Safety and Efficacy of B-Cell Depletion with Rituximab for the Treatment of Systemic Sclerosis–associated Pulmonary Arterial Hypertension: A Multicenter, Double-Blind, Randomized, Placebo-controlled Trial

Reply to Andréasson et al.: Multiple Manifestations of Systemic Sclerosis Affect Walk Distance

“…We agree with the concern raised by Andréasson and colleagues in response to the rituximab trial which tested B cell depletion as a therapy for systemic sclerosis (SSc)-associated pulmonary arterial hypertension (PAH) (1). In short, we acknowledge that systemic sclerosis is a multisystem disease and that putative improvements in the 6-minute walk distance (6MWD) can be attributable to changes in conditions not directly related to PAH.…”

Systemic Sclerosis-Associated Pulmonary Hypertension: Spectrum and Impact

“…Dual upfront combination therapy has certainly been a significant therapeutic advance in this disease and offers new hopes for SSc-PAH [68,97] which, however, remains the leading cause of morbidity and mortality. Whether specific targeting of immune pathogenic mechanisms may be the key for better outcomes remains unclear at this time [106]. It is also possible that a better understanding of fibrotic processes (a key pathologic feature in this syndrome) may lead to targeted therapy with drugs such as tyrosine kinase inhibitors which are currently being tested in clinical PAH trials.…”

“…When data through week 48 were also considered, the estimated change in 6MW distance was 25.5 ± 8.8 m for rituximab and 0.4 ± 7.4 m for placebo (p = 0.03). In addition, rituximab appeared to be safe and well tolerated [106]. Further work is needed to validate the potential benefit of this promising approach as adjuvant therapy.…”

What’s new in pulmonary hypertension clinical research: lessons from the best abstracts at the 2020 American Thoracic Society International Conference

“…which predicted a favorable therapy response 152 . An increasing number of novel PAH therapies have failed in clinical trials despite preclinical success.…”

“…ML has been increasingly utilized for a variety of PH research applications. Supervised ML approaches have already been applied to facilitate automated non-invasive PH diagnosis (from claims-based data, 146 cardiac imaging parameters, 147 , 148 and blood biomarkers 149 ) prognosticate PH outcomes (from clinical and imaging features 150 , 151 ) and predict therapy responders (from blood biomarkers 152 ) Unsupervised ML has also been utilized, identifying four PAH immune phenotypes with distinct circulating inflammatory profiles that are independent of clinical subtypes and stratify mortality risk. 153 It is important to be aware of potential pitfalls as ML applications are increasingly reported in PAH.…”