IL-17A Inhibitor Secukinumab New Treatment Ankylosing Spondylitis

The IL-17A Inhibitor Secukinumab as a New Treatment for Ankylosing Spondylitis

IL-17A inhibitor Secukinumab – ankylosing spondylitis

Update at BrainImmuneAccording to the Arthritis Foundation (Atlanta, GA), studies presented at this year’s American College of Rheumatology annual meeting in Boston (November 14–19) indicate that treatment with secukinumab may turn out to be a promising new therapeutic approach in ankylosing spondylitis (AS).

Secukinumab (a fully human antibody to IL-17A), selectively binds to and neutralizes interleukin (IL)-17A, thus, inhibiting the release of other pro-inflammatory mediators and cytokines. Interleukin-17 is an immune ‘hormone’ or cytokine involved in several autoimmune/inflammatory conditions, and a therapeutic target in several common human diseases. In 2013, Baeten D. et al. reported that secukinumab rapidly reduced clinical signs of active ankylosing spondylitis, and was the first targeted therapy that is an alternative to TNF inhibition (Lancet, 2013, 382:1705-13).

According to two recent Novartis media releases, secukinumab meets primary endpoint in Phase III studies showing improvement in active ankylosing spondylitis patients’ symptoms versus placebo; “more than 60% of secukinumab 150 mg patients achieved significant improvements in AS symptoms, seen as early as Week 1 and sustained through one year of treatment”. Of note, up to 40% of patients have an inadequate or no response to standard anti-TNF medicines, currently the only biologic therapies available for ankylosing spondylitis.

Updates

A 2015 study by Dominique Baeten et al., published in the New England Journal of Medicine (NEJM) conducted two phase 3 trials of secukinumab in patients with active ankylosing spondylitis. Secukinumab significantly reduced the signs and symptoms of ankylosing spondylitis, as compared with placebo, in both phase 3 trials.

The investigators concluded that Secukinumab at a subcutaneous dose of 150 mg, with either subcutaneous or intravenous loading, provided significant reductions in the signs and symptoms of ankylosing spondylitis at week 16. Secukinumab at a subcutaneous dose of 75 mg resulted in significant improvement only with a higher intravenous loading dose. Collectively the studies form the largest clinical trial program ever conducted in AS, involving 590 patients.

On January 15, 2016, Novartis announced that the US Food and Drug Administration (FDA) has approved Cosentyx® (secukinumab) for the treatment of two new indications – adults with active ankylosing spondylitis (AS) and active psoriatic arthritis (PsA). The two new indications follow the earlier FDA approval for Cosentyx in January 2015 to treat adult patients with moderate-to-severe plaque psoriasis, and European approval for AS and PsA in November 2015.

A 2019 study by Jürgen Braun et al., published in Rheumatology (Oxford), evaluated the effect of secukinumab on efficacy, imaging outcomes, and safety through 4 years in patients with ankylosing spondylitis.

The investigators demonstrate the sustained efficacy of secukinumab in both clinical and radiographic outcomes through 4 years in the MEASURE 1 study, the first study reporting the longer-term effect of secukinumab on radiographic structural progression in AS.

The authors report that clinical improvements were sustained across all endpoints through Wk208, with numerically greater improvements with secukinumab 150 vs 75 mg. These results represent the longest-term efficacy results reported for this type of drug in AS, and are notable for demonstrating no evidence of decreasing efficacy with long-term use in both observed and imputed analyses, in contrast to the secondary treatment failure reported with long-term use of anti-TNF agents.

According to a 2019 review by Hannah A. Blair, published in Drugs the updated ASAS-European League Against Rheumatism (EULAR) guidelines recommend that biologic disease-modifying antirheumatic drugs should be considered in patients with persistently high disease activity despite conventional treatments (including NSAIDs). The UK National Institute for Health and Care Excellence (NICE) recommends secukinumab as an option for treating active AS in adults whose disease has responded inadequately to conventional NSAID or TNF inhibitor therapy.

The author concludes that secukinumab is effective and generally well tolerated for the treatment of adults with active AS, with efficacy and tolerability sustained over the longer term. Secukinumab is an effective therapy for TNF inhibitor-naive patients with active AS, and provides a useful treatment option for patients who have an inadequate response to or are intolerant of TNF inhibitors.

A 2020 study by Maria Chimenti et al., published in Expert Opinion on Biological Therapy confirms the effectiveness of the secukinumab in the treatment of with ankylosing spondylitis and psoriatic arthritis in a real-life multicenter setting. The drug was effective in reducing the severity and frequency of enthesitis, and a reduction in the concomitant use of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and glucocorticoids was seen during follow-up. Thus, clinicians might consider the use of secukinumab in patients who are unsuitable for csDMARDs or glucocorticoids, at least in monotherapy.

A 2021 study by Jürgen Braun et al., published in Arthritis Research & Therapy, investigated the efficacy of secukinumab in patients with active non-radiographic axial spondyloarthritis (nr-axSpA) grouped by disease activity as assessed by C-reactive protein (CRP) levels and/or magnetic resonance imaging (MRI) scores, human leukocyte antigen (HLA)-B27 status, and sex.

The authors of this study concluded that secukinumab improved the signs and symptoms of nr-axSpA across patient subgroups based on CRP (+/−) and/or MRI (+/−) status, HLA-B27 (+/−) status, and sex. The highest treatment differences between secukinumab and placebo were observed in patients with both elevated CRP levels and evidence of sacroiliitis on MRI, and in male patients, whereas the difference was minimal between HLA-B27 positive and negative subgroups.

A 2023 study by Francesco Molica Colella et al., published in Advances in Rheumatology reports a high effectiveness and tolerability profile for secukinumab in the real-life management of patients with ankylosing spondylitis and psoriatic arthritis. Secukinumab is overall effective regardless of disease duration and previous experience with TNFi. Patients with the highest disease activity at baseline ultimately show the greatest score reductions.


Cover Image Credit (Left Panel): The five interleukin-17 receptor (IL-17R) complexes and their corresponding ligands. IL-17B binds to the receptor complex composed of the IL-17RB subunit and an unknown subunit. IL-17A and IL-17F are stimulated by T-helper-17 (TH17) cells and bind to the IL-17RC and IL-17RA receptor complex (not shown: IL-17A/IL-17F heterodimers also bind to this receptor complex). IL-17E (IL-25) binds to the IL-17RB and IL-17RA receptor complex. IL-17C binds to the IL-17RE and IL-17RA receptor complex. The ligand for the IL-17RD and IL-17RA receptor complex is currently unknown. Secukinumab inhibits IL-17A and prevents it from binding to its receptor. From: Secukinumab: a review of the anti-IL-17A biologic for the treatment of psoriasis, Jillian Frieder et al. Ther Adv Chronic Dis 2018 Jan;9(1):5-21.