Over time, patients with longstanding pulmonary arterial hypertension (PAH) experience pressure overload in the right ventricle (RV), leading to reduced contractile force and chamber dilation. Present strategies to treat PAH consist of pulmonary arterial vasodilators by way of the prostacyclin, endothelin, or nitric oxide pathways. It is now appreciated that maladaptive inflammatory signaling is a key contributor to the development of obliterative pulmonary arteriolar lesions and RV failure in PAH (1, 2), and that IL-1 and IL-6 levels correlate with the degree of RV failure (3). With experimental animal data suggesting anakinra (recombinant IL-1 receptor antagonist) protects against development of PAH (4), we designed a single-group, open-label phase IB/II pilot study (clinicaltrials. gov identifier: NCT03057028) to evaluate the feasibility and safety of treatment with anakinra as add-on therapy to standard of care in patients with stable PAH and RV failure. In addition to the preclinical data, anakinra was chosen on the basis of multiple favorable clinical trials in left-sided systolic dysfunction by our group (5, 6). Here we report the findings from our pilot study. From October 2017 to May 2018, patients at the Virginia Commonwealth University treated for pulmonary hypertension were screened for eligibility. Inclusion criteria included group 1 PAH (7)(not associated with connective tissue disease, human immunodeficiency virus, portal hypertension, or schistosomiasis), age. 18 years, and symptomatic RV failure (objective findings of RV dysfunction by echocardiography [RV diastolic diameter. 4.3 cm, fractional area change, 35%, or tricuspid annular plane systolic excursion< 1.5 cm] with New York Heart Association class II or III heart failure symptoms) despite optimal PAH therapy. Exclusion criteria included autoimmune/autoinflammatory diseases, anti-inflammatory medications, recent malignancy or infection, and severe renal dysfunction. Of the 39 patients who met inclusion criteria, 10 were excluded (chronic inflammatory disorders [n= 4], infection [n= 1], severe renal dysfunction [n= 2], non–English speaking [n= 1], unable to consent [n= 1], pregnant [n= 1]). Sixteen patients were approached for the study: 6 declined to participate, and 10 agreed to enroll, which was the sample size chosen to gather preliminary data. However, scheduling conflicts prevented two patients from completing baseline testing, and one patient was hospitalized for urosepsis before enrollment. Thus, seven patients were enrolled in the study, in which they provided signed consent (approved by the institutional review board) and received anakinra 100 mg subcutaneously daily for 14 days, which is the dose approved by the US Food and Drug Administration for the treatment of rheumatoid arthritis. Baseline testing before treatment included biomarkers (high-sensitivity C-reactive protein [hsCRP], IL-6, and N-terminal pro B-type natriuretic peptide [NT-proBNP]), quality-of-life questionnaires (Duke Activity Severity Index and Minnesota Living with Heart Failure Questionnaire), transthoracic echocardiography, and cardiopulmonary exercise testing for measurement of peak oxygen consumption and ventilatory efficiency (V