Pulmonary arterial hypertension (PAH) and cancer share elements of pathophysiology. This provides an opportunity for the cross-development of anticancer agents that can be used in improving PAH care. The adaptation of new drugs across these disease populations warrants a structured approach. This study was a 16-week, phase Ib, single-center, open-label trial of the multikinase/angiogenesis inhibitor sorafenib. In order to assess the safety of sorafenib in PAH, patients with advanced but stable disease on parenteral prostanoids (with or without oral sildenafil) were initiated on treatment at the lowest active dosage administered to cancer patients: 200 mg daily. Patients underwent weekly clinical evaluations and monthly functional testing and dose escalations to a final dosage of 400 mg twice daily. Among 12 patients (10 of them women), sorafenib was well tolerated at 200 mg twice daily. The most common adverse events were moderate skin reactions on the hands and feet and alopecia. Our conclusion was therefore that this is a tolerable dosing regimen for testing the therapeutic activity of sorafenib in PAH patients.
BackgroundIn participants with pulmonary arterial hypertension, 24 weeks of sotatercept resulted in a significantly greater reduction from baseline in pulmonary vascular resistance than placebo. This report characterises the longer-term safety and efficacy of sotatercept in the PULSAR open-label extension. We report cumulative safety, and efficacy at months 18–24, for all participants treated with sotatercept.MethodsPULSAR was a phase 2, randomised, double-blind, placebo-controlled study followed by an open-label extension, which evaluated sotatercept on top of background pulmonary arterial hypertension therapy in adults. Participants originally randomised to placebo were re-randomised 1:1 to sotatercept 0.3 or 0.7 mg·kg−1 (placebo-crossed group); those initially randomised to sotatercept continued the same sotatercept dose (continued-sotatercept group). Safety was evaluated in all participants who received ≥1 dose of sotatercept. The primary efficacy endpoint was change from baseline to months 18–24 in pulmonary vascular resistance. Secondary endpoints included 6-min walk distance and functional class. Two prespecified analyses, placebo-crossed and delayed-start, evaluated efficacy irrespective of dose.ResultsOf 106 participants enrolled in the PULSAR study, 97 continued into the extension period. Serious treatment-emergent adverse events were reported in 32 (30.8%) participants; 10 (9.6%) reported treatment-emergent adverse events leading to study discontinuation. Three (2.9%) participants died, none considered related to study drug. The placebo-crossed group demonstrated significant improvement across primary and secondary endpoints and clinical efficacy was maintained in the continued-sotatercept group.ConclusionThese results support the longer-term safety and durability of clinical benefit of sotatercept for pulmonary arterial hypertension.
BackgroundElectronic formats of patient-reported outcome (PRO) measures are now routinely used in clinical research studies. When changing from a validated paper and pen to electronic administration it is necessary to establish their equivalence. This study reports on the value of Rasch analysis in this process.MethodsThree groups of US pulmonary hypertension (PH) patients participated. The first completed an electronic version of the CAMPHOR Activity Limitation scale (e-sample) and this was compared with two pen and paper administrated samples (pp1 and pp2). The three databases were combined and analysed for fit to the Rasch model. Equivalence was evaluated by differential item functioning (DIF) analyses.ResultsThe three datasets were matched randomly in terms of sample size (n = 147). Mean age (years) and percentage of male respondents were as follows: e-sample (51.7, 16.0 %); pp1 (50.0, 14.0 %); pp2 (55.5, 40.4 %). The combined dataset achieved fit to the Rasch model. Two items showed evidence of borderline DIF. Further analyses showed the inclusion of these items had little impact on Rasch estimates indicating the DIF identified was unimportant.ConclusionsDifferences between the performance of the electronic and pen and paper administrations of the CAMPHOR Activity Limitation scale were minor. The results were successful in showing how the Rasch model can be used to determine the equivalence of alternative formats of PRO measures.
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