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Bosentan treatment for pulmonary arterial hypertension related to connective tissue disease: a subgroup analysis of the pivotal clinical trials and their open-label extensions.
Ann Rheum Dis. 2006 Oct; 65(10):1336-40.AR

Abstract

BACKGROUND

Endothelin-1 is considered to be a central pathogenic factor in connective tissue diseases (CTDs) such as systemic sclerosis (SSc), leading to vasoconstriction, fibrosis, hypertrophy and inflammation. A frequent complication of CTD is pulmonary arterial hypertension (PAH), which has a major effect on functioning and quality of life, and is associated with a particularly poor prognosis.

OBJECTIVE

To present a subgroup analysis that summarises experiences from the pivotal studies and their open-label extensions with the oral dual endothelin-1 receptor antagonist bosentan in patients with PAH and CTD, mostly SSc and lupus erythematosus.

METHODS

66 patients with PAH secondary to CTD, in World Health Organization functional class III or IV, were randomised to two double-blind, placebo-controlled studies and followed up for 12 and 16 weeks, respectively. The primary end point was change in exercise capacity, assessed using the 6-min walk test. In both studies and their extensions, survival was assessed from start of treatment to death or data cut-off and analysed as Kaplan-Meier estimates.

RESULTS

44 patients with PAH secondary to CTD who were treated with bosentan were stable in 6-min walk distance at the end of the study (+19.5 m, 95% confidence interval (CI) -3.2 to 42.2), whereas patients treated with placebo deteriorated (-2.6 m, 95% CI -54.0 to 48.7). 64 patients subsequently received bosentan in an open-label long-term extension study. Mean (standard deviation (SD)) exposure to bosentan was 1.6 (0.9) years, and duration of observation was 1.8 (0.8) years. 8 (16%) patients received epoprostenol as add-on treatment and 7 (14%) after discontinuation of bosentan. Survival in those receiving bosentan was 85.9% after 1 year and 73.4% after 2 years.

CONCLUSION

Short-term bosentan treatment in a subgroup of patients with PAH secondary to CTD seems to have a favourable effect compared with placebo. The long-term follow-up of these patients suggests that first-line bosentan, with the subsequent addition of other PAH treatments if required, is safe for long-term treatment and may have a positive effect on outcome.

Authors+Show Affiliations

Centre for Rheumatology, Royal Free Hospital, Pond Street, London, NW3 2QG, UK. c.denton@medsch.ucl.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16793845

Citation

Denton, C P., et al. "Bosentan Treatment for Pulmonary Arterial Hypertension Related to Connective Tissue Disease: a Subgroup Analysis of the Pivotal Clinical Trials and Their Open-label Extensions." Annals of the Rheumatic Diseases, vol. 65, no. 10, 2006, pp. 1336-40.
Denton CP, Humbert M, Rubin L, et al. Bosentan treatment for pulmonary arterial hypertension related to connective tissue disease: a subgroup analysis of the pivotal clinical trials and their open-label extensions. Ann Rheum Dis. 2006;65(10):1336-40.
Denton, C. P., Humbert, M., Rubin, L., & Black, C. M. (2006). Bosentan treatment for pulmonary arterial hypertension related to connective tissue disease: a subgroup analysis of the pivotal clinical trials and their open-label extensions. Annals of the Rheumatic Diseases, 65(10), 1336-40.
Denton CP, et al. Bosentan Treatment for Pulmonary Arterial Hypertension Related to Connective Tissue Disease: a Subgroup Analysis of the Pivotal Clinical Trials and Their Open-label Extensions. Ann Rheum Dis. 2006;65(10):1336-40. PubMed PMID: 16793845.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Bosentan treatment for pulmonary arterial hypertension related to connective tissue disease: a subgroup analysis of the pivotal clinical trials and their open-label extensions. AU - Denton,C P, AU - Humbert,M, AU - Rubin,L, AU - Black,C M, Y1 - 2006/06/22/ PY - 2006/6/24/pubmed PY - 2006/12/9/medline PY - 2006/6/24/entrez SP - 1336 EP - 40 JF - Annals of the rheumatic diseases JO - Ann. Rheum. Dis. VL - 65 IS - 10 N2 - BACKGROUND: Endothelin-1 is considered to be a central pathogenic factor in connective tissue diseases (CTDs) such as systemic sclerosis (SSc), leading to vasoconstriction, fibrosis, hypertrophy and inflammation. A frequent complication of CTD is pulmonary arterial hypertension (PAH), which has a major effect on functioning and quality of life, and is associated with a particularly poor prognosis. OBJECTIVE: To present a subgroup analysis that summarises experiences from the pivotal studies and their open-label extensions with the oral dual endothelin-1 receptor antagonist bosentan in patients with PAH and CTD, mostly SSc and lupus erythematosus. METHODS: 66 patients with PAH secondary to CTD, in World Health Organization functional class III or IV, were randomised to two double-blind, placebo-controlled studies and followed up for 12 and 16 weeks, respectively. The primary end point was change in exercise capacity, assessed using the 6-min walk test. In both studies and their extensions, survival was assessed from start of treatment to death or data cut-off and analysed as Kaplan-Meier estimates. RESULTS: 44 patients with PAH secondary to CTD who were treated with bosentan were stable in 6-min walk distance at the end of the study (+19.5 m, 95% confidence interval (CI) -3.2 to 42.2), whereas patients treated with placebo deteriorated (-2.6 m, 95% CI -54.0 to 48.7). 64 patients subsequently received bosentan in an open-label long-term extension study. Mean (standard deviation (SD)) exposure to bosentan was 1.6 (0.9) years, and duration of observation was 1.8 (0.8) years. 8 (16%) patients received epoprostenol as add-on treatment and 7 (14%) after discontinuation of bosentan. Survival in those receiving bosentan was 85.9% after 1 year and 73.4% after 2 years. CONCLUSION: Short-term bosentan treatment in a subgroup of patients with PAH secondary to CTD seems to have a favourable effect compared with placebo. The long-term follow-up of these patients suggests that first-line bosentan, with the subsequent addition of other PAH treatments if required, is safe for long-term treatment and may have a positive effect on outcome. SN - 0003-4967 UR - https://www.unboundmedicine.com/medline/citation/16793845/Bosentan_treatment_for_pulmonary_arterial_hypertension_related_to_connective_tissue_disease:_a_subgroup_analysis_of_the_pivotal_clinical_trials_and_their_open_label_extensions_ L2 - https://ard.bmj.com/cgi/pmidlookup?view=long&pmid=16793845 DB - PRIME DP - Unbound Medicine ER -