To the Editor: Psoriatic arthritis (PsA) is a highly heterogeneous inflammatory arthritis. It occurs in up to 30% of patients with psoriasis and can have severe impacts on peripheral joints, spine, tendon insertions, and fingers.[1] Radiographic progression is currently the preferred method for assessing structural damage of PsA.[2] Biologic treatment options for PsA include tumor necrosis factor-α inhibitors (TNFi), interleukin-12/23 inhibitors, and interleukin-17 (IL-17) inhibitors. The therapeutic effects of IL-17 inhibitors on structural damage were not consistent over multiple trials. Therefore, a systematic review and meta-analysis of the available randomized controlled trials (RCTs) was conducted to quantify the overall effect of IL-17 inhibitors on structural damage in PsA. This study was registered with PROSPERO (No. CRD42022301774).

PubMed, Embase, the Cochrane library, and ClinicalTrials.gov were searched for potentially relevant articles published up to January 20, 2023, and 10 articles were included in the final analysis [Supplementary Figure 1, https://links.lww.com/CM9/B929].[3–12] Quality assessment by the Cochrane Collaboration's Risk of Bias tool showed that all included articles had a low risk of bias [Supplementary Figures 2 and 3, https://links.lww.com/CM9/B929]. The included articles were published between 2016 and 2023, and were derived from four RCTs and their extension studies [Supplementary Table 1, https://links.lww.com/CM9/B929]. The 10 articles involved 2630 patients receiving IL-17 inhibitors, or placebo followed with IL-17 inhibitors, of whom 1709 received IL-17 inhibitors throughout the entire study period while 921 initially received placebo and were switched to IL-17 inhibitors after 16–24 weeks. The mean age of the subjects and the mean disease course of PsA ranged from 48.4 to 50.6 years and 5.6 to 8.2 years, respectively. The percentages of males ranged from 41.6% to 54.1%. The weighted mean age of all the included subjects was 48.9 years and 52.7% were female. All articles included van der Heijde modified total Sharp score (vdH-mTSS) for PsA and the baseline vdH-mTSS ranged from 12.9 to 28.1.

Among those articles with continuous data, four that demonstrated radiographic progression after 24 weeks of treatment were selected for further data analysis. These four articles totaled 2486 patients with radiographic data of vdH-mTSS, including 1636 patients that received IL-17 inhibitors and 850 patients that received placebo. The short-term treatment efficacy of IL-17 inhibitors was evaluated by the mean change from baseline in vdH-mTSS (ΔvdH-mTSS). Visual inspection of funnel plots revealed no evidence of publication bias for the overall pooling of mean ΔvdH-mTSS [Supplementary Figure 4, https://links.lww.com/CM9/B929]. At week 24, the mean ΔvdH-mTSS was lower in patients treated with IL-17 inhibitors than in those treated with placebo (standardized mean difference [SMD] –1.82, 95% CI –3.05 to –0.60, P <0.01) with significant heterogeneity (I2 = 99%; P <0.001; Figure 1A). There was no evidence of asymmetry on the funnel plot for the non-progressors [Supplementary Figure 5, https://links.lww.com/CM9/B929]. At week 24, 1409/1636 (86.1%) of the patients receiving IL-17 inhibitors for PsA were considered radiographic non-progressors compared with 648/850 (76.2%) of the patients receiving placebo (risk ratio [RR] 1.13, 95% CI 1.08 to 1.18, P <0.001), with non-significant heterogeneity (I2 = 0%, P = 0.68; Figure 1B). Therefore, the patients that received IL-17 inhibitors were more likely to experience radiographic non-progression compared with those that received placebo. The data from the mean ΔvdH-mTSS and the proportion of radiographic non-progressors indicated that exposure to IL-17 inhibitors significantly reduced radiographic progression in patients with PsA. The same results were obtained in patients treated with the approved dosages for the treatment of PsA. The mean ΔvdH-mTSS was lower in patients treated with IL-17 inhibitors than in those treated with placebo [SMD –2.52 (95% CI –4.89 to –1.06), P <0.05; Supplementary Figure 6A, https://links.lww.com/CM9/B929]. At week 24, 819/953 (85.9%) of the patients receiving IL-17 inhibitors for PsA were considered radiographic non-progressors compared with 399/520 (76.7%) of the patients receiving placebo [RR 1.12 (95% CI 1.06 to 1.18), P <0.001; Supplementary Figure 6B, https://links.lww.com/CM9/B929]. In addition, a similar result was obtained in patients treated with lower dosage of secukinumab (150 mg Q4W; Supplementary Figure 6C, https://links.lww.com/CM9/B929).

Figure 1:

Forest plots of the short-term and long-term effects of IL-17 inhibitors on retarding radiographic progression. (A) Mean changes in the vdH-mTSS from baseline (ΔvdH-mTSS) with 95% CI for the patients with PsA receiving IL-17 inhibitors vs. placebo at week 24. (B) Relative risk of radiographic non-progressors in PsA patients who received IL-17 inhibitors vs. placebo at week 24. (C) Long-term effects of IL-17 inhibitors on radiographic progression scores in patients with PsA. ΔvdH-mTSS with 95% CI in patients receiving IL-17 inhibitors at year 1. (D) Long-term effects of IL-17 inhibitors on proportion of radiographic non-progressors in patients with PsA. Pooling proportion of non-progressors in patients receiving IL-17 inhibitors at year 1. Radiographic non-progressors were defined as ΔvdH-mTSS of ≤0.5 from baseline. CI: Confidence interval; IV: 10 mg/kg intravenous; IXE: Ixekizumab; LD: Loading dose; M-H: Mantel–Haenszel; PsA: Psoriatic arthritis; SEC: Secukinumab; vdH-mTSS: Van der Heijde modified total Sharp score; ΔvdH-mTSS: Mean change from baseline in vdH-mTSS.

There were no studies of RCTs that directly compared radiographic progression between IL-17 inhibitors and placebos in patients after 1–3 years of treatment. All patients taking placebo were re-randomized to receive IL-17 inhibitors beginning at week 16 for non-responders or beginning at week 24 for responders. Thus, analysis was performed on the data from patients receiving IL-17 inhibitors throughout to quantify the long-term effect of IL-17 inhibitors on radiographic progression. At year 1, the mean ΔvdH-mTSS in PsA patients treated with IL-17 inhibitors was +0.13 (95% CI +0.02 to +0.24) with mild heterogeneity (I2 = 60%, P <0.05; Figure 1C). The mean ΔvdH-mTSS in PsA patients treated with the approved dosages of IL-17 inhibitors was 0.03 (95% CI –0.12 to +0.17; Supplementary Figure S7, https://links.lww.com/CM9/B929). At year 2, the mean ΔvdH-mTSS was +0.48 (95% CI +0.26 to +0.69; Supplementary Figure 8A, https://links.lww.com/CM9/B929). The mean ΔvdH-mTSS in PsA patients treated with the approved dosages of IL-17 inhibitors was +0.35 (95% CI +0.03 to +0.67) (Supplementary Figure 8B, https://links.lww.com/CM9/B929). And only 389 patients completed the 3-year study. At year 3, the mean ΔvdH-mTSS in PsA patients treated with IL-17 inhibitors was +1.45 (95% CI +0.90 to +1.99) (Supplementary Figure 8C, https://links.lww.com/CM9/B929). Among the PsA patients treated with IL-17 inhibitors, the proportion of patients without radiographic progression was 88% (95% CI 86–90%) at year 1 with non-significant heterogeneity (I2 = 22%, P = 0.26; Figures 1D), 84% (95% CI 80–87%) at year 2 [Supplementary Figure 9A, https://links.lww.com/CM9/B929], and 75% (95% CI 71–79%) at year 3 [Supplementary Figure 9B, https://links.lww.com/CM9/B929]. Among the PsA patients treated with the approved dosages of IL-17 inhibitors, the proportion of patients without radiographic progression was 89% (95% CI 85–93%) at year 1 [Supplementary Figure 10A, https://links.lww.com/CM9/B929], 86% (95% CI 80–91%) at year 2 [Supplementary Figure 10B, https://links.lww.com/CM9/B929]. These data from patients taking IL-17 inhibitors over the long term indicated that both the mean ΔvdH-mTSS and the proportion of non-progressors were superior to historical results.[13,14]

This review summarizes the effect of IL-17 inhibitors on structural damage in patients with PsA based on radiographic progression. After 24 weeks, treatment with IL-17 inhibitors leads to better control of radiographic progression than treatment with placebo, as evaluated by both the mean ΔvdH-mTSS and the proportion of patients with radiographic non-progression. Furthermore, IL-17 inhibitors reduced long-term radiographic progression in PsA compared with historical data. Therefore, IL-17 inhibitors suppress radiographic progression in patients with PsA.

Funding

This project was supported by a grant from the National Natural Science Foundation of China (No. 82204722).

Conflicts of interest

None.

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