Efficacy and safety of interleukin-17A inhibitors in patients with ankylosing spondylitis: a systematic review and meta-analysis of randomized controlled trials

Wang, Peng; Zhang, Shuo; Hu, Binwu; Liu, Weijian; Lv, Xiao; Chen, Songfeng; Shao, Zhimin

doi:10.1007/s10067-020-05545-y

Cited by 18 publications

(15 citation statements)

References 58 publications

(84 reference statements)

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“…A recent meta-analysis of IL-17A inhibitor trials in AS patients found that the risk of serious adverse events and serious infections did not differ significantly between active treatment and placebo (40). However, inhibition of IL-17 is known to increase susceptibility to mucosal infections by Candida species, which reflects the role of type 17 immunity at the oral mucosa (41)(42)(43)(44).…”

Section: Discussionmentioning

confidence: 99%

Safety and Efficacy of Bimekizumab in Patients With Active Ankylosing Spondylitis: Three‐Year Results From a Phase IIb Randomized Controlled Trial and Its Open‐Label Extension Study

Baraliakos

Deodhar

Dougados

et al. 2022

Arthritis & Rheumatology

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and Désirée van der Heijde 11Objective. To assess the long-term safety, tolerability, and efficacy of bimekizumab in patients with active ankylosing spondylitis (AS).Methods. Patients with active AS who completed the dose-ranging, 48-week BE AGILE randomized controlled trial were eligible to participate in an open-label extension (OLE) study, in which patients received 160 mg of bimekizumab every 4 weeks. We present the safety and efficacy results through 156 weeks. Missing efficacy data were imputed using nonresponder imputation analysis for binary outcomes and multiple imputation for continuous outcomes.Results. From weeks 0-156, 280 of 303 patients (exposure-adjusted incidence rate 141.0 per 100 patient-years) experienced ≥1 treatment-emergent adverse event; the most frequent adverse events were nasopharyngitis (8.1 per 100 patient-years) and upper respiratory tract infection (5.0 per 100 patient-years). Additionally, 67 of 303 patients (9.8 per 100 patient-years) had mild to moderate localized fungal infections (28 of 303 patients had Candida infections [3.7 per 100 patient-years] and 23 of 303 patients had oral candidiasis [3.0 per 100 patient-years]), 10 patients had serious infections (1.3 per 100 patient-years), and no cases of active tuberculosis were reported. Active inflammatory bowel disease (1.1 per 100 patient-years), anterior uveitis (0.7 per 100 patient-years), and adjudicated major adverse cardiovascular events (0.3 per 100 patient-years) were infrequent. The efficacy of bimekizumab treatment demonstrated at week 48 was sustained in the OLE study. At week 156, nonresponder imputation analysis showed that 53.7% of patients (72.6% of observed cases) met the Assessment of SpondyloArthritis international Society criteria for 40% improvement and 28.0% of patients (37.9% of observed cases) achieved partial remission; Ankylosing Spondylitis Disease Activity Scores were reduced from baseline (mean ± SEM 3.9 ± 0.1) to week 48 (2.1 ± 0.1) and week 156 (1.9 ± 0.1) (multiple imputation). Patients showed sustained improvements in pain, fatigue, physical function, and health-related quality of life.Conclusion. The safety profile of bimekizumab was found to be consistent with previously demonstrated findings, and no new safety signals were identified. The efficacy of bimekizumab in patients with AS was sustained through 3 years of treatment.

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Section: Discussionmentioning

confidence: 99%

Safety and Efficacy of Bimekizumab in Patients With Active Ankylosing Spondylitis: Three‐Year Results From a Phase IIb Randomized Controlled Trial and Its Open‐Label Extension Study

Baraliakos

Deodhar

Dougados

et al. 2022

Arthritis & Rheumatology

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“…Patients with PsA with axial manifestations seem to have a good response to the same biologics as patients with axSpA, a fact recently confirmed with IL-17A inhibition in the MAXIMISE trial [ 59 ]. IL-17 inhibition has shown an acceptable safety profile in RCTs, with nasopharyngitis and local oral fungal infections being commonly reported AEs [ 60 ]. No increase in the incidence of SAEs or in drug discontinuation due to AEs compared with placebo has been identified in these studies.…”

Section: Il-17 Inhibitionmentioning

confidence: 99%

New developments in ankylosing spondylitis—status in 2021

2021

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Axial SpA (axSpA) is a common rheumatic disease characterized by inflammation leading to bone formation and functional impairment. TNF-α and IL-17 represent established targets in axSpA. TNF-α and IL-17 inhibitors have demonstrated efficacy in clinical trials and are currently approved biologic DMARDs for all subsets of the disease. Several lines of evidence implicate a role of an IL-23–IL-17 axis in the disease pathogenesis. In this light, and given the success of IL-17 blockade in axSpA, a similar good response to IL-23 was anticipated. Nevertheless, two clinical trials of anti-IL-23 monoclonal antibodies in axSpA have clearly exhibited negative results. This failure has raised theories for a degree of IL-23 independent pathway. The Janus kinase (JAK) pathway is also a potential therapeutic target, since several cytokines, including those involved in the IL-23–IL-17 axis, signal through the JAK family of tyrosine kinases. Further studies and more extended evaluation of response to cytokine inhibition across different tissues will be required to improve our understanding of SpA pathogenesis and determine its optimal management.

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“…Increasing studies have demonstrated that IL-23/IL-17 axis was highly associated with immune dysfunction and activated autoimmune inflammation [2]. Further studies demonstrated that IL-23/ IL-17 axis contributes to the development of several inflammatory diseases, such as rheumatoid arthritis, psoriasis, psoriatic arthritis, AS, inflammatory bowel disease, sjogren syndrome, multiple sclerosis [14].…”

Section: Discussionmentioning

confidence: 99%

Association of Serum Interleukin-17 and Interleukin-23 Levels with Disease Activity, Function, Mobility, Enthesitis Index in Patients with Ankylosing Spondylitis

Beyazal

Tayfun

Devrimsel

et al. 2022

Aktuelle Rheumatologie

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Aim: More and more studies have demonstrated that the interleukin (IL)-23/IL-17 axis is highly associated with immune dysfunction and activated autoimmune inflammation. The purposes of this study were to determine the serum levels of IL-17 and IL-23 in ankylosing spondylitis (AS) patients compared with healthy controls and evaluate these cytokine levels based on disease-related characteristics. Material and Methods: Eighty-six consecutive AS patients and 70 sex and age-matched healthy controls were included in the study. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Ankylosing Spondylitis Disease Activity Score (ASDAS)-erythrocyte sedimentation rate (ESR), ASDAS-C reactive protein, the Bath Ankylosing Spondylitis Functional Index (BASFI), the Spondyloarthritis Research Consortium of Canada (SPARCC) enthesitis index, the Bath Ankylosing Spondylitis Metrology Index (BASMI), the Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL) and Achilles pain VAS scores were recorded. Serum IL-17 and IL-23 levels were examined by enzyme-linked immunosorbent assay. Results: The serum levels of IL-17, IL-23 and CRP as well as ESR values were significantly increased in AS patients compared with controls (1.94 vs. 0.28 pg/mL p ˂ 0.001; 82.9 vs. 44.3 pg/mL p ˂ 0.001; 0.48 vs. 0.30 mg/dL, p=0.001; 12±13.9 vs. 8±6.8 mm/h, p=0.003, respectively). In AS patients, serum IL-17 levels were significantly correlated with the ASDAS-ESR and ASDAS-CRP (r=0.244, p=0.024; r=0.258, p=0.017), but not with ESR, CRP, BASDAI, function, mobility, quality of life, enthesitis index or Achilles pain scores (all p>0.05). Serum IL-23 levels demonstrated a significant correlation with Achilles pain VAS, but not with other disease-related parameters (all p>0.05). Conclusions: AS patients had increased serum IL-17 and IL-23 levels compared with healthy controls, and serum IL-17 levels were associated with disease activity. Our study results support the hypothesis that the IL17/23 pathway plays an important role in the pathogenesis of AS.

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Efficacy and safety of interleukin-17A inhibitors in patients with ankylosing spondylitis: a systematic review and meta-analysis of randomized controlled trials

Cited by 18 publications

References 58 publications

Safety and Efficacy of Bimekizumab in Patients With Active Ankylosing Spondylitis: Three‐Year Results From a Phase IIb Randomized Controlled Trial and Its Open‐Label Extension Study

Safety and Efficacy of Bimekizumab in Patients With Active Ankylosing Spondylitis: Three‐Year Results From a Phase IIb Randomized Controlled Trial and Its Open‐Label Extension Study

New developments in ankylosing spondylitis—status in 2021

Association of Serum Interleukin-17 and Interleukin-23 Levels with Disease Activity, Function, Mobility, Enthesitis Index in Patients with Ankylosing Spondylitis

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