Raynaud's PhenomenonLife Extension Suggestions
Novel and Emerging Medical Therapies and/or Drug Strategies
Topical Nitrate Therapy
One contribution to Raynaud’s phenomenon appears to stem from changes in the expression of various chemicals produced by the endothelium, particularly the potent vasodilator nitric oxide (NO) (Cooke 2005; Herrick 2011; Herrick 2012). Investigational studies found that applying a topical preparation of nitroglycerin, which enhances nitric oxide signaling, triggers vasodilation (Herrick 2012).
One compound, called Vascana® (MQX-503), combines the proprietary drug-delivery formulation AmphiMatrix (TAM™), which allows drugs to penetrate the skin, with nitroglycerin. As of the time of this writing, the manufacturer is conducting a Phase III trial for final FDA consideration (MediQuest 2008, 2012). Published data demonstrate that this therapy is safe and effective in patients with either primary or secondary Raynaud’s phenomenon (Chung 2009; Hummers 2012). In a 2009 study that enrolled 219 patients with primary and secondary Raynaud’s phenomenon, 212 of whom completed the study, participants applied Vascana® or a placebo just before or up to 5 minutes after a Raynaud’s phenomenon attack. Those receiving the drug (applied as a 0.9% gel) demonstrated an average reduction in the Raynaud’s Condition Score (a standardized assessment) of 14.3%, significantly larger than the 1.3% in the placebo group, but the frequency and duration of the attacks was not statistically different between the two groups. In addition, based on the mean Raynaud’s Condition Score values, patients with systemic sclerosis and secondary Raynaud’s phenomenon improved less (12.3% and 15% improvement, respectively) than those with primary Raynaud’s phenomenon (21.3% improvement). Side effects were similar in the MQX-503 and placebo group (Chung 2009).
Another study on Vascana®, published in December 2012, involved 37 participants with Raynaud’s phenomenon who were treated with 0.5% or 1.25% nitroglycerin gels or with a placebo gel. Both active treatment groups had a greater improvement in blood flow in the fingers than participants receiving placebo (Hummers 2012).
Botulinum Toxin (Botox®)
Used medically to treat muscle spasticity, migraine, and excessive sweating, botulinum toxin is also being evaluated for Raynaud’s phenomenon and other disorders characterized by vasoconstriction. At least 5 studies have been conducted since 2004 in which botulinum toxin A was injected into the fingers and hands. While the studies had multiple limitations, they all demonstrated some improvement in pain and decreased ulceration of the soft tissues. Botulinum toxin A appears to work by multiple mechanisms: it decreases muscular tone, inhibits the release of norepinephrine (a chemical that causes vasoconstriction), and blocks specific receptors involved in cold-induced blood vessel constriction and pain (Iorio 2012). Botox® is available for other indications and may be used “off label” for Raynaud’s phenomenon is some cases under physician supervision.
Endothelin Receptor A Inhibitors
Ambrisentan (Letairis®), FDA-approved to treat pulmonary hypertension, is being evaluated as a vasodilator in patients with scleroderma and Raynaud’s phenomenon. Although a small study that evaluated 18 systemic sclerosis patients did not find any improvements in blood flow to the fingers over 12 weeks, pain and health-related quality of life scores improved (Bena 2011). Other studies have shown some benefit on functional outcomes using the endotelin receptor antagonist bosentan (Tracleer®), but results have been inconsistent (Nguyen 2010; Selenko-Gebauer 2006; Rosato 2010).