The Recurrence of Digital Ulcers in Patients with Systemic Sclerosis after Discontinuation of Oral Treprostinil

Ami A Shah; Elena Schiopu; Soumya Chatterjee; Mary Ellen Csuka; Tracy Frech; Avram Goldberg; Robert Spiera; Stanford L Peng; Ryan J McBride; Jody M Cleveland; Virginia Steen

doi:10.3899/jrheum.151437

The Recurrence of Digital Ulcers in Patients with Systemic Sclerosis after Discontinuation of Oral Treprostinil

J Rheumatol. 2016 Sep;43(9):1665-71. doi: 10.3899/jrheum.151437. Epub 2016 Jun 15.

Affiliations

¹ From the Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland; University of Michigan, Ann Arbor, Michigan; Cleveland Clinic, Cleveland, Ohio; Medical College of Wisconsin, Milwaukee, Wisconsin; University of Utah, Salt Lake City, Utah; New York University (NYU) Langone Medical Center, Lake Success; Hospital for Special Surgery, New York, New York; Benaroya Research Institute at Virginia Mason, Seattle, Washington; Georgetown University, Washington, DC; University of North Carolina at Chapel Hill, Chapel Hill; United Therapeutics Corporation, Research Triangle Park, North Carolina, USA.A.A. Shah, MD, MHS, Assistant Professor of Medicine, Director of Clinical and Translational Research, Johns Hopkins Scleroderma Center, Division of Rheumatology, Johns Hopkins University School of Medicine; E. Schiopu, MD, Assistant Professor of Internal Medicine, University of Michigan; S. Chatterjee, MD, Associate Professor of Medicine, Cleveland Clinic; M.E. Csuka, MD, Professor of Medicine, Medical College of Wisconsin; T. Frech, MD, Associate Professor of Medicine, University of Utah; A. Goldberg, MD, Clinical Assistant Professor, NYU Langone Medical Center; R. Spiera, MD, Professor of Clinical Medicine, Hospital for Special Surgery; S.L. Peng, MD, PhD, Vice President, Clinical Development, Benaroya Research Institute at Virginia Mason; R.J. McBride, DrPH, Student, University of North Carolina at Chapel Hill; J.M. Cleveland, MS, Director, Biostatistics, United Therapeutics Corp.; V. Steen, MD, Professor of Medicine, Georgetown University. Ami.Shah@jhmi.edu.
² From the Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland; University of Michigan, Ann Arbor, Michigan; Cleveland Clinic, Cleveland, Ohio; Medical College of Wisconsin, Milwaukee, Wisconsin; University of Utah, Salt Lake City, Utah; New York University (NYU) Langone Medical Center, Lake Success; Hospital for Special Surgery, New York, New York; Benaroya Research Institute at Virginia Mason, Seattle, Washington; Georgetown University, Washington, DC; University of North Carolina at Chapel Hill, Chapel Hill; United Therapeutics Corporation, Research Triangle Park, North Carolina, USA.A.A. Shah, MD, MHS, Assistant Professor of Medicine, Director of Clinical and Translational Research, Johns Hopkins Scleroderma Center, Division of Rheumatology, Johns Hopkins University School of Medicine; E. Schiopu, MD, Assistant Professor of Internal Medicine, University of Michigan; S. Chatterjee, MD, Associate Professor of Medicine, Cleveland Clinic; M.E. Csuka, MD, Professor of Medicine, Medical College of Wisconsin; T. Frech, MD, Associate Professor of Medicine, University of Utah; A. Goldberg, MD, Clinical Assistant Professor, NYU Langone Medical Center; R. Spiera, MD, Professor of Clinical Medicine, Hospital for Special Surgery; S.L. Peng, MD, PhD, Vice President, Clinical Development, Benaroya Research Institute at Virginia Mason; R.J. McBride, DrPH, Student, University of North Carolina at Chapel Hill; J.M. Cleveland, MS, Director, Biostatistics, United Therapeutics Corp.; V. Steen, MD, Professor of Medicine, Georgetown University.

PMID: 27307535
DOI: 10.3899/jrheum.151437

Abstract

Objective: Prior studies investigating the efficacy of oral treprostinil to treat digital ulcers (DU) in systemic sclerosis (SSc)-associated Raynaud phenomenon have yielded conflicting results. In this investigation, we examined whether DU burden increased after patients withdrew from oral treprostinil that was administered during an open-label extension study.

Methods: A multicenter, retrospective study was conducted to determine DU burden in the year after withdrawal from oral treprostinil. DU burden 3-6 months (Time A) and > 6-12 months (Time B) after drug withdrawal was compared with DU burden at baseline, defined as the last day receiving drug in the open-label extension study, by a paired Student t test. Changes in DU burden while receiving drug in the open-label study were compared with changes in DU burden at Time B by a paired Student t test.

Results: Fifty-one patients from 9 clinical sites were included for analysis. DU burden increased significantly from baseline (mean 0.47) to Time A (mean 2.1, p = 0.002, n = 23) and Time B (mean 1.45, p = 0.013, n = 30). Total DU burden decreased during oral treprostinil exposure (mean change -0.6) and then increased by Time B (mean change 1.05, p = 0.0027 for comparison, n = 30). In the year after drug withdrawal, many patients required vasodilator therapy and pain medications. Three patients were hospitalized for complications from DU, and 4 patients required surgery for DU.

Conclusion: Total DU burden increased significantly after discontinuation of oral treprostinil. These data provide supportive evidence of a beneficial effect of oral treprostinil for the vascular complications of SSc and suggest that further study is warranted.

Keywords: DIGITAL ULCERS; RAYNAUD PHENOMENON; SYSTEMIC SCLEROSIS; TREPROSTINIL DIOLAMINE.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Antihypertensive Agents / therapeutic use*
Epoprostenol / analogs & derivatives*
Epoprostenol / therapeutic use
Female
Fingers / blood supply*
Humans
Male
Middle Aged
Raynaud Disease / drug therapy*
Raynaud Disease / etiology
Recurrence
Retrospective Studies
Scleroderma, Systemic / complications*
Skin Ulcer / drug therapy*
Skin Ulcer / etiology

Substances

Antihypertensive Agents
Epoprostenol
treprostinil