Interferon beta-1a long-term therapy related to pulmonary arterial hypertension in multiple sclerosis patients

Abstract

We report two patients with relapsing remitting multiple sclerosis (RRMS) on interferon (IFN) beta-1a treatment for more than 7 years who developed pulmonary arterial hypertension (PAH). Patient 1 developed severe PAH requiring lung transplantation. Histology showed typical proliferative lesions including plexiform lesions consistent with PAH. Patient 2 ceased IFN beta-1a, and their symptoms stabilised. Both cases highlight IFN beta-1a treatment as a potential risk factor for PAH. PAH needs to be considered as a diagnosis in patients on long-term IFN beta-1a treatment who develop new-onset respiratory symptoms.

MxA Is a Novel Regulator of Endosome-Associated Transcriptional Signaling by Bone Morphogenetic Proteins 4 and 9 (BMP4 and BMP9)

“…Indeed, an unusual example of acquired PAH occurs in patients, mainly women, who have been administered Type I interferons (IFNs). A small subset (approximately 0.5%) of patients, mainly women, administered IFN-α or β for chronic myelogenous leukemia, multiple sclerosis or other conditions developed PAH, which could be reversed in some but not all patients by cessation of the IFN therapy [7,8,9]. …”

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.…”

“…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. SAVALE et al [3] reported the fatal outcome of two patients with severe PAH and a history of IFN-β therapy for MS. FOK et al [9] reported a case where the continuation of IFN therapy together with triple specific PAH therapy, including intravenous epoprostenol, resulted in PAH worsening and pulmonary transplantation. The histopathological findings described in this case were similar to those observed in idiopathic PAH.…”