Reversible Pulmonary Arterial Hypertension Associated with Interferon‐Beta Treatment for Multiple Sclerosis

Abstract

Interferon (IFN) therapy has an important role in the treatment of multiple sclerosis and chronic hepatitis C infection. A few case reports have described an association between IFN therapy and the development of irreversible pulmonary arterial hypertension (PAH), and it is currently listed as a possible drug-induced cause of PAH in the most recent classification of pulmonary hypertension. A causal link between IFN use and PAH remains to be elucidated; many reports of PAH resulting from IFN occur in individuals with some other risk factor for PAH. The authors present a case involving a patient with multiple sclerosis with no known risk factors for PAH, who developed severe PAH after exposure to IFN therapy. The patient experienced significant clinical and hemodynamic improvement, with normalization of her pulmonary pressures after the initiation of combination therapy for PAH. At 28 months after diagnosis, she remains asymptomatic with no hemodynamic evidence of PAH and has been off all PAH therapy for 10 months.

Pulmonary arterial hypertension in patients treated with interferon

“…The analysis of disease evolution after IFN discontinuation provides additional support for a causal role of IFN. Spontaneous and complete reversal of PAH was seen in two cases [7,8] and in the third case, near normalisation of haemodynamics occurred after 6 months of therapy with an endothelin antagonist and phosphodiesterase-5 inhibitor.…”

Is pulmonary arterial hypertension associated with interferon-β therapy for multiple sclerosis reversible? A case study to explore the complexity

“…Τhe Sixth World Symposium on Pulmonary Hypertension, based on recent data, proposed a simplified characterisation of PAH associated with drugs and toxins into two subgroups (definite and possible) to help physicians to identify drugs requiring specific surveillance. According to this framework, and supported by case series and case reports, IFN-β is classified as a drug with possible association with PAH development [2].In the literature, there are several cases of patients with multiple sclerosis (MS) on treatment with IFN-β who were diagnosed with PAH associated with the IFN-β exposure [3][4][5][6][7][8][9]. The need to identify and present related cases has been highlighted [4,5].We report a case of a patient with MS on treatment with IFN-β who subsequently developed PAH.…”

“…In the literature, there are several cases of patients with multiple sclerosis (MS) on treatment with IFN-β who were diagnosed with PAH associated with the IFN-β exposure [3][4][5][6][7][8][9]. The need to identify and present related cases has been highlighted [4,5].…”

“…Βased on reported cases [3][4][5][6][7][8][9], IFN-β was discontinued and the patient received glatiramer acetate for 2 years. After a severe optic neuritis, she is currently treated with natalizumab.…”

“…PRELLA et al [4] reported a case with marked haemodynamic improvement near normalisation 6 months after cessation of IFN-β and introduction of a double specific PAH therapy including sildenafil and macitentan. GIBBONS et al [6] described a fully reversible case after discontinuation of IFN-β and upfront combination therapy with ambrisentan and tadalafil, with complete resolution of pulmonary haemodynamics to normal values (which was sustained even with discontinuation of PAH therapy). MCGOVERN et al However, it appears that the reversal of PAH after discontinuation of IFN-β is not always possible, while PAH can be very severe leading to death or lung transplantation.…”