Sildenafil shows limited effectiveness for Raynaud's phenomenon

On-demand sildenafil outperforms placebo in patients with Raynaud's phenomenon, but the differences are not likely to be clinically relevant, according to a series of n-of-1 trials.

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"Most treatments tested in Raynaud have shown moderate (if any) efficacy, and this is principally due to important heterogeneity," said Dr. Matthieu Roustit of Universite Grenoble Alpes and Grenoble Alpes Hospital, in Grenoble, France.

"The n-of-1 approach seems particularly relevant in this situation to see whether a given patient will benefit from the treatment. On-demand sildenafil could be an option in patients who are not willing to take daily medication," he told Reuters Health by email.

Dr. Roustit and colleagues estimated the efficacy of on-demand sildenafil in treating moderate to severe primary or secondary Raynaud's phenomenon through a series of up to five crossover treatment blocks (sildenafil 40 mg, sildenafil 80 mg, and placebo) in 38 patients who participated in individual n-of-1 trials.

According to the aggregated data, the probability that sildenafil at 40 mg or 80 mg would be more effective than placebo was greater than 90% for all outcomes (except for Raynaud Condition Score with sildenafil 80 mg), the team reports in Annals of Internal Medicine, online October 30.

However, the effect size was modest at best, suggesting the absence of any clinically relevant efficacy when the population as a whole was considered.

There was considerable between-patient heterogeneity regarding efficacy and safety, and there were no significant differences in patient preferences: they favored sildenafil 40 mg in 34% of treatment blocks, sildenafil 80 mg in 35% of treatment blocks, and placebo in 27% of treatment blocks and expressed no preference in 4%.

"In this series of trials we chose the main efficacy outcomes, as it is usually done in standard clinical trials," Dr. Roustit said. "But the next move could be to let patients decide which outcome is the most important for them. They may choose the outcome and the threshold used to define efficacy (eg, a decrease of 30% in the frequency of attacks), before starting the trial. This would be evidence-based, yet personalized, medicine."

Dr. Ariane L. Herrick from the University of Manchester, in the UK, who has studied the diagnosis and management of Raynaud's phenomenon, told Reuters Health by email, "Sildenafil (and other phosphodiesterase type V inhibitors) are being increasingly used in Raynaud's phenomenon (especially in severe secondary Raynaud's) and this study lends some further weight to efficacy at least in some patients. The novel aspect is the 'on-demand' use, which has a good rationale, comparable to the use of sildenafil in erectile dysfunction."

"However," she said, "further studies examining this approach to treatment (including dose-ranging studies and studies in patients with different severities of Raynaud's) are required before this approach to treatment can be widely recommended."

Pfizer France provided financial support and supplied sildenafil and provided grants to 9 of the 15 authors of this report.

—Will Boggs, MD

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