Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Jan 31:28:3.
doi: 10.4103/jrms.jrms_386_22. eCollection 2023.

Effectiveness of bosentan in the treatment of systemic sclerosis-related digital ulcers: Systematic review and meta-analysis

Marziyeh Hosseinbalam  1 , Rasool Nouri  2 , Ziba Farajzadegan  3 , Peyman Mottaghi  1
Affiliations
Review

Effectiveness of bosentan in the treatment of systemic sclerosis-related digital ulcers: Systematic review and meta-analysis

Marziyeh Hosseinbalam et al. J Res Med Sci. .

Abstract

Background: The aim of the present systematic review and meta-analysis was to evaluate the therapeutic efficacy of bosentan, a dual endothelin receptor antagonist, for systemic sclerosis (SSc) patients with digital ulcers (DUs).

Materials and methods: A systematic search of MEDLINE, Embase, Web of Science, and Scopus was done using appropriate keywords till September 2021. Weighted mean difference (WMD) as the effect of therapeutic efficacy of bosentan on continuous outcomes was an estimate. Furthermore, the pooled prevalence of diffuse SSc and limited SSc was computed. Fixed or random effects models when appropriate were used for data synthesis.

Results: Totally, 469 patients, with a mean age ranging from 48.1 to 63.7 years, from 8 studies were included in the systematic review and meta-analysis. The pooled frequency of diffuse SSc and limited SSc was 56% (95% confidence interval [CI]: 39%, 73%) and 44% (95% CI: 27%, 61%). The pooled prevalence of new DUs following bosentan treatment was 21% (95% CI: 10%, 33%). The results of the meta-analysis showed a pooled mean decrease of WMD: -0.09 (95% CI: -0.020, 0.02, P = 0.10), WMD: -2.82 (95% CI: -5.91, 0.27, P = 0.07), and WMD: -6.65 (95% CI: -9.49, -3.82, P < 0.001) in mean SSc-Health Assessment Questionnaire, pain, and Rodnan score, respectively. Our meta-analysis also indicated a significant pooled decrease in the number of new DUs in SSc patients compared to placebo subjects (WMD: -0.89 [95% CI: -1.40, -0.37; P = 0.001]) and baseline values (WMD: -1.34 (95% CI: -1.95, -0.73; P < 0.001).

Conclusion: Bosentan possibly is an efficacious treatment option for SSc-related DUs. Although further large-scale randomized clinical trials are required to confirm the preliminary finding and underlying mechanisms of action.

Keywords: Bosentan; digital ulcer; meta-analysis; systemic sclerosis; treatment.

PubMed Disclaimer

Conflict of interest statement

There are no conflicts of interest.

Figures

Figure 1
Figure 1
Flow diagram of study selection
Figure 2
Figure 2
Forest plot for the frequency of diffuse cutaneous systemic sclerosis (a), Eager's funnel plot asymmetry test for publication bias (b), Forest plot for the frequency of limited cutaneous systemic sclerosis (c), Eager's funnel plot asymmetry test for publication bias (d)
Figure 3
Figure 3
Forest plot of the effect of bosentan treatment on the prevalence of new digital ulcers (a), Eager's funnel plot asymmetry test for publication bias (b)
Figure 4
Figure 4
Forest plot of the effect of bosentan treatment on systemic sclerosis-HAQ score (a), Eager's funnel plot asymmetry test for publication bias (b). HAQ = Health Assessment Questionnaire
Figure 5
Figure 5
Forest plot of the effect of bosentan treatment on pain (a) and Rodnan score (b)
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Matucci-Cerinic M, Kahaleh B, Wigley FM. Review: Evidence that systemic sclerosis is a vascular disease. Arthritis Rheum. 2013;65:1953–62. - PubMed
    1. Amanzi L, Braschi F, Fiori G, Galluccio F, Miniati I, Guiducci S, et al. Digital ulcers in scleroderma: Staging, characteristics and sub-setting through observation of 1614 digital lesions. Rheumatology (Oxford) 2010;49:1374–82. - PubMed
    1. Hachulla E, Clerson P, Launay D, Lambert M, Morell-Dubois S, Queyrel V, et al. Natural history of ischemic digital ulcers in systemic sclerosis: Single-center retrospective longitudinal study. J Rheumatol. 2007;34:2423–30. - PubMed
    1. Mihai C, Landewé R, van der Heijde D, Walker UA, Constantin PI, Gherghe AM, et al. Digital ulcers predict a worse disease course in patients with systemic sclerosis. Ann Rheum Dis. 2016;75:681–6. - PubMed
    1. Meunier P, Dequidt L, Barnetche T, Lazaro E, Duffau P, Richez C, et al. Increased risk of mortality in systemic sclerosis-associated digital ulcers: A systematic review and meta-analysis. J Eur Acad Dermatol Venereol. 2019;33:405–9. - PubMed