Safety and Efficacy of Immunoadsorption as an Add-On to Medical Treatment in Patients with Severe Idiopathic Pulmonary Arterial Hypertension

Abstract

Background: Despite optimized medical therapy, severe idiopathic pulmonary arterial hypertension (IPAH) is a devastating disease with a poor outcome. Autoantibodies have been detected in IPAH that can contribute to worsening of the disease. Objectives: The objective of this prospective, open-label, single-arm, multicenter trial was to evaluate the safety and efficacy of immunoadsorption (IA) as an add-on to optimized medical treatment for patients with IPAH. Methods: A total of 10 IPAH patients received IA over 5 days. Their clinical parameters, including hemodynamics measured by right heart catheter, were assessed at baseline and after 3 and 6 months. The primary endpoint was the change in pulmonary vascular resistance (PVR). Secondary endpoints included the change in 6-min walking distance, quality of life, safety, and plasma levels of IgG and autoantibodies. Results: The evaluation of the 10 IPAH patients (75% female; 51 ± 12 years; 166 ± 10 cm; WHO functional class III; 53% on combination therapy) revealed that IA was a safe procedure that efficiently removed IgG and autoantibodies from the circulation. After 3 months, the mean PVR improved significantly by 13.2% (p = 0.03) and the cardiac index improved by 13.1%, but no significant changes were found in 6-min walking distance. The quality of life physical functioning subscale score significantly improved after 6 months. The serious adverse events in 3 patients were possibly related to IA and included pneumonia, temporary disturbance in attention, and thrombocytopenia. Conclusions: IA as an add-on to targeted medical treatment for IPAH is a safe procedure with beneficial effects on hemodynamics, especially in patients with high levels of autoantibodies. Larger-scale controlled studies are needed to assess its efficacy in IPAH and to identify responders.

Severe but reversible pulmonary hypertension in scleromyxedema and multiple myeloma: a case report

“…Immunoadsorption (IA), another extracorporeal automated technique to selectively remove immunoglobulins from the plasma of PAH patients via high affinity absorbers, is a promising treatment for iPAH; in 5 patients with severe iPAH awaiting transplant, IA improved symptoms associated with iPAH [94]. IA as an add-on to targeted medical therapy also led to improvements in mean PVR and CI in 10 patients with iPAH though these hemodynamic improvements did not correlate to substantial improvements in the 6 mn walk test [95].…”

B-cells in pulmonary arterial hypertension: friend, foe or bystander?

“…The rationale for an effect of immunoadsorption in PAH relies on the removal of pathogenic Igs, notably anti-ETAR and anti-α1-adrenergic receptor antibodies [ 91 ]. Its efficacy is suggested by two small studies which report modest improvements in haemodynamics, right ventricle function, exercise capacity and patient-reported outcomes [ 91 , 92 ].…”

Evolving nonvasodilator treatment options for pulmonary arterial hypertension

“…A recent phase 1 trial evaluated 5 days of immunoadsorption as an add-on therapy in patients with severe idiopathic PAH to remove circulating autoantibodies that may play a role in the pathogenesis of disease. The 10 patients enrolled in the study tolerated the therapy with an acceptable safety profile and were noted to have reduced pulmonary vascular resistance at 6 months [69]. Oscillatory whole-body vibration therapy was recently evaluated in the GALILEO-PH study which randomized 22 patients with PAH to vibration therapy versus control; the patients who underwent active intervention with this novel exercise modality had improved six-minute walk distance after 4 weeks of therapy [70].…”