Adverse Events Associated With Anti-IL-23 Agents: Clinical Evidence and Possible Mechanisms

Ru, Yi; Ding, Xiaojie; Luo, Ying; Li, Hongjin; Sun, Xiaoying; Zhou, Mi; Zhou, Yajun; Kuai, Le; Xing, Meng; Liu, Liu; Luo, Yue; Song, Jiankun; Chen, Jiale; B, Li; Li, Xin

doi:10.3389/fimmu.2021.670398

Cited by 22 publications

(12 citation statements)

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“…Compared with traditional therapies, although biological agents have good curative effects, the risk of recurrence is increased. A recently published meta-analysis showed that anti-IL-23 drugs are likely to cause a series of immunological and non-immunological adverse events, while their long-term use may cause mental illness ( 8 ). Therefore, dermatologists are always seeking better treatment options.…”

Section: Introductionmentioning

confidence: 99%

Sphingosine-1-Phosphate and Its Signal Modulators Alleviate Psoriasis-Like Dermatitis: Preclinical and Clinical Evidence and Possible Mechanisms

Liu

Wang

Li³

et al. 2021

Front. Immunol.

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BackgroundPsoriasis is an autoimmune skin disease associated with lipid metabolism. Sphingosine-1-phosphate (S1P) is a bioactive lipid that plays a key role in the development of autoimmune diseases. However, there is currently a lack of comprehensive evidence of the effectiveness of S1P on psoriasis.ObjectiveTo assess the efficacy and possible mechanism of S1P and its signal modulators in the treatment of psoriasis-like dermatitis.MethodsSix databases were searched through May 8, 2021, for studies reporting S1P and its signal modulators. Two reviewers independently extracted information from the enrolled studies. Methodological quality was assessed using SYRCLE’s risk of bias tool. RevMan 5.3 software was used to analyze the data. For clinical studies, the Psoriasis Area and Severity Index score were the main outcomes. For preclinical studies, we clarified the role of S1P and its regulators in psoriasis in terms of phenotype and mechanism.ResultsOne randomized double-blind placebo-controlled trial and nine animal studies were included in this study. The pooled results showed that compared with control treatment, S1P receptor agonists [mean difference (MD): −6.80; 95% confidence interval (CI): −8.23 to −5.38; p<0.00001], and sphingosine kinase 2 inhibitors (MD: −0.95; 95% CI: −1.26 to −0.65; p<0.00001) alleviated psoriasis-like dermatitis in mice. The mechanism of S1P receptor agonists in treating psoriasis might be related to a decrease in the number of white blood cells, topical lymph node weight, interleukin-23 mRNA levels, and percentage of CD3+ T cells (p<0.05). Sphingosine kinase 2 inhibitors ameliorated psoriasis in mice, possibly by reducing spleen weight and cell numbers (p<0.05).ConclusionsS1P receptor agonists and sphingosine kinase 2 inhibitors could be potential methods for treating psoriasis by decreasing immune responses and inflammatory factors.

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Section: Introductionmentioning

confidence: 99%

Sphingosine-1-Phosphate and Its Signal Modulators Alleviate Psoriasis-Like Dermatitis: Preclinical and Clinical Evidence and Possible Mechanisms

Liu

Wang

Li³

et al. 2021

Front. Immunol.

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“…Anti-IL-23 agents are widely used to treat various autoimmune conditions like CD, ulcerative colitis, psoriasis and ankylosing spondylitis. Compared with anti-IL-23-p19 agents, anti-IL12/23-p40 agents are associated with more adverse effects and more frequently lead to cardiovascular events 22. Although the relationship between anti-IL-12/23-p40 agents and SCEs remains unclear, this rare case of HF after initiation of ustekinumab serves as an important data point in determining that relationship; clinicians should consider this in the differential while this relationship continues to be explored.…”

Section: Discussionmentioning

confidence: 98%

Heart failure associated with ustekinumab therapy for treatment of Crohn’s Disease

Morgenweck

Park²,

Bower³

2022

BMJ Case Rep

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A man in his 60s with penetrating ileocolonic Crohn’s disease (CD), recently started on ustekinumab therapy, presented with new onset dyspnoea, paroxysmal nocturnal dyspnoea and dependent oedema. He was diagnosed with heart failure (HF) 10 months after starting ustekinumab therapy. His symptoms resolved with discontinuation of ustekinumab and he had recovery of his cardiac function. Though initial studies that led to the U.S Food and Drug Administration (FDA)approval for ustekinumab did not detect a signal for HF, postmarketing surveillance has detected rare cases of HF after initiation of the medication. This is one of the few reported cases of HF associated with ustekinumab therapy for CD.

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“…BAs are highly active immunologic agents that exert their effects by blocking specific inflammatory factors produced by the immune system. BAs are commonly used in the treatment of autoimmune diseases such as rheumatoid arthritis, PSA, systemic lupus erythematosus, and ankylosing spondylitis ( 5 ). In 2004, the European Medicines Agency (EMA) approved the first BA, etanercept; adalimumab and ustekinumab have since emerged ( 6 ).…”

Section: Introductionmentioning

confidence: 99%

Adverse events associated with anti-IL-17 agents for psoriasis and psoriatic arthritis: a systematic scoping review

Wang

Liu

et al. 2023

Front. Immunol.

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BackgroundAnti-interleukin (IL)-17 biological agents (BAs) have significant efficacy in the treatment of psoriasis and psoriatic arthritis; however, adverse events (AEs) are common, and their safety has not been systematically evaluated.ObjectivesThe purpose of this systematic review and meta-analysis was to summarize the number and corresponding rates of AEs caused by anti-IL-17 BAs in patients with psoriasis and psoriatic arthritis to improve clinical decision-making regarding their use.MethodsPubMed, Embase, Cochrane Library, and Web of Science databases were independently searched by three authors for articles on the treatment of psoriasis with anti-IL-17 BAs that were published before March 1, 2022, and included at least one AE. Dichotomous variables and 95% confidence intervals (CI) were analyzed using R software (version 4.1.3) and the Meta and Metafor software packages. Funnel plots and meta-regression were used to test for the risk of bias, I2 was used to assess the magnitude of heterogeneity, and subgroup analysis was used to reduce heterogeneity.ResultsA total of 57 studies involving 28,424 patients with psoriasis treated with anti-IL-17 BAs were included in the meta-analysis. Subgroup analysis showed that anti-IL-17A (73.48%) and anti-IL-17A/F (73.12%) BAs were more likely to cause AEs than anti-IL-17R BAs (65.66%). The incidence of AEs was as high as 72.70% with treatment durations longer than one year, and long-term use of medication had the potential to lead to mental disorders. Infection (33.16%), nasopharyngitis (13.74%), and injection site reactions (8.28%) were the most common AEs. Anti-IL-17 BAs were most likely to cause type α (33.52%) AEs. Type δ AEs (1.01%) were rarely observed.ConclusionsAnti-IL-17 BAs used for the treatment of psoriasis and psoriatic arthritis caused a series of AEs, but the symptoms were generally mild.

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Adverse Events Associated With Anti-IL-23 Agents: Clinical Evidence and Possible Mechanisms

Cited by 22 publications

References 71 publications

Sphingosine-1-Phosphate and Its Signal Modulators Alleviate Psoriasis-Like Dermatitis: Preclinical and Clinical Evidence and Possible Mechanisms

Sphingosine-1-Phosphate and Its Signal Modulators Alleviate Psoriasis-Like Dermatitis: Preclinical and Clinical Evidence and Possible Mechanisms

Heart failure associated with ustekinumab therapy for treatment of Crohn’s Disease

Adverse events associated with anti-IL-17 agents for psoriasis and psoriatic arthritis: a systematic scoping review

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