When used in addition to other treatments, tadalafil is effective and well tolerated in the treatment of secondary Raynaud’s phenomenon, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in San Francisco, Calif.

In Raynaud’s phenomenon blood vessels narrow abnormally when exposed to cold. This leads on to decreased blood supply to the hands and feet. Typically, Raynaud’s phenomenon results in episodic attacks where the fingers turn white and blue—sometimes accompanied by fingertip ulcers—and burn, tingle, turn red, throb, go numb, or swell. Raynaud’s phenomenon can exist alone (primary), or as a secondary condition to other diseases, such as scleroderma and lupus. Primary Raynaud’s phenomenon affects up to 5 percent of the general population. Secondary Raynaud’s phenomenon is less common than primary, but is considered more serious because the constriction of blood vessels occurs also in the internal organs.

Researchers recently studied the effectiveness and tolerability of tadalafil (Cialis®) as an additional therapy to treat patients with secondary Raynaud’s phenomenon who had not successfully responded to treatment with vasodilators—a common treatment that relaxes the smooth muscles in blood vessels.

Twenty-five patients—the majority of whom were females with an average age of 37—were randomly selected to receive either tadalafil (20 mg every-other-day) or placebo for six weeks as an add-on treatment to their usual vasodilator therapy. After the initial six weeks, patients were given a seven-day break from the tadalafil and placebo and then switched treatment: those initially receiving tadalafil began taking placebo and vice versa. Researchers recorded the frequency and duration of Raynaud’s episodes. In addition, they watched for the healing of existing, and the appearance of new fingertip ulcers, and performed physician and patient assessments of the overall severity of Raynaud’s phenomenon.

Twenty-four of the 25 patients who began the study completed it. Researchers found that, when taking tadalafil, the average daily frequency and duration of Raynaud’s episodes experienced by patients were less: 2.23 episodes versus 3.36, and 31.5 minutes versus 53.9 minutes respectively. All the 24 ulcers present at the start of treatment healed while on tadalfil, compared to only three out of 13 while on placebo. One new fingertip ulcer was reported while taking tadalafil; 13 new ulcers were reported while on placebo.

In addition, patients’ overall assessments, as well as physicians’ overall assessments of Raynaud’s phenomenon, significantly improved while patients were taking tadalafil, and no serious side effects were reported.

“This research has proven the excellent efficacy of tadalafil in the treatment of the Raynaud’s phenomenon and ischemic ulcers secondary to it,” explains Padmanabha Shenoy, MBBS, MD; senior resident; SGPGIMS, department of immunology, Lucknow, India, and lead investigator in the study. “This study also generates a new hope in the treatment of scleroderma, which is currently incurable. It has to be seen in further studies whether tadalafil can improve survival in scleroderma patients.”

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

The ACR is an organization of and for physicians, health professionals, and scientists that advances rheumatology through programs of education, research, advocacy and practice support that foster excellence in the care of people with or at risk for arthritis and rheumatic and musculoskeletal diseases. For more information on the ACR’s annual meeting, see http://www.rheumatology.org/annual.

Editor’s Notes: Dr. Shenoy will present this research during the ACR Annual Scientific Meeting at the Moscone Center from 12:15 – 12:30 PM on Sunday, October 26, in Hall C. Dr. Shenoy will be available for media questions and briefing at 1:30 PM on Monday, October 27 in the on-site press conference room, 114.

Presentation Number: 639

Efficacy of Tadalafil in Secondary Raynaud’s Phenomenon Resistant to Vasodilator Therapy: A Double Blind Randomized Cross Over Trial

Padmanabha Shenoy, Vikas Agarwal, Sudeep Kumar, Sunil Kumar Choudhary, Lalan Kumar Jha, Uttam Singh, Ramnath misra. Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India

Objective: To evaluate the efficacy and tolerability of Tadalafil as add on therapy in secondary Raynaud’s phenomenon (RP) resistant to vasodilators.

Methods: Study was conducted at a tertiary care hospital in northern India during the winter of 2007-08. Patients of scleroderma and Mixed connective tissue disease with RP resistant to vasodilators having >5 episodes/week were included in the study. Patients were randomized to receive either placebo or tadalafil (20 mg) on alternate days as add-on therapy to their current vasodilators for six weeks. After a wash out period of seven days, patients were crossed over to the other arm for another six weeks. Primary end points were improvement in the frequency and duration of Raynaud’s episodes, and Raynaud’s clinical score (RCS) recorded on a daily basis. Secondary outcome measures were healing of existing and appearance of new finger tip ulcers, physician and patient global assessment of severity of RP and improvement in scleroderma health assessment questionnaire (SSc HAQ).

Results: Twenty four of 25 recruited patients completed the study. There were 20 females. The mean age was 36.71 ± 8.43 years and mean disease duration was 6.7 ± 4.3 years. All the patients were receiving calcium channel blockers and 18 in addition were receiving other vasodilators (angiotensin receptor blockers, n=11 and angiotensin converting enzyme inhibitors, n=6). During tadalafil therapy significant improvement in mean daily frequency of RP (2.23 ± 1.43 versus 3.36 ± 1.87, P<0.001), mean daily duration of RP (31.5 ± 38.6 minute versus 53.9 ± 55.5 minute, P=0.015) and mean daily RCS (3.7 ± 2.2 versus 5.1 ± 2.5, P<0.001) were observed. All the 24 finger tip ulcers healed during tadalafil treatment as compared to three out of 13 finger tip ulcers during the placebo treatment (p<0.0001). One new finger tip ulcer was reported during tadalafil therapy as compared to 13 during placebo therapy (p=0.0005). Patient global assessment (p<0.001), physician global assessment (p<0.001) and impact of RP and finger tip ulcers on activities of daily living assessed by SSc HAQ (P<0.001) improved significantly. One patient withdrew from study due to persistent erection with the first dose of tadalafil. No serious adverse event was observed during the study.

Conclusion: Tadalafil as add on therapy is effective and well tolerated in the treatment of resistant secondary RP.

Trial registration ClinicalTrials.gov number NCT00626665.

Disclosure Block: P. Shenoy, None; V. Agarwal, None; S. Kumar, None; S.K. Choudhary, None; L.K. Jha, None; U. Singh, None; R. misra, None.

Source: American College of Rheumatology (ACR)