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Objectives <p>To evaluate the differences in efficacy and safety between two therapeutic approaches: glucocorticoids monotherapy and combined therapy of glucocorticoids and immunosuppressants, in patients with retroperitoneal fibrosis (RPF).</p> Methods <p>Systematic searches of PubMed, EMBASE, Cochrane Library, Web of Science and ProQuest were performed. Randomized controlled trials, quasi-experimental designs and observational cohort studies that reported the efficacy or recurrence on RPF patients treated with glucocorticoid monotherapy or glucocorticoids combined with specified immunosuppressants therapy were included. Subsequently, a meta-analysis was conducted, followed by an independent bioinformatics analysis to elucidate the mechanisms by which glucocorticoids combined with immunosuppressants potentiate therapeutic effects in the treatment of RPF.</p> Results <p>A total of 11 studies comprising 224 patients were identified. Compared with glucocorticoid monotherapy, combined therapy demonstrated a significant higher response rate (98.9% vs. 85.1%, <i>P </i>= 0.08) and a trend toward more frequent disappearance of hydronephrosis (97.1% vs. 90.0%, <i>P</i> = 0.29). Moreover, while recurrence rates were comparable between the two groups within the first year (5.7% vs. 4.9%, <i>P</i> = 0.92), recurrence in the monotherapy group surpassed that in the combined therapy group beyond 1&#xa0;year of continuous follow-up (10.6% vs. 7.4% at 24&#xa0;months, 21.1% vs. 10.7% at 36&#xa0;months, and 26.1% vs. 12.5% overall), although without significant difference. Bioinformatic analysis revealed that prednisone targets overlapping with RPF-associated genes are mainly involved in acute inflammatory responses and cytokine regulation, whereas immunosuppressants act on a broader range of pathogenic genes implicated in key immunological and fibrotic pathways in RPF. This complementary targeting provides a mechanistic rationale for the role of immunosuppressants in promoting fibrotic tissue remodeling and alleviating mechanical obstruction in RPF. The use of immunosuppressants was associated with a low incidence of adverse events (7.2%), and no severe side effects were reported.</p> Conclusions <p>Clinical evidence from literature and mechanistic insights from bioinformatics both suggest a potential benefit of combination therapy in RPF. However, the evidence remains associative and exploratory. Further randomized controlled trials are warranted to evaluate the potential benefits and risks associated with the addition of immunosuppressants in patients with RPF.</p>

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Glucocorticoid monotherapy vs. immunosuppressant-combined therapy in retroperitoneal fibrosis: clinical evidence and mechanistic insights from bioinformatics

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月8日

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  • Tong Zheng,
  • Zhuoyi Wu,
  • Yishan Ding,
  • Cuiping Pan,
  • Yuexian Shi,
  • Hui Gao

摘要

Objectives

To evaluate the differences in efficacy and safety between two therapeutic approaches: glucocorticoids monotherapy and combined therapy of glucocorticoids and immunosuppressants, in patients with retroperitoneal fibrosis (RPF).

Methods

Systematic searches of PubMed, EMBASE, Cochrane Library, Web of Science and ProQuest were performed. Randomized controlled trials, quasi-experimental designs and observational cohort studies that reported the efficacy or recurrence on RPF patients treated with glucocorticoid monotherapy or glucocorticoids combined with specified immunosuppressants therapy were included. Subsequently, a meta-analysis was conducted, followed by an independent bioinformatics analysis to elucidate the mechanisms by which glucocorticoids combined with immunosuppressants potentiate therapeutic effects in the treatment of RPF.

Results

A total of 11 studies comprising 224 patients were identified. Compared with glucocorticoid monotherapy, combined therapy demonstrated a significant higher response rate (98.9% vs. 85.1%, P = 0.08) and a trend toward more frequent disappearance of hydronephrosis (97.1% vs. 90.0%, P = 0.29). Moreover, while recurrence rates were comparable between the two groups within the first year (5.7% vs. 4.9%, P = 0.92), recurrence in the monotherapy group surpassed that in the combined therapy group beyond 1 year of continuous follow-up (10.6% vs. 7.4% at 24 months, 21.1% vs. 10.7% at 36 months, and 26.1% vs. 12.5% overall), although without significant difference. Bioinformatic analysis revealed that prednisone targets overlapping with RPF-associated genes are mainly involved in acute inflammatory responses and cytokine regulation, whereas immunosuppressants act on a broader range of pathogenic genes implicated in key immunological and fibrotic pathways in RPF. This complementary targeting provides a mechanistic rationale for the role of immunosuppressants in promoting fibrotic tissue remodeling and alleviating mechanical obstruction in RPF. The use of immunosuppressants was associated with a low incidence of adverse events (7.2%), and no severe side effects were reported.

Conclusions

Clinical evidence from literature and mechanistic insights from bioinformatics both suggest a potential benefit of combination therapy in RPF. However, the evidence remains associative and exploratory. Further randomized controlled trials are warranted to evaluate the potential benefits and risks associated with the addition of immunosuppressants in patients with RPF.