Efficacy and safety of IL-23 inhibitors in the treatment of psoriatic arthritis: a meta-analysis based on randomized controlled trials

Huang, Xiaojing; Shentu, Haojie; He, Yujing; Lai, Haijia; Xu, Chen; Chen, Mei‐Ling; Zhu, Haowei

doi:10.1007/s12026-023-09366-4

Cited by 16 publications

(12 citation statements)

References 42 publications

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“…In terms of safety, our data are in line with pooled data from reSURFACE trials, from tildrakizumab real-world studies and safety data from other IL-23 studies with a low incidence of infections, with minimal severe outcomes and the absence of other adverse effects such as major cardiovascular events, cancer, inflammatory bowel disease or candida infection. 13 , 32 – 34 …”

Section: Discussionmentioning

confidence: 99%

Tildrakizumab for the treatment of moderate-to-severe psoriasis: a 52-week, real-world Portuguese multicentric study

Torres,

Varela,

Mendes Bastos

et al. 2024

DIC

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Background Real-world evidence plays a pivotal role in validating the efficacy of biologic drugs beyond the controlled environment of randomized trials. This study aimed to evaluate the effectiveness of tildrakizumab in treating moderate-to-severe psoriasis within a real-world setting over a 52-week period in Portugal. Methods This multicentric, prospective, observational study included adult patients with moderate-to-severe psoriasis. All participants received tildrakizumab 100 mg at weeks 0 and 4, followed by a maintenance dose every 12 weeks, and were monitored for 52 weeks. Primary endpoints were determined based on Psoriasis Area and Severity Index (PASI) assessments at baseline, 16 (±2) weeks, 28 (±2) weeks and 52 (±2) weeks. Results A total of 54 patients were enrolled in the study (56% men, mean age of 50.3 ± 14.4 years). Half of the sample ( n =27) had no prior experience with biologic treatments. About 74% of patients ( n =40) presented at least one comorbidity during the study, with psoriatic arthritis being the most prevalent (29.6%). By week 52, there was a significant decrease in the mean PASI from 17.8±10.3 at baseline to 1.3±1.9 ( p <0.001), indicating an overall improvement of 93%. By week 52, more than 85% of patients attained PASI ≤5, more than 80% reached PASI ≤3, and nearly 60% achieved PASI ≤1. Infections were observed in 9.3% of patients, and one patient required hospitalization (1.9%). The cumulative proportion of patients continuing treatment at 52 weeks was 88.9%. Conclusions This study demonstrates that tildrakizumab is an effective and safe agent for the treatment of moderate-to-severe psoriasis in a diverse, real-world setting.

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Section: Discussionmentioning

confidence: 99%

Tildrakizumab for the treatment of moderate-to-severe psoriasis: a 52-week, real-world Portuguese multicentric study

Torres,

Varela,

Mendes Bastos

et al. 2024

DIC

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“…Thus, the consequences of IL-23 inhibition may be organ specific. This warrants the study of IL-23 antagonists in other tissues targeted by these drugs (e.g., the intestinal mucosa ( 27 ) and the synovium ( 28 )).…”

Section: Discussionmentioning

confidence: 99%

Single-cell analysis of psoriasis resolution reveals an inflammatory fibroblast state targeted by IL-23 blockade

Francis,

McCluskey,

Ganier

et al. 2023

Preprint

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Biologic drugs targeting the IL-23/IL-17 axis have transformed outcomes for people living with psoriasis, allowing most patients to achieve skin clearance. Despite the potential to reveal fundamental regulators of skin homeostasis, the early mechanisms of action of these drugs remain poorly understood. Here, we performed longitudinal single-cell RNA sequencing in individuals with psoriasis who had been successfully treated with IL-23 inhibitor therapy. By profiling skin at baseline, day 3 and day 14 of treatment, we demonstrated that IL-23 blockade causes marked gene expression shifts, with fibroblast and myeloid populations displaying the most extensive changes at day 3. We identified a transientWNT5A+/IL24+fibroblast state, which was only detectable in lesional skin. The study of ligand-receptor interactions revealed that pro-inflammatory signals stemming from theseWNT5A+/IL24+fibroblasts upregulated multiple genes in differentiated keratinocytes. Importantly, the abundance ofWNT5A+/IL24+fibroblasts was significantly reduced after treatment. This observation was validatedin-silico, by deconvolution of multiple transcriptomic datasets, and experimentally, by RNAin situhybridization of additional skin samples. These findings demonstrate that the evolution of inflammatory fibroblast states is a key feature of resolving psoriasis skin.

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“…[25][26][27][28] Biologics targeting IL-23p19 and IL-12/23p40 subunits have been con rmed to be effective in the treatment of psoriasis and psoriatic arthritis. [29][30][31]IL-23 is a member of the IL-12 cytokine family and consists of the IL-23p19 subunit and the IL-12/23p40 subunit, which is shared with IL-12. [32] Ustekinumab speci cally blocks the IL-12/23 subunit p40 in CD patients whereas risankizumab, brazikumab, guselkumab and mirikizumab selectively block the unique subunit p19.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of IL-23 inhibitors and IL-12/23 inhibitors in the induction treatment of Crohn's disease: a meta-analysis based on randomized controlled trials

Guo,

Shentu,

Sha

et al. 2023

Preprint

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Background A growing number of randomized controlled trials (RCTs) have demonstrated interleukin (IL)-23 and IL-12/23 inhibitors effectiveness in treating Crohn's disease (CD). This study evaluated the efficacy of IL-23 and IL-12/23 inhibitors in the induction phase for the treatment of CD. Methods We searched the following databases from inception until December, 2022: Medline, Embase, Web of Science and the Cochrane Library. The primary outcome was the proportion of CD patients who achieved clinical remission at the end of the induction therapy period. Secondary outcomes included clinical response, endoscopic remission, endoscopic response and normalized C-reactive protein (CRP). Results After screening, 7 RCTs were included in our study. The meta-analysis showed that, in the induction period, more patients treated with IL-23 inhibitors and IL-12/23 inhibitors achieved clinical remission than patients with placebo therapy (RR = 2.11; 95%CI: 1.83–2.44; RR = 1.94; 95%CI: 1.64–2.29; respectively). The IL-23 inhibitor group and the IL-12/23 inhibitor group showed higher clinical response rates than the placebo group (RR = 1.92; 95%CI: 1.74-2,11; RR = 1.83; 95%CI: 1.61–2.09; respectively). In addition, IL-23 inhibitor group had higher endoscopic remission rate and endoscopic response rate than placebo group, the corresponding pooled RR were 3.40 (95%CI: 2.57–4.50) and 2.65 (95%CI: 2.65–3.12), respectively. Conclusions IL-23 and IL-12/23 inhibitors were efficiency methods in the induction treatment of CD.

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Efficacy and safety of IL-23 inhibitors in the treatment of psoriatic arthritis: a meta-analysis based on randomized controlled trials

Cited by 16 publications

References 42 publications

Tildrakizumab for the treatment of moderate-to-severe psoriasis: a 52-week, real-world Portuguese multicentric study

Tildrakizumab for the treatment of moderate-to-severe psoriasis: a 52-week, real-world Portuguese multicentric study

Single-cell analysis of psoriasis resolution reveals an inflammatory fibroblast state targeted by IL-23 blockade

Efficacy of IL-23 inhibitors and IL-12/23 inhibitors in the induction treatment of Crohn's disease: a meta-analysis based on randomized controlled trials

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