Erectile Dysfunction Drug Could Improve Raynaud’s Symptoms Associated with Scleroderma

Newswise — Adding tadalafil (Cialis®; Adcirca®) to the treatment of people with scleroderma can improve Raynaud’s phenomenon symptoms and heal and prevent hand and finger ulcers associated with it, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Atlanta. Scleroderma (more formally called systemic sclerosis) is a rheumatic disease that results in the thickening and tightening of skin, as well as a build-up of scar tissue and damage to internal organs. Scleroderma is a relatively uncommon problem, affecting only 200 to 300 people per million in the U.S. Some 12 to 20 new cases per million are diagnosed annually. Effective treatments are available for some forms of the disease, although scleroderma is not yet curable. The majority of patients with scleroderma also suffer from Raynaud's phenomenon – structural damage of the blood vessels that cause them to react abnormally to the cold. Raynaud’s phenomenon is commonly marked by discoloration of the hands, fingers and toes. This occurs due to poor blood flow and, in severe cases, can lead to damage such as finger ulcers, gangrene and scarring. These problems may adversely affect the functioning of the hands and quality of life during winter months.

Researchers recently completed a study to evaluate the effectiveness of adding tadalafil, a drug that can increase arterial blood flow and is commonly used to treat erectile dysfunction, to treat Raynaud's phenomenon in people with scleroderma. They studied 53 patients—of which 50 were women—whose average age was almost 37 years and who had suffered from scleroderma, on average, for almost six years. Twenty-six of the participants had limited scleroderma (which only occurs in the forearms, hands, legs, feet and face) and 27 had diffuse scleroderma (which can affect almost any area of the body). All participants met the American College of Rheumatology’s criteria for scleroderma diagnosis and had at least four Raynaud’s attacks per week.

The participants were monitored for one week to determine the initial severity of their disease and then were placed into two groups. The first group, of 26 participants, received placebo to take every-other-day in addition to their usual vasodilators (medication used to relax and widen blood vessels). The second group, of 27 participants, was given 20mg of tadalafil to take every-other-day in addition to their existing vasodilators. Participants in both groups did not know what treatment they were receiving and followed their treatment assignment for eight weeks.

Researchers then monitored the progress of each participant. They noted the number of daily Raynaud’s attacks and other measures of Raynaud’s, including the length of each individual attack, healing of existing hand and finger ulcers, appearance of new finger ulcers and improvement in scleroderma symptoms based on health and quality of life assessment questionnaires.

Researchers noticed that improvement in the tadalafil group was significantly better than in the placebo group. At the beginning of the study, 18 patients in the tadalafil group had ulcers as compared to 13 patients in the placebo group. Following treatment with tadalafil, 14 out of 18 of those patients healed completely as compared to five out of 13 patients in the placebo group. Further results revealed that new ulcers appeared in only one patient in the tadalafil group as compared to nine patients in the placebo group. Additionally, other symptoms such as dyspnea (difficulty breathing), Raynaud’s phenomenon and digital ulcers were greatly improved in those taking tadalafil. Finally, researchers noted that side effects were similar in both groups and no serious side effects were observed.

These results led researchers to believe that adding tadalafil to existing Raynaud's phenomenon therapy may be of great benefit to people with scleroderma.

“Tadalafil, in combination with other vasodilators, not only improves the number, duration and severity of Raynaud’s attacks, but also heals the existing digital ulcers as compared to placebo,” explains Vikas Agarwal, MD; associate professor of clinical immunology at the Sanjay Gandhi Postgraduate Institute of Medical Sciences and lead investigator in the study. “In addition to preventing the development of new digital ulcers, tadalafil in combination with other vasodilators marks the beginning of new phase of oral therapeutic options available for severe scleroderma.”

Patients should talk to their rheumatologists to determine their best course of treatment.

The American College of Rheumatology is an international professional medical society that represents more than 8,000 rheumatologists and rheumatology health professionals around the world. Its mission is to advance rheumatology. The ACR/ARHP Annual Scientific Meeting is the premier meeting in rheumatology. For more information about the meeting, visit www.rheumatology.org/education. Follow the meeting on twitter by using the official hashtag: #ACR2010.

Editor’s Notes: Vikas Agarwal, MD will present this research during the ACR Annual Scientific Meeting at the Georgia World Congress Center at 11:45 AM on Wednesday, November 10 in the Hall A3. Dr. Agarwal will be available for media question and briefing at 1:30 PM on Tuesday, November 9 in the on-site press conference room, B212.

Learn more about living well with rheumatic disease as well as rheumatologists and the role they play in health care.

Presentation Number: 2086

Efficacy of Tadalafil in Raynaud's phenomenon secondary to systemic sclerosis: A double blind randomized placebo controlled parallel group multicentric study

Vikas Agarwal, MD, DM (Sanjay Gandhi Postgraduate Institute of Medical Sciences, India)Parasar Ghosh, MD, DM (The Institute of Post Graduate Medical Education & Research, India)Aman Sharma, MD (Post Graduate Institute of Medical Education and Research, India)Darshan Singh Bhakuni, MD (R&R Hospital, India)Sudeep Kumar, MD, DM (Sanjay Gandhi Postgraduate Institute of Medical Sciences, India) Upendra Narayan Singh, MD (Sanjay Gandhi Postgraduate Institute of Medical Sciences, India) Rajesh Vijayvergiya, MD, DM (Post Graduate Institute of Medical Education and Research, India)Mukesh Kumar Yadav, MD (Post Graduate Institute of Medical Education and Research, India)Geetabali Devi Laishram, MD (The Institute of Post Graduate Medical Education & Research, India) Alakendu Ghosh, MD (The Institute of Post Graduate Medical Education & Research, India) Bhuban Majhi, MD (The Institute of Post Graduate Medical Education & Research, India) Dipankar Mukherjee (The Institute of Post Graduate Medical Education & Research, India, Kolkata) S S Islam (The Institute of Post Graduate Medical Education & Research, India) Aditya Kapoor (Sanjay Gandhi Postgraduate Institute of Medical Sciences, India)

Body: Objective: To evaluate the efficacy of Tadalafil in Raynaud's phenomenon (RP) secondary to systemic sclerosis (SSc).

Methods: Patients with scleroderma (as per ACR criteria) having 4 Raynaud's attacks/week were randomized to receive either placebo or Tadalafil (20 mg) on alternate days as add-on-therapy to their current vasodilators for eight weeks. Primary end points were improvement in RP parameters (daily frequency, duration and Raynaud's condition score [RCS]) and healing of existing digital ulcers (DU). Secondary outcome measures were appearance of new DU and improvement in scleroderma specific health assessment questionnaire (SHAQ) and quality of life (QoL) indices.

Results: We conducted a multicenter, randomized, placebo-controlled study with a 1-week run-in period to determine baseline severity, followed by a 8-week double-blind treatment phase. Fifty three patients (26 limited, 27 diffuse SSc, 50 females) with mean age 36.8 years and mean disease duration 62.8 months were recruited in the study. All the patients were receiving vasodilators (Calcium channel blockers n=38, angiotensin receptor blockers n=16, angiotensin converting enzyme inhibitors n=8 and a combination of two vasodilators n=13. Twenty six patients were randomized to placebo and 27 to Tadalafil arm. Baseline frequency, duration and severity of RP were not different between the two groups. Improvement in mean daily frequency, mean daily duration of RP and mean daily RCS was significant in the Tadalafil group (p<0.001, <0.001, <0.05, respectively), placebo (p=0.77, 0.821, 0.209, respectively) as compared to the baseline RP parameters. The mean change in daily frequency (p=0.01), duration (p=0.063) and severity (p=0.039) of RP was significantly better in the Tadalafil group as compared to placebo group. Eighteen patients in the Tadalafil group had DU as compared to 13 patients in the placebo group at baseline. Following treatment, DU healed completely in 14/18 patients in the Tadalafil group as compared to 5/13 patients in the placebo group (p=0.026). New DU appeared in one patient in the Tadalafil group as compared to 9 patients in the placebo group (p=0.004). Questions related to dyspnea (Q2), Raynaud's phenomenon (Q4) and digital ulcers (Q5) of SHAQ improved significantly in the Tadalafil group. Adverse events (AE) were similar between the two groups. No serious AE was observed.

Conclusion: Tadalafil as add-on therapy improves symptoms of RP, heals the existing DU and prevent new DU in patients with scleroderma.Clinicaltrials.gov identifier: NCT01117298

Disclosure: Vikas Agarwal, nothing to disclose; Parasar Ghosh, nothing to disclose; Aman Sharma, nothing to disclose, Darshan Bhakuni, nothing to disclose; Sudeep Kumar, nothing to disclose; Upendra Sing, nothing to disclose; Rajesh Vijayvergiya, nothing to disclose; Mukesh Yadav, nothing to disclose; Geetabali Laishram, nothing to disclose; Alakendu Ghosh, nothing to disclose; Bhuban Majhi, nothing to disclose; Dipankar Mukherjee, nothing to disclose; S Islam, nothing to disclose; Aditya kapoor, nothing to disclose.