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 with 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 (ClinicalTrials.gov #NCT02165111), patients with scleroderma-associated RP received Btx-A (50 units in 2.5 mL) in one randomly selected hand and sterile saline (2.5 mL) in the opposite hand. Follow-up at 1 and 4 months post-injection included Laser Doppler Imaging (LDI) of hands, patient-reported outcomes, and physical exam. We compared outcomes using paired t-test and population average generalized models with generalized estimating equations. Results Of 40 patients enrolled, 25 had limited and 15 diffuse scleroderma. From baseline to 1-month follow-up, there was a greater reduction in average blood flow in Btx-A hands compared to placebo. The model estimated that this difference was statistically significant (average difference: -30.08 flux units, 95% CI: -56.19 to -3.98, p-value=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 improved slightly for Btx-A hands in QuickDASH, McCabe score, pain VAS, and Raynaud's Condition Score. Conclusion Our laboratory-based LDI flow data do not support using Btx-A to treat RP in all scleroderma patients. The secondary clinical outcomes suggest some positive, but questionably clinically meaningful effect. The role of Btx-A in treating RP should be further studied with more homogeneous patient populations and in unique clinical situations like acute digital ischemia.

Optimisation of botulinum toxin type a treatment for the management of Raynaud’s phenomenon using a dorsal approach: a prospective case series

“…One other study has investigated the effect of Btx-A injected via a dorsal approach [24]. Bello et al performed a randomised double-blind placebo controlled clinical trial in patients with scleroderma associate RP using Btx-A in one randomly selected hand and sterile saline in the opposite hand [24]. This study followed 40 patients for 1 and 4 months post injection using laser Doppler imaging, patient-reported outcomes and physical exam.…”

Successful treatment of Raynaud's phenomenon and digital ulcers in systemic sclerosis patients with botulinum toxin B injection: Assessment of peripheral vascular disorder by angiography and dermoscopic image of nail fold capillary

“…9 However, a randomized, placebocontrolled, double-blind clinical trial conducted on 40 patients with SSc has shown that BTX-A did not significantly improve blood flow to the hands of patients with SSc-associated RP, but that patient-reported severity of RP showed a statistically significant improvement in hands treated using BTX-A. 12 In this randomized study, it was suggested that the negative results might have been due to the screening methods, which allowed for the inclusion of patients with large vessel disease, such as radial or ulnar artery occlusion. 12 In addition, BTX-A was injected into the web space on the dorsal surface of the hand to prevent hand weakness.…”

“…12 In this randomized study, it was suggested that the negative results might have been due to the screening methods, which allowed for the inclusion of patients with large vessel disease, such as radial or ulnar artery occlusion. 12 In addition, BTX-A was injected into the web space on the dorsal surface of the hand to prevent hand weakness. 12 A more distal injection site was used in this randomized study than that reported in some previous studies, including in our reports.…”

“…12 In addition, BTX-A was injected into the web space on the dorsal surface of the hand to prevent hand weakness. 12 A more distal injection site was used in this randomized study than that reported in some previous studies, including in our reports. 9,10 In our previous 9,10 and present study, BTX was s.c. injected just proximal to the A1 pulley (the space next to the metacarpophalangeal joint), targeting the neurovascular bundles from the palmar aspect.…”

The novel use of botulinum toxin A for the treatment of Raynaud’s phenomenon in the toes

“…It has shown promise as a therapeutic option for patients with severe RP in the fingers that is refractory to other treatments 2 3. However, overall evidence conflicting and further randomised controlled trials (RCTs) are needed if Btx-A is to become a viable treatment option 5. Furthermore, there are currently no studies in the literature that report the use of Btx-A for the treatment of RP in the toes.…”