The Therapeutic Efficacy of Botulinum Toxin in Treating Scleroderma-Associated Raynaud's Phenomenon: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Ricardo J. Bello, Carisa Miller Cooney, Eitan Melamed, Keith Follmar, Gayane Yenokyan, Gwendolyn Leatherman, Ami Shah, Fredrick Wigley, Laura Hummers, Scott Lifchez

Research output: Contribution to journalArticle

Abstract

Objective: To assess the therapeutic efficacy of local injections of botulinum toxin type A (Btx-A) in improving blood flow to the hands of patients with Raynaud's phenomenon (RP) secondary to scleroderma. Methods: In this randomized, double-blind, placebo-controlled clinical trial, patients with scleroderma-associated RP received Btx-A (50 units in 2.5 ml sterile saline) in one randomly selected hand and sterile saline (2.5 ml) in the opposite hand. Follow-up at 1 and 4 months postinjection included laser Doppler imaging of hands, patient-reported outcomes, and physical examination. We compared outcomes using paired t-tests and population-average generalized models with generalized estimating equations. Results: Of 40 patients enrolled, 25 had limited scleroderma and 15 had diffuse scleroderma. From baseline to 1-month follow-up, there was a greater reduction in average blood flow in Btx-A–treated hands compared to placebo-treated hands. The model estimated that this difference was statistically significant (average difference −30.08 flux units [95% confidence interval −56.19, −3.98], P for interaction = 0.024). This difference was mainly influenced by patients with longstanding RP and diffuse scleroderma. Change in blood flow at 4-month follow-up was not significantly different between groups. Clinical measures (QuickDASH, McCabe Cold Sensitivity Score, pain on a visual analog scale, and Raynaud's Condition Score) improved slightly for Btx-A–treated hands. Conclusion: Our laboratory-based laser Doppler imaging flow data do not support using Btx-A to treat RP in all scleroderma patients. The secondary clinical outcomes suggest some positive effect, but its clinical meaningfulness is questionable. The role of Btx-A in treating RP should be further studied with more homogeneous patient populations and in unique clinical situations such as acute digital ischemia.

Original languageEnglish (US)
Pages (from-to)1661-1669
Number of pages9
JournalArthritis and Rheumatology
Volume69
Issue number8
DOIs
StatePublished - Aug 1 2017

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Raynaud Disease
Botulinum Toxins
Controlled Clinical Trials
Hand
Placebos
Type A Botulinum Toxins
Diffuse Scleroderma
Therapeutics
Limited Scleroderma
Lasers
Visual Analog Scale
Population
Physical Examination
Ischemia
Confidence Intervals
Pain
Injections

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology

Cite this

@article{e504a18616e042f9bdacad14ee3bcf74,
title = "The Therapeutic Efficacy of Botulinum Toxin in Treating Scleroderma-Associated Raynaud's Phenomenon: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial",
abstract = "Objective: To assess the therapeutic efficacy of local injections of botulinum toxin type A (Btx-A) in improving blood flow to the hands of patients with Raynaud's phenomenon (RP) secondary to scleroderma. Methods: In this randomized, double-blind, placebo-controlled clinical trial, patients with scleroderma-associated RP received Btx-A (50 units in 2.5 ml sterile saline) in one randomly selected hand and sterile saline (2.5 ml) in the opposite hand. Follow-up at 1 and 4 months postinjection included laser Doppler imaging of hands, patient-reported outcomes, and physical examination. We compared outcomes using paired t-tests and population-average generalized models with generalized estimating equations. Results: Of 40 patients enrolled, 25 had limited scleroderma and 15 had diffuse scleroderma. From baseline to 1-month follow-up, there was a greater reduction in average blood flow in Btx-A–treated hands compared to placebo-treated hands. The model estimated that this difference was statistically significant (average difference −30.08 flux units [95{\%} confidence interval −56.19, −3.98], P for interaction = 0.024). This difference was mainly influenced by patients with longstanding RP and diffuse scleroderma. Change in blood flow at 4-month follow-up was not significantly different between groups. Clinical measures (QuickDASH, McCabe Cold Sensitivity Score, pain on a visual analog scale, and Raynaud's Condition Score) improved slightly for Btx-A–treated hands. Conclusion: Our laboratory-based laser Doppler imaging flow data do not support using Btx-A to treat RP in all scleroderma patients. The secondary clinical outcomes suggest some positive effect, but its clinical meaningfulness is questionable. The role of Btx-A in treating RP should be further studied with more homogeneous patient populations and in unique clinical situations such as acute digital ischemia.",
author = "Bello, {Ricardo J.} and Cooney, {Carisa Miller} and Eitan Melamed and Keith Follmar and Gayane Yenokyan and Gwendolyn Leatherman and Ami Shah and Fredrick Wigley and Laura Hummers and Scott Lifchez",
year = "2017",
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volume = "69",
pages = "1661--1669",
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T1 - The Therapeutic Efficacy of Botulinum Toxin in Treating Scleroderma-Associated Raynaud's Phenomenon

T2 - A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

AU - Bello, Ricardo J.

AU - Cooney, Carisa Miller

AU - Melamed, Eitan

AU - Follmar, Keith

AU - Yenokyan, Gayane

AU - Leatherman, Gwendolyn

AU - Shah, Ami

AU - Wigley, Fredrick

AU - Hummers, Laura

AU - Lifchez, Scott

PY - 2017/8/1

Y1 - 2017/8/1

N2 - Objective: To assess the therapeutic efficacy of local injections of botulinum toxin type A (Btx-A) in improving blood flow to the hands of patients with Raynaud's phenomenon (RP) secondary to scleroderma. Methods: In this randomized, double-blind, placebo-controlled clinical trial, patients with scleroderma-associated RP received Btx-A (50 units in 2.5 ml sterile saline) in one randomly selected hand and sterile saline (2.5 ml) in the opposite hand. Follow-up at 1 and 4 months postinjection included laser Doppler imaging of hands, patient-reported outcomes, and physical examination. We compared outcomes using paired t-tests and population-average generalized models with generalized estimating equations. Results: Of 40 patients enrolled, 25 had limited scleroderma and 15 had diffuse scleroderma. From baseline to 1-month follow-up, there was a greater reduction in average blood flow in Btx-A–treated hands compared to placebo-treated hands. The model estimated that this difference was statistically significant (average difference −30.08 flux units [95% confidence interval −56.19, −3.98], P for interaction = 0.024). This difference was mainly influenced by patients with longstanding RP and diffuse scleroderma. Change in blood flow at 4-month follow-up was not significantly different between groups. Clinical measures (QuickDASH, McCabe Cold Sensitivity Score, pain on a visual analog scale, and Raynaud's Condition Score) improved slightly for Btx-A–treated hands. Conclusion: Our laboratory-based laser Doppler imaging flow data do not support using Btx-A to treat RP in all scleroderma patients. The secondary clinical outcomes suggest some positive effect, but its clinical meaningfulness is questionable. The role of Btx-A in treating RP should be further studied with more homogeneous patient populations and in unique clinical situations such as acute digital ischemia.

AB - Objective: To assess the therapeutic efficacy of local injections of botulinum toxin type A (Btx-A) in improving blood flow to the hands of patients with Raynaud's phenomenon (RP) secondary to scleroderma. Methods: In this randomized, double-blind, placebo-controlled clinical trial, patients with scleroderma-associated RP received Btx-A (50 units in 2.5 ml sterile saline) in one randomly selected hand and sterile saline (2.5 ml) in the opposite hand. Follow-up at 1 and 4 months postinjection included laser Doppler imaging of hands, patient-reported outcomes, and physical examination. We compared outcomes using paired t-tests and population-average generalized models with generalized estimating equations. Results: Of 40 patients enrolled, 25 had limited scleroderma and 15 had diffuse scleroderma. From baseline to 1-month follow-up, there was a greater reduction in average blood flow in Btx-A–treated hands compared to placebo-treated hands. The model estimated that this difference was statistically significant (average difference −30.08 flux units [95% confidence interval −56.19, −3.98], P for interaction = 0.024). This difference was mainly influenced by patients with longstanding RP and diffuse scleroderma. Change in blood flow at 4-month follow-up was not significantly different between groups. Clinical measures (QuickDASH, McCabe Cold Sensitivity Score, pain on a visual analog scale, and Raynaud's Condition Score) improved slightly for Btx-A–treated hands. Conclusion: Our laboratory-based laser Doppler imaging flow data do not support using Btx-A to treat RP in all scleroderma patients. The secondary clinical outcomes suggest some positive effect, but its clinical meaningfulness is questionable. The role of Btx-A in treating RP should be further studied with more homogeneous patient populations and in unique clinical situations such as acute digital ischemia.

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