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.

Trial registration: ClinicalTrials.gov NCT02165111 NCT02165111.

Figure 1

Sites of injection and dose.

Figure 2

Figure 2A (top): Change in blood perfusion (measured with LDI scanner) by treatment arm over time. Presented as means and standard deviation bars. Figure 2B (bottom): Change in blood perfusion (measured with LDI scanner) over time by type of scleroderma. Presented as means and standard deviation bars.

Figure 2

Figure 2A (top): Change in blood perfusion (measured with LDI scanner) by treatment arm over time. Presented as means and standard deviation bars. Figure 2B (bottom): Change in blood perfusion (measured with LDI scanner) over time by type of scleroderma. Presented as means and standard deviation bars.

Figure 3

Figure 3A (left): Observed Raynaud's Condition Score throughout study period. Presented as means and standard deviation bars. Figure 3B (right): Fitted Raynaud's Condition Score measurements throughout study period (unadjusted). Presented as mean rates of decline by study group.

Figure 3

Figure 3A (left): Observed Raynaud's Condition Score throughout study period. Presented as means and standard deviation bars. Figure 3B (right): Fitted Raynaud's Condition Score measurements throughout study period (unadjusted). Presented as mean rates of decline by study group.