSpA and r-axSpA patients, respectively—are double-blind phase 3 trials that examine the efficacy and safety of bimekizumab. This monoclonal antibody is a novel dual IL-17A/IL-17F inhibitor and can be used for a gamut of axSpA symptomatic presentations.

van der Heijde D, Deodhar A, Baraliakos X, et al. Efficacy and safety of bimekizumab in axial spondyloarthritis: results of two parallel phase 3 randomised controlled trials. Ann Rheum Dis. 2023 Jan 17;82(4):515–526. Erratum in: Ann Rheum Dis. 2023 Sep;82(9):e213.

 

 

Compared with the placebo arm, dual inhibition of IL-17A and IL-17F with bimekizumab yielded swift improvements in efficacy outcomes, as well as being well tolerated in nr-axSpA and r-axSpA patients.

Improvements were observed in the Ankylosing Spondylitis Disease Activity Score (ASDAS) states, and objective measures of inflammation such as hs-CRP and MRI of the sacroiliac joints and spines were also ameliorated.

 

“The positive findings from the BE MOBILE 1 study provide clear evidence supporting bimekizumab in the treatment of nr-axSpA, and suggest that targeting IL-17F in addition to IL-17A may be a promising treatment approach for this painful, chronic rheumatic condition that often starts in young adulthood,” said rheumatologist Atul Deodhar, MD, one of the study investigators, to the Spondylitis Association of America (SAA).

A new biologic medication, bimekizumab, shows promise for axial spondyloarthritis. Spondylitis Association of America. January 26, 2022.