New real-world observational analysis of Uptravi underscores the importance of risk assessment for treating pulmonary arterial hypertension patients -Johnson & Johnson
Findings from an analysis of the first 500 patients enrolled in the SPHERE registry (SelexiPag: tHe usErs dRug rEgistry) found more than three-quarters (76%) of pulmonary arterial hypertension (PAH) patients treated with Uptravi (selexipag)
from Johnson & Johnson, either maintained (56%) or reduced (20%) their one-year mortality risk score.
The SPHERE results were published in the April issue of the Journal of Heart and Lung Transplantation (JHLT).
SPHERE is an ongoing real-world, observational, user registry using two different risk assessment methods that describes the clinical characteristics, outcomes and dosing/titration regimens in patients with PAH who are being treated with Uptravi.
<p In treating patients with PAH, routine comprehensive risk assessment is strongly recommended by the 2015 European Society of Cardiology and the European Respiratory Society (ESC/ERS) Guidelines, as there is no single variable that can provide sufficient diagnostic and prognostic information. Additionally, achieving and/or maintaining a low-risk profile is a recommended adequate treatment response for patients with PAH.
In the analysis of the data from the SPHERE registry risk categories for one-year mortality are assigned to patients using two different assessments, the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) and the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) risk calculators, and PAH patients are classified as low, intermediate or high risk. Results from this analysis showed that at the end of the 18-month follow-up, 19.2% of patients had a lower REVEAL 2.0 risk score, 57.8% experienced no change in their REVEAL 2.0 risk score, and 20.2% noticed an increase in their REVEAL 2.0 risk score. The findings in this analysis were consistent with the COMPERA calculations as well, as 21.4% of patients experienced a positive change in their risk category (moving from a more serious to less serious category), 54.4% maintained their risk category, and 19.4% experienced a negative change in their risk category (moving from a less serious to a more serious category.
SPHERE enrolled patients who were either newly initiated on Uptravi ( less than 60 days before enrollment) or previously received Uptravi with documentation of dose titration at study enrollment. Data from this SPHERE analysis suggest that 87.8% of patients titrated Uptravi at a slower rate than 200-mcg BID increments, revealing that in the real-world environment patients were titrated less than the recommended titration schedule in the GRIPHON study.
Data from SPHERE are limited to what is collected during routine clinical visits, and patients are observed for up to 18 months after enrollment . In this cohort, 94.8% of patients have PAH (WHO Group I), most commonly idiopathic (49.2%) followed by connective tissue disease (CTD)-associated PAH (26.4%). 31.0% and 49.6% of patients have WHO FC II and WHO FC III disease at baseline respectively. There were no new safety signals identified with Uptravi in the real-world setting, and the incidence of discontinuation due to Uptravi treatment-related adverse events (AEs) remained low in the SPHERE analysis (7.2%). The most common AEs leading to discontinuation were headache (6.5%) and diarrhea (5.1%) in newly initiated patients, and worsening PAH (3.3%) and right ventricular failure (1.9%) in previously initiated patients.
Real-World Data Limitations : Real-world data have the potential to supplement randomized controlled trial data by providing additional information as to how a medicine performs in routine clinical practice. There are limitations, however, and real-world data cannot be used as stand-alone evidence to validate the efficacy or safety of a treatment
PAH is a rapidly progressive disease with no known cure. For individuals with PAH, risk assessment is necessary to evaluate disease progression and inform treatment decisions based on patients’ prognosis. Uptravi is an oral prostacyclin pathway agent (PPA) indicated for the treatment of patients with PAH (World Health Organization [WHO] Group I, functional class [FC] II-III) to delay disease progression and reduce the risk of hospitalization. In the pivotal GRIPHON trial, Uptravi was proven to reduce the risk of disease progression by 40%.
See- VOLUME 40, ISSUE 4, P279-288, APRIL 01, 2021 PDF [676 KB] -“Patient and disease characteristics of the first 500 patients with pulmonary arterial hypertension treated with selexipag in real-world settings from SPHERE.”-
Nick H. Kim, MD ,Anna R. Hemnes, MD, Murali M. Chakinala, MD, Carol Zhao, MS ,et al. .Published:January 14, 2021DOI:https://doi.org/10.1016/j.healun.2021.01.006-Journal of Heart and Lung Transplantation.