Bosentan Yields Long-Term Improvement of Skin Scleroderma

VIENNA — The endothelin receptor antagonist bosentan, currently used for the treatment of pulmonary hypertension, also is showing long-term beneficial effects on digital ulceration and cutaneous fibrosis in patients with scleroderma.

Short-term improvements on digital ulcers associated with Raynaud's phenomenon in patients with systemic sclerosis have previously been reported, but a group of eight patients with ulcers that have not responded to other treatments—including intravenous iloprost—now have been treated with oral bosentan for up to 18 months with continued success, according to Juan J. Alegre-Sancho, M.D., and his colleagues in the department of rheumatology, Hospital Universitario Dr. Peset, Valencia, Spain.

Five of the patients in the study have diffuse cutaneous sclerosis, and three have a more limited form of the disease. All are women, with a mean age of 41 years and mean disease duration of 14 years.

At baseline, all patients had esophageal involvement, 63% had pulmonary fibrosis, 14% had pulmonary hypertension, 25% had cardiac involvement, and 63% had calcinosis and acro-osteolysis. Mean Rodnan skin score, which assesses skin thickening on a scale of 0 to 3 by clinical palpation at 17 body sites, was 21.

Previous treatments included calcium channel blockers, topical nitrates, losartan, aspirin, corticosteroids, and D-penicillamine. Hospitalizations for iloprost infusions had been required for four of the patients, Dr. Alegre-Sancho wrote in a poster at the meeting, which was sponsored by the European League Against Rheumatism.

Ischemic digital ulcers present at baseline have healed in all patients, and the number, frequency, and time to healing of new ulcers have diminished in 63% of patients. In three patients who have been followed for 18 months and in five patients followed for 12 months, no new ulcers have developed.

The drug was given in standard dosages and was monitored according to recommended guidelines. The usual dosage of bosentan (Tracleer) is 125 mg twice daily, and patients must be followed for elevations in liver enzymes and for pregnancy prevention.

Raynaud's phenomenon has improved in frequency and severity of episodes in all patients, and three patients have been able to stop vasodilators.

Adverse events have generally been mild and transient, occurring in the first month of therapy.

In two patients, slight elevations of liver enzymes were seen, but these resolved spontaneously without dosage adjustment.

Bosentan treatment also has led to improvements in skin fibrosis, Dr. Alegre-Sancho noted in another poster session.

In these eight patients who were given the drug for ischemic digital ulcers and in three others who were being treated for scleroderma-related pulmonary hypertension, changes in skin thickness were seen beginning in the first month of therapy and continuing up to 18 months.

The improvements are first seen on the face, neck, chest, abdomen, and back; then gradually progress distally to the upper arms, thighs, forearms, and legs; and finally extend to the hands and feet.

All patients have recovered normal pigmentation, and the appearance of hyperhidrosis and hypertrichosis on the legs and arms of approximately one-third of patients suggests a recovery of normal skin structures, according to Dr. Alegre-Sancho.

VIENNA — The endothelin receptor antagonist bosentan, currently used for the treatment of pulmonary hypertension, also is showing long-term beneficial effects on digital ulceration and cutaneous fibrosis in patients with scleroderma.

Short-term improvements on digital ulcers associated with Raynaud's phenomenon in patients with systemic sclerosis have previously been reported, but a group of eight patients with ulcers that have not responded to other treatments—including intravenous iloprost—now have been treated with oral bosentan for up to 18 months with continued success, according to Juan J. Alegre-Sancho, M.D., and his colleagues in the department of rheumatology, Hospital Universitario Dr. Peset, Valencia, Spain.

Five of the patients in the study have diffuse cutaneous sclerosis, and three have a more limited form of the disease. All are women, with a mean age of 41 years and mean disease duration of 14 years.

At baseline, all patients had esophageal involvement, 63% had pulmonary fibrosis, 14% had pulmonary hypertension, 25% had cardiac involvement, and 63% had calcinosis and acro-osteolysis. Mean Rodnan skin score, which assesses skin thickening on a scale of 0 to 3 by clinical palpation at 17 body sites, was 21.

Previous treatments included calcium channel blockers, topical nitrates, losartan, aspirin, corticosteroids, and D-penicillamine. Hospitalizations for iloprost infusions had been required for four of the patients, Dr. Alegre-Sancho wrote in a poster at the meeting, which was sponsored by the European League Against Rheumatism.

Ischemic digital ulcers present at baseline have healed in all patients, and the number, frequency, and time to healing of new ulcers have diminished in 63% of patients. In three patients who have been followed for 18 months and in five patients followed for 12 months, no new ulcers have developed.

The drug was given in standard dosages and was monitored according to recommended guidelines. The usual dosage of bosentan (Tracleer) is 125 mg twice daily, and patients must be followed for elevations in liver enzymes and for pregnancy prevention.

Raynaud's phenomenon has improved in frequency and severity of episodes in all patients, and three patients have been able to stop vasodilators.

Adverse events have generally been mild and transient, occurring in the first month of therapy.

In two patients, slight elevations of liver enzymes were seen, but these resolved spontaneously without dosage adjustment.

Bosentan treatment also has led to improvements in skin fibrosis, Dr. Alegre-Sancho noted in another poster session.

In these eight patients who were given the drug for ischemic digital ulcers and in three others who were being treated for scleroderma-related pulmonary hypertension, changes in skin thickness were seen beginning in the first month of therapy and continuing up to 18 months.

The improvements are first seen on the face, neck, chest, abdomen, and back; then gradually progress distally to the upper arms, thighs, forearms, and legs; and finally extend to the hands and feet.

All patients have recovered normal pigmentation, and the appearance of hyperhidrosis and hypertrichosis on the legs and arms of approximately one-third of patients suggests a recovery of normal skin structures, according to Dr. Alegre-Sancho.

VIENNA — The endothelin receptor antagonist bosentan, currently used for the treatment of pulmonary hypertension, also is showing long-term beneficial effects on digital ulceration and cutaneous fibrosis in patients with scleroderma.

Short-term improvements on digital ulcers associated with Raynaud's phenomenon in patients with systemic sclerosis have previously been reported, but a group of eight patients with ulcers that have not responded to other treatments—including intravenous iloprost—now have been treated with oral bosentan for up to 18 months with continued success, according to Juan J. Alegre-Sancho, M.D., and his colleagues in the department of rheumatology, Hospital Universitario Dr. Peset, Valencia, Spain.

Five of the patients in the study have diffuse cutaneous sclerosis, and three have a more limited form of the disease. All are women, with a mean age of 41 years and mean disease duration of 14 years.

At baseline, all patients had esophageal involvement, 63% had pulmonary fibrosis, 14% had pulmonary hypertension, 25% had cardiac involvement, and 63% had calcinosis and acro-osteolysis. Mean Rodnan skin score, which assesses skin thickening on a scale of 0 to 3 by clinical palpation at 17 body sites, was 21.

Previous treatments included calcium channel blockers, topical nitrates, losartan, aspirin, corticosteroids, and D-penicillamine. Hospitalizations for iloprost infusions had been required for four of the patients, Dr. Alegre-Sancho wrote in a poster at the meeting, which was sponsored by the European League Against Rheumatism.

Ischemic digital ulcers present at baseline have healed in all patients, and the number, frequency, and time to healing of new ulcers have diminished in 63% of patients. In three patients who have been followed for 18 months and in five patients followed for 12 months, no new ulcers have developed.

The drug was given in standard dosages and was monitored according to recommended guidelines. The usual dosage of bosentan (Tracleer) is 125 mg twice daily, and patients must be followed for elevations in liver enzymes and for pregnancy prevention.

Raynaud's phenomenon has improved in frequency and severity of episodes in all patients, and three patients have been able to stop vasodilators.

Adverse events have generally been mild and transient, occurring in the first month of therapy.

In two patients, slight elevations of liver enzymes were seen, but these resolved spontaneously without dosage adjustment.

Bosentan treatment also has led to improvements in skin fibrosis, Dr. Alegre-Sancho noted in another poster session.

In these eight patients who were given the drug for ischemic digital ulcers and in three others who were being treated for scleroderma-related pulmonary hypertension, changes in skin thickness were seen beginning in the first month of therapy and continuing up to 18 months.

The improvements are first seen on the face, neck, chest, abdomen, and back; then gradually progress distally to the upper arms, thighs, forearms, and legs; and finally extend to the hands and feet.

All patients have recovered normal pigmentation, and the appearance of hyperhidrosis and hypertrichosis on the legs and arms of approximately one-third of patients suggests a recovery of normal skin structures, according to Dr. Alegre-Sancho.