October 27, 2008 (San Francisco, California) — In the first randomized controlled trial of its kind, the drug tadalafil reduced the duration and frequency of secondary Raynaud’s phenomenon episodes in patients with scleroderma and mixed connective-tissue disease. It also decreased the incidence of ischemic ulcers when used with other treatments, according to research presented here at the American College of Rheumatology 2008 Annual Scientific Meeting.

“Tadalafil is a promising agent in the management of patients with secondary Raynaud’s phenomenon, particularly patients who do not respond to conventional vasodilators,” said first author Padmanabha Shenoy, MD, senior resident at the Sanjay Gandhi Post Graduate Institute of Medical Science, in Lucknow, India.

“Unfortunately, current therapy for secondary Raynaud’s phenomenon is suboptimal and challenging to the clinician, as there are limited drugs to treat it,” Dr. Shenoy told the meeting attendees. Although secondary Raynaud’s phenomenon affects less than 1% of the population, it can be quite serious when it occurs, resulting in ischemia and ulcers, he said.

The researchers also suggested that the therapy might provide hope for the treatment of scleroderma, specifically to reverse the narrowing of blood vessels seen in the lungs and hearts of patients. “The study does show that tadalafil improves blood flow to the hands. But we need longer and larger studies to test whether tadalafil might also improve survival in scleroderma patients,” Dr. Shenoy told Medscape Rheumatology.

Of the 25 patients studied, all were receiving calcium channel blockers and 18 were also taking other vasodilators. All were resistant to conventional vasodilators, and were experiencing more than 4 Raynaud’s episodes per week. They were randomly assigned to receive either 20 mg of tadalafil or placebo every other day for 6 weeks. After a washout period of 7 days, patients switched treatments for another 6 weeks.

The results indicated a significant decrease in the frequency and duration of Raynaud’s episodes and a striking improvement in the incidence and healing of ulcers. Patients taking tadalafil experienced fewer Raynaud’s episodes than those taking placebo (2.23 vs 3.36), and the episodes were also of shorter duration (31.5 minutes vs 53.9 minutes). One patient experienced a complete resolution of Raynaud’s phenomenon.

All of the 24 fingertip ulcers present at the start of treatment healed during tadalafil treatment, compared with 3 of 13 in the placebo group. Only 1 new fingertip ulcer was reported in the tadalafil group, compared with 13 new ulcers in the placebo group.

There were no serious adverse events associated with tadalafil. One patient withdrew from the study because of a persistent nonpainful erection after the first dose of tadalafil.

Patient global assessment, physician global assessment, and the effect of Raynaud’s phenomenon and fingertip ulcers on activities of daily living, as assessed by the Scleroderma Health Assessment Questionnaire, also improved significantly for patients taking tadalafil, according to Dr. Shenoy. “It improved functional outcomes as well as endothelial function,” he said.

“These are very exciting data, because the effects on Raynaud’s were much more dramatic than those seen in previous studies,” said Leslie J. Crofford, MD, chief of the division of rheumatology at the University of Kentucky, in Lexington, and president of the American College of Rheumatology Research and Education Foundation. “But it remains to be seen whether the data will hold up in parallel-group studies.”

Dr. Shenoy has disclosed no relevant financial relationships.

American College of Rheumatology (ACR) 2008 Annual Scientific Meeting: Abstract 639. Presented October 26, 2008.

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