Pulmonary hypertension (PH) represents a group of diseases characterized by raised resting pulmonary artery pressure (≥25 mmHg).1 Although PH is an uncommon disease, patients experience a high burden of disease, often being severely limited in their ability to perform everyday tasks such as shopping and housework.2,3 With an improved understanding of the mechanisms underlying PH, significant progress has been made in improving disease management and many treatments are now available. Presentations on PH at the 103rd American Thoracic Society International Congress, held in San Diego, CA, US, on May 18–23, 2018, continued to build on the knowledge base for existing treatments, as well as showcase new data from compounds in clinical development.
Bayer presented new data on riociguat, an activator of soluble guanylate cyclase pathways indicated for two types of PH. The presentations included new safety data from the ongoing EXPERT registry, which aims to collect long-term safety data on riociguat from its use in clinical practice in patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic PH (CTEPH). As of June 15, 2017, over 1,000 patients had been recruited to the registry. Consistent with results from riociguat’s clinical development program, adverse events (AEs) of special interest were infrequent and the most common AEs observed were dizziness, dyspnea, and peripheral edema.4,5
Bayer also presented the results of two studies evaluating whether abbreviated versions of the European Respiratory Society (ERS)/European Society of Cardiology (ESC) Risk Assessment Tool can distinguish between prognostic groups in patients with PAH or CTEPH. Regular risk assessment every 3–6 months based on clinical, electrocardiographic, hemodynamic, and exercise criteria is strongly recommended in PAH to monitor risk (low, intermediate, or high) of 1-year mortality, although the extensiveness of this testing represents a patient burden.6 There are no established tools for risk assessment in CTEPH. The data presented suggested that three different abbreviated versions of the ERS/ESC Risk Assessment tool were all able to discriminate between prognostic groups in both patients with PAH and CTEPH. These results suggest it is possible to lower the burden of regular mortality risk assessments, while maintaining the assessment’s crucial prognostic value.7,8
An analysis of the MOTION study by Bayer was also presented, investigating the association between Living with PF (LPF) Questionnaire score (a measure of disease impact) and other secondary endpoints.9 Previously, the MOTION study had demonstrated improvements in LPF score with riociguat after 24 weeks. The new analysis found that changes in LPF score during the MOTION study correlated with changes in other measures of disease impact including the Work Limitations Questionnaire (WLQ-8), the Short Form Health Survey (SF-12), and the 6 Minute Walk Test (6MWT); although, not the Modified Borg Dyspnoea Scale (Borg CR 10) of perceived exertion.9
Another highlight of this year’s ATS was Bellerophon’s data on a phase II clinical trial to assess the effect of pulsed inhaled nitric oxide (iNO) on targeted vasodilation, hemodynamics, and exercise capacity in patients with PH and chronic obstructive pulmonary disease (COPD).10 Despite PH being a common comorbidity of COPD, there are currently no approved treatments for patients with PH associated with COPD. Bayer’s presentation demonstrated that iNO treatment triggered acute blood vessel volume increases in all 10 patients included in the study (p=0.03). A significant positive association was found between blood vessel dilation and ventilation (p<0.01), suggesting that improved ventilation can lead to greater levels of vasodilation. Following 4 weeks of iNO treatment, patients demonstrated reductions in pulmonary arterial pressure (-19.9%, p=0.02) and had an average 50 meters increase in their 6MWD test (p=0.04). The treatment was well tolerated throughout the study. Further trials of iNO are planned but for now, these results demonstrate the potential of iNO to become the first treatment targeting PH associated with COPD.10
In summary, data on the established PH treatment riociguat continues to grow, offering insights into both its long-term, real-world safety profile and effect on clinical measures of disease impact. Also, refinements to mortality assessments for PH may be able to reduce the burden of these crucial tests for the patient, while maintaining their accuracy. Finally, new treatments, such as iNO, promise future treatment options for types of PH currently without any indications.
1. Hoeper MM, Bogaard HJ, Condliffe R, et al. Definitions and diagnosis of pulmonary hypertension. J Am Coll Cardiol. 2013;62(25 Suppl):D42–50.
2. Delcroix M, Howard L. Pulmonary arterial hypertension: the burden of disease and impact on quality of life. Eur Respir Rev. 2015;24:621–9.
3. Moreira EM, Gall H, Leening MJ, et al. Prevalence of pulmonary hypertension in the general population: The Rotterdam Study. PLoS One. 2015;10:e0130072.
4. Humbert M, Coghlan JG, Ghofrani HA, et al. Riociguat for the treatment of pulmonary arterial hypertension associated with connective tissue disease: results from PATENT-1 and PATENT-2. Ann Rheum Dis. 2017;76:422–6.
5. Klose H, Gall H, Ghofrani H-A, et al. Riociguat for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: safety update from the EXPERT registry. Am J Respir Crit Care Med. 2018;197:A5682.
6. Galie N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. Rev Esp Cardiol (Engl Ed). 2016;69:177.
7. Farber HW, Humbert M, Hoeper M, et al. Riociguat in chronic thromboembolic pulmonary hypertension (CTEPH): evaluation of abbreviated versions of the ESC/ERS risk assessment tool in CHEST-2. Am J Respir Crit Care Med. 2018;197:A3787.
8. Humbert M, Farber HW, Ghofrani H-A, et al. Riociguat in pulmonary arterial hypertension (PAH): evaluation of abbreviated versions of the ESC/ERS risk assessment tool in PATENT-2. Am J Respir Crit Care Med. 2018;197:A2123.
9. Rahaghi FF, Melendres-Groves L, Platt DM, et al. The motion study to assess the effect of riociguat on patient-reported outcomes in PAH: correlations between the living with pulmonary hypertension questionnaire and secondary endpoints. Am J Respir Crit Care Med. 2018;197:A2110.
10. Hajian B, Shivalkar B, Leemans J, et al. Pulsed inhaled nitric oxide (NO) improves exercise tolerance in severe chronic obstructive pulmonary disease (COPD) patients with pulmonary hypertension (PH). Am J Respir Crit Care Med. 2018;197:A4229.