Treatment Guidelines

Guidelines and Experts Recommend Upfront ERA + PDE5i Therapy1,2

For treatment of patients with idiopathic, heritable, or CTD-associated PAH, based on risk assessment or other health conditions

2022 ESC/ERS guideline

2022 ESC/ERS

EVIDENCE-BASED Guideline for Upfront Therapy1

  • Low or intermediate risk

    Dual Therapy

    ERA +
    PDE5i

    (Class I)

  • High risk

    Triple
    Therapy

    ERA + PDE5i + IV/SC PPA
    (Class IIa)

  • Cardiopulmonary comorbidities

    Monotherapy

    ERA or PDE5i (Class IIa)

2024 7TH WSPH guideline

2024 7TH WSPH

Expert Consensus Opinion for Upfront Therapy2

  • Not high risk

    Dual Therapy

    ERA + PDE5i

  • High risk

    Triple
    Therapy

    ERA + PDE5i +
    IV/SC PPA

Analysis of trends in upfront dual therapy utilization3,4

Claims data icon

CLAIMS DATA

PROPORTION OF PATIENTS WITH PAH RECEIVING ERA + PDE5i THERAPY WITHIN 90 DAYS OF TREATMENT INITIATION

OCT 2021
to SEP 2022

23%

OF
PATIENTS
OCT 2022
to SEP 2024

28%

OF
PATIENTS

<1/3

Less than one-third of patients are receiving upfront dual therapy

Methodology

  • Using the regimen table, patients were selected for the cohort with a first-line treatment on or after October 1, 2021 for PAH
  • Treatment was flagged using a grouping based on ERA/PDE5i/Other
  • Using a 90-day look-forward window (from first-line start date), additional lines of therapy were considered for patients
  • If a patient is ever receiving a dual-/triple-/quadruple-combination therapy (defined by regimen table) containing ERA + PDE5i on first-line or within 90 days, they are considered dual-combination therapy with an ERA + a PDE5i

Limitations

  • Claims data analyses are limited to claims processed for insurance purposes therefore uninsured patients are not captured
  • Although the database (Supercharge) captures a large portion of lives in the US (~300 million), not all payers are captured
  • Administrative claims data are subject to potential coding errors and inconsistencies
  • Presence of a claim for a dispensed prescription does not indicate that the medication was taken as prescribed
  • Information such as some clinical parameters (eg, hemodynamics) and laboratory results and disease-specific parameters such as risk score are not available in claims data
  • Identification of PAH patients in our analysis relied upon ICD-10-CM diagnostic codes for PH and a prescription for a PAH medication
  • PDE5is may also be used for erectile dysfunction (ED) and therefore steps were taken to eliminate these patients. However, these methods cannot eliminate all non-PAH patients who receive PDE5is

Data source

Komodo/SHS US Patient Claims from October 2021-September 2024.

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ESC/ERS Guidelines
  • Clinical guidelines provide evidence-based management strategies to optimize patient care1
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WSPH2
  • Expert consensus is opinion-based guidance and may not consider all available evidence5
ESC/ERS Guidelines evaluate and specify the class and level of evidence when it comes to recommendations1
Classes of recommendations
DefinitionWording to use
CLASS I: Evidence and/or general agreement that a given treatment or procedure is beneficial, useful, and effective.Is recommended or is indicated
CLASS II: Conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of the given treatment or procedure.
  CLASS IIa: Weight of evidence/
opinion is in favor of usefulness/
efficacy.
Should be considered
  CLASS IIb: Usefulness/
efficacy is less well established by evidence/
opinion.
May be considered
CLASS III: Evidence or general agreement that the given treatment or procedure is not useful/
effective, and in some cases may be harmful.
Is not recommended
Levels of evidence
Level of evidence AData derived from multiple randomized clinical trials or meta-analyses.
Level of evidence BData derived from a single randomized clinical trial or large nonrandomized studies.
Level of evidence CConsensus of opinion of the experts and/or small studies, retrospective studies, and registries.

Compare OPSYNVI® (macitentan/ tadalafil) dosing regimen


to loose-dose combination therapy

CTD=connective tissue disease; ERA=endothelin receptor antagonist; ERS=European Respiratory Society; ESC=European Society of Cardiology; IV=intravenous; PAH=pulmonary arterial hypertension; PDE5i=phosphodiesterase type 5 inhibitor; PH=pulmonary hypertension; PPA=prostacyclin pathway agent; SC=subcutaneous; WSPH=World Symposium on Pulmonary Hypertension.

References: 1. Humbert M, Kovacs G, Hoeper MM, et al; ESC/ERS Scientific Document Group. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: the Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS). Eur Heart J. 2022;43(38):3618-3731. 2. Chin KM, Gaine SP, Gerges C, et al. Treatment algorithm for pulmonary arterial hypertension. Eur Respir J. 2024;64(4):2401325. 3. Data on file. Johnson & Johnson and its affiliates US, Inc. Komodo/SHS US patient claims from October 2021-September 2024. May 22, 2025. 4. Data on file. Johnson & Johnson and its affiliates US, Inc. Symphony plus Komodo US patient claims from October 2021-September 2024. May 22, 2025. 5. Djulbegovic B, Guyatt G. Evidence vs consensus in clinical practice guidelines. JAMA. 2019;322(8):725-726.