Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase

Screening for latent tuberculosis before starting TNF-alpha inhibitors in a population with high BCG vaccination rates

It is assumed that in candidates for TNF-alpha inhibitor (TNFi) treatment, tuberculin skin test (TST) may be unreliable, since BCG vaccination causes false positive and drugs cause false negative results, favoring the use of Quantiferon or T-spot assays. However, these tests may not be readily available in all parts of the world. We aimed to determine the reliability of TST with respect to BCG vaccination and drugs in candidates for TNFi treatment, and how isoniazid is tolerated, assuming that the use of TST would result in increased isoniazid use. We included 1031 adult patients who were prescribed a TNFi for the first time. We analysed the association of BCG and drugs with TST and Quantiferon results, the determinants of a positive TST, and evaluated the tolerability of isoniazid. BCG vaccination and male sex were associated with positive TST (OR 3.56, 95% CI 1.98-6.41 and OR 2.54, 95% CI 1.75-3.68, respectively), while prednisolone and azathioprine were associated with negative TST (OR 0.63, 95% CI 0.43-0.91 and OR 0.40, 95% CI 0.11-0.76). Isoniazid was prescribed to 684 (66.3%) patients and had to be discontinued in 12.2% of these before 9 months, most commonly due to hepatotoxicity (44%). One patient developed tuberculosis despite isoniazid use. BCG vaccination may be associated with false positive TST, despite a long time since vaccination in candidates for TNFi treatment. Prednisolone and azathioprine use were associated with negative TST. Despite the high frequency of isoniazid use associated with using TST instead of QTF, isoniazid was generally well tolerated

Screening for latent tuberculosis before starting TNF-alpha inhibitors in a population with high BCG vaccination rates

It is assumed that in candidates for TNF-alpha inhibitor (TNFi) treatment, tuberculin skin test (TST) may be unreliable, since BCG vaccination causes false positive and drugs cause false negative results, favoring the use of Quantiferon or T-spot assays. However, these tests may not be readily available in all parts of the world. We aimed to determine the reliability of TST with respect to BCG vaccination and drugs in candidates for TNFi treatment, and how isoniazid is tolerated, assuming that the use of TST would result in increased isoniazid use. We included 1031 adult patients who were prescribed a TNFi for the first time. We analysed the association of BCG and drugs with TST and Quantiferon results, the determinants of a positive TST, and evaluated the tolerability of isoniazid. BCG vaccination and male sex were associated with positive TST (OR 3.56, 95% CI 1.98-6.41 and OR 2.54, 95% CI 1.75-3.68, respectively), while prednisolone and azathioprine were associated with negative TST (OR 0.63, 95% CI 0.43-0.91 and OR 0.40, 95% CI 0.11-0.76). Isoniazid was prescribed to 684 (66.3%) patients and had to be discontinued in 12.2% of these before 9 months, most commonly due to hepatotoxicity (44%). One patient developed tuberculosis despite isoniazid use. BCG vaccination may be associated with false positive TST, despite a long time since vaccination in candidates for TNFi treatment. Prednisolone and azathioprine use were associated with negative TST. Despite the high frequency of isoniazid use associated with using TST instead of QTF, isoniazid was generally well tolerated

Riociguat treatment in patients with pulmonary arterial hypertension: Final safety data from the EXPERT registry

International audienc

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

International audienc

Riociguat treatment in patients with pulmonary arterial hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension following Phase 3 randomized trials. The EXPosurE Registry RiociguaT in patients with pulmonary hypertension (EXPERT) study was designed to monitor the long-term safety of riociguat in clinical practice. Methods: EXPERT was an international, multicenter, prospective, uncontrolled, non-interventional cohort study of patients treated with riociguat. Patients were followed for at least 1 year and up to 4 years from enrollment or until 30 days after stopping riociguat treatment. Primary safety outcomes were adverse events (AEs) and serious adverse events (SAEs) coded using Medical Dictionary for Regulatory Activities preferred terms and System Organ Classes version 21.0, collected during routine clinic visits (usually every 3-6 months) and collated via case report forms. Results: In total, 326 patients with PAH were included in the analysis. The most common AEs in these patients were dizziness (11.7%), right ventricular (RV)/cardiac failure (10.7%), edema/peripheral edema (10.7%), diarrhea (8.6%), dyspnea (8.0%), and cough (7.7%). The most common SAEs were RV/cardiac failure (10.1%), pneumonia (6.1%), dyspnea (4.0%), and syncope (3.4%). The exposure-adjusted rate of hemoptysis/pulmonary hemorrhage was 2.5 events per 100 patient-years. Conclusion: Final data from EXPERT show that in patients with PAH, the safety of riociguat in clinical practice was consistent with clinical trials, with no new safety concerns identified and a lower exposure-adjusted rate of hemoptysis/pulmonary hemorrhage than in the long-term extension of the Phase 3 trial in PAH

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase 3 randomized trials. The EXPosurE Registry RiociguaT in patients with pulmonary hypertension (EXPERT) study was designed to monitor the long-term safety of riociguat in clinical practice. Methods: EXPERT was an international, multicenter, prospective, uncontrolled, non-interventional cohort study of patients treated with riociguat. Patients were followed for at least 1 year and up to 4 years from enrollment or until 30 days after stopping riociguat treatment. Primary safety outcomes were adverse events (AEs) and serious adverse events (SAEs) coded using Medical Dictionary for Regulatory Activities preferred terms and System Organ Classes version 21.0, collected during routine clinic visits and collated via case report forms. Results: In total, 956 patients with CTEPH were included in the analysis. The most common AEs in these patients were peripheral edema/edema (11.7%), dizziness (7.5%), right ventricular (RV)/cardiac failure (7.7%), and pneumonia (5.0%). The most common SAEs were RV/cardiac failure (7.4%), pneumonia (4.1%), dyspnea (3.6%), and syncope (2.5%). Exposure-adjusted rates of hemoptysis/pulmonary hemorrhage and hypotension were low and comparable to those in the long-term extension study of riociguat (Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase-Stimulator Trial [CHEST-2]). Conclusion: Data from EXPERT show that in patients with CTEPH, the safety of riociguat in routine practice was consistent with the known safety profile of the drug, and no new safety concerns were identified

Venous thromboembolism risk and prophylaxis in hospitalised medically ill patients The ENDORSE Global Survey

Limited data are available regarding the risk for venous thromboembolism (VIE) and VIE prophylaxis use in hospitalised medically ill patients. We analysed data from the global ENDORSE survey to evaluate VTE risk and prophylaxis use in this population according to diagnosis, baseline characteristics, and country. Data on patient characteristics, VIE risk, and prophylaxis use were abstracted from hospital charts. VTE risk and prophylaxis use were evaluated according to the 2004 American College of Chest Physicians (ACCP) guidelines. Multivariable analysis was performed to identify factors associated with use of ACCP-recommended prophylaxis. Data were evaluated for 37,356 hospitalised medical patients across 32 countries. VIE risk varied according to medical diagnosis, from 31.2% of patients with gastrointestinal/hepatobiliary diseases to 100% of patients with acute heart failure, active noninfectious respiratory disease, or pulmonary infection (global rate, 41.5%). Among those at risk for VTE, ACCP-recommended prophylaxis was used in 24.4% haemorrhagic stroke patients and 40-45% of cardiopulmonary disease patients (global rate, 39.5%). Large differences in prophylaxis use were observed among countries. Markers of disease severity, including central venous catheters, mechanical ventilation, and admission to intensive care units, were strongly associated with use of ACCP-recommended prophylaxis. In conclusion, VIE risk varies according to medical diagnosis. Less than 40% of at-risk hospitalised medical patients receive ACCP-recommended prophylaxis. Prophylaxis use appears to be associated with disease severity rather than medical diagnosis. These data support the necessity to improve implementation of available guidelines for evaluating VIE risk and providing prophylaxis to hospitalised medical patients