Treatment with Opsumit (macitentan) and Esbriet (pirfenidone) provided stable improvements in a scleroderma patient with interstitial pneumonia and borderline pulmonary arterial hypertension (PAH), according to a Japanese case report.
The study, “Systemic scleroderma-related interstitial pneumonia associated with borderline pulmonary arterial hypertension,” was published in the journal BMJ Case Reports.
Interstitial pneumonia — a disease characterized by inflammation in the walls of the lung’s tiny air sacs, or alveoli — and PAH are major causes of complications and death in patients with scleroderma. However, the appearance of new treatments, such as Actelion‘s Opsumit, have led to a significant improvement in survival.
The study presents the case of a 65-year-old woman with a 35-year history of limited skin scleroderma, who developed progressive, exercise-induced dyspnea, or shortness of breath, three months before hospital admission.
Physical examination revealed scleroderma in the arms and legs, with puffy fingers, Raynaud’s phenomenon — characterized by the narrowing of small arteries, reducing blood flow — and ankyloglossia, or tongue-tie. Fine crackles in both lungs were detected by stethoscope.
Biochemical assessments found high levels of the lung proteins, Krebs von den Lungen-6 and surfactant protein D; brain natriuretic peptides (BNP), a heart failure indicator; and antinuclear antibodies and antiribonucleoprotein antibodies, indicators of autoimmune disease.
The patient also had restrictive impairment of pulmonary function. A high-resolution computed tomography (CT) scan of the chest revealed signs possibly associated with interstitial disease in both middle and lower lobes. Left lung biopsy showed non-specific interstitial pneumonia (NSIP).
She also showed widespread fibrosis, or scarring, and enlargement of fibrotic lesions in small pulmonary arteries, resulting in significant narrowing. This led to a diagnosis of fibrocellular (involving fibers and cells) NSIP associated with scleroderma.
Initial treatment with methylprednisolone improved chest CT images. However, the patient’s symptoms and pulmonary function gradually deteriorated even with a combined therapy of prednisolone and intravenous cyclophosphamide (500 mg/m2 dose).
The patient was then found to have increased levels of BNP and borderline PAH.
Treatment with Opsumit and Genentech‘s Esbriet, with prednisolone, was started. The patient showed gradual improvements after six months, with reduced mean pulmonary artery pressure (mPAP), improved lung oxygenation, as well as decreased BNP levels. Improvements in her lung function, exercise capacity, and chest CT scan were also observed.
Maintenance of this combo treatment for 12 months helped achieve a stable clinical condition with no serious adverse effects.
“In conclusion, long-term (12-month) combination therapy of pirfenidone and macitentan can provide a clinical and radiological improvement for patients with SSc–IP [systemic sclerosis-related interstitial pneumonia] and borderline PAH when conventional treatments, such as prednisolone and/or cyclophosphamide, are ineffective,” the researchers wrote.