Pharmacologic Treatment of Pulmonary Arterial Hypertension

Policy ID: I-18-030

Section: Injections

Effective Date: July 01, 2018

Revised Date: March 19, 2024

Revision Effective Date: April 01, 2024

Last Reviewed: March 19, 2024

Applies To: Commercial and Medicaid Expansion

Description

Pulmonary arterial hypertension (PAH) is a chronic, progressive condition characterized by abnormally high pulmonary vascular pressure. PAH is a rare and debilitating disease associated with abnormal proliferation of smooth muscle cells in the pulmonary arterial system, causing progressive right ventricular dilation and low cardiac output. Interstitial lung disease (ILD) is a group of lung diseases characterized by significant fibrosis (scarring) of the bronchioles and alveolar sacs within the lungs. Increased fibrotic tissue prevents oxygenation and free gas exchange causing shortness of breath with activity, labored breathing, and fatigue. Pulmonary hypertension complicates the course of individuals with ILD and may contribute to worse functional status.

Note: Epoprostenol (Flolan, Veletri) and treprostinil (Remodulin) may be covered under the medical benefit. Tadalafil (Adcirca, Alyq, Tadliq), riociguat (Adempas), ambrisentan (Letairis), macitentan (Opsumit), treprostinil (Orenitram, Tyvaso), sildenafil (Liqrev, Revatio), bosentan (Tracleer), selexipag (Uptravi) and iloprost (Ventavis) may be covered under the pharmacy benefit

Policy Application

All claims submitted for this policy will be processed according to the policy effective date and associated revision effective dates in effect on the date of service.

Criteria

Coverage is subject to the specific terms of the member's benefit plan.

Federal Employee Program members (FEP) should check with their Retail Pharmacy Program to determine if prior approval is required by calling the Retail Pharmacy Program at 1-800-624-5060 (TTY: 1-800-624-5077). FEP members can also obtain the list through the www.fepblue.org website.

A diagnosis of PAH must be confirmed by a right heart catheterization. Documentation confirming the results of the right heart catheterization diagnosing PAH must be available prior to receiving any of the advanced therapy drugs listed in this policy. Exception to this requirement may be allowed for pediatric individuals where the risk outweighs the benefit of catheterization or established Eisenmenger syndrome (with appropriate clinical and noninvasive diagnostic evaluations). If heart catheterization is not performed submission of alternative studies such as but not limited to contrast-enhanced computed tomography (CT) scan, magnetic resonance imaging (MRI) or other specified testing (e.g., for congenital metabolic diseases, gastroesophageal reflux disease).

Epoprostenol sodium (Flolan^®, Veletri^®) continuous intravenous (IV) infusion

Epoprostenol (Flolan, Veletri) sodium may be considered medically necessary when ALL of the following are met:

The individual has a diagnosis of PAH World Health Organization Group 1 (PAH [WHO Group I]) with documented WHO Functional Class (FC) III-IV symptoms; and
The prescriber has submitted the results of a right heart catheterization substantiating ALL of the following:
- Mean pulmonary artery pressure (mPAP) greater than or equal to 20 mmHg; and
- Pulmonary wedge pressure (PWP)* less than or equal to 15 mmHg; and
- Pulmonary vascular resistance (PVR) greater than or equal to three (3) Wood units.

Reauthorization Criteria

Continuation of therapy with epoprostenol (Flolan, Veletri) may be considered medically necessary when the following criteria are met:

Individual demonstrates disease stability or clinically meaningful response to therapy.

Procedure Code

J1325

Treprostinil (Remodulin) continuous subcutaneous (SQ) or IV infusion

Treprostinil (Remodulin) may be considered medically necessary when ALL of the following are met:

The individual has a diagnosis of PAH (WHO Group 1) with documented WHO-FC II-IV symptoms; or
The individual has a diagnosis of PAH (WHO Group 1) and requires transition from epoprostenol sodium (e.g., Flolan ^® , Veletri ^® ); and
The prescriber has submitted the results of a right heart catheterization substantiating ALL of the following:
- Mean pulmonary artery pressure (mPAP) greater than or equal to 20 mmHg; and
- Pulmonary wedge pressure (PWP)* less than or equal to 15 mmHg; and
- Pulmonary vascular resistance (PVR) greater than or equal to 3 Wood units.

Reauthorization Criteria

Continuation of therapy with treprostinil (Remodulin) may be considered medically necessary when the following criteria are met:

Individual demonstrates disease stability or clinically meaningful response to therapy.

Procedure Code

J3285

Combination therapy may be considered medically necessary for the treatment of PAH (WHO Group I) with documented WHO-FC II-IV symptoms when ALL of the following are met:

Individual has failed to demonstrate an adequate response to monotherapy; and
Medications are from different therapeutic classes.

Use of epoprostenol (Flolan, Veletri) is considered not medically necessary as a treatment for individuals who demonstrate a favorable acute hemodynamic response to vasodilators (vaso-responder) at cardiac catheterization who are deemed appropriate by the treating physician for a trial of calcium channel blocker treatment.

Procedure Codes

J1325

J3285

The use of epoprostenol (Flolan, Veletri) or treprostinil (Remodulin) is considered experimental/investigational and therefore non-covered due to lack of scientific based evidence for the treatment of non-PAH conditions, WHO Groups II-V, including but not limited to:

Pulmonary hypertension (PH) associated with left heart diseases; or
PH associated with lung diseases and/ or hypoxemia (including chronic obstructive pulmonary disease); or
PH due to chronic thrombotic and/or embolic disease; or
Miscellaneous group (i.e., sarcoidosis, histiocytosis X, and lymphangiomatosis).

The use of epoprostenol (Flolan, Veletri) or treprostinil (Remodulin) not meeting the criteria as indicated in this policy is considered experimental/investigational and therefore non-covered because the safety and/or effectiveness of this service cannot be established by the available published peer-reviewed literature.

Procedure Codes

J1325

J3285

NOTE: In addition to the above criteria, product specific dosage and/or frequency limits may apply in accordance with the United States Food and Drug Administration (U.S. FDA)-approved product prescribing information, national compendia, Centers for Medicare and Medicaid Services (CMS) and other peer reviewed resources or evidence-based guidelines.

Diagnosis Codes

Covered Diagnosis Codes for Procedure Codes J1325 or J3285

I27.0

I27.20

I27.21

I27.29

I27.89

Professional Statements and Societal Positions Guidelines

The World Health Organization (WHO) classifies pulmonary hypertension (PH) into five (5) categories based on the disease etiology. These diagnostic classifications include:

Group I pulmonary arterial hypertension
Group II pulmonary hypertension with left heart disease
Group III pulmonary hypertension associated with lung disease and/or hypoxemia
Group IV pulmonary hypertension due to chronic thromboembolic disease
Group V pulmonary hypertension with unclear multifactorial mechanisms.

Functional assessment of individuals with Pulmonary Arterial Hypertension (PAH) is based on the severity of the disease, which is classified according to the clinical symptoms on a scale of I to IV. Categorization is based on the WHO classification system, which has been modified for PAH from the New York Heart Association (NYHA) functional classifications of individuals with cardiac disease.

WHO Functional Classification for Pulmonary Arterial Hypertension (PAH):

Class I

No limitation of clinical activity; ordinary physical activity does not cause dyspnea or fatigue.

Class II

Slight limitation in physical activity; ordinary physical activity produces dyspnea, fatigue, chest pain, or near-syncope; no symptoms at rest.

Class III

Marked limitation of physical activity; less than ordinary physical activity produces dyspnea, fatigue, chest pain, or near-syncope; no symptoms at rest.

Class IV

Unable to perform any physical activity without symptoms; dyspnea and/or fatigue present at rest; discomfort increased by any physical activity.

New York Heart Association (NYHA) Functional Classifications:

Class I

Individuals with no limitation of activities; they suffer no symptoms from ordinary activities

Class II

Individuals with slight, mild limitation of activity; they are comfortable with rest or mild exertion.

Class III

Individuals with marked limitation of activity; they are comfortable only at rest.

Class IV

Individuals who should be at complete rest, confined to bed or chair; any physical activity brings on discomfort and symptoms occur at rest.

American College of Chest Physicians

In 2019, the American College of Chest Physicians updated guidelines on pharmacologic therapy for PAH in adults. Relevant recommendations include:

For treatment-naive PAH individuals with WHO FC III symptoms who are not candidates for, or who have failed CCB therapy, therapy is recommended to be initiated with a combination of ambrisentan and tadalafil. For individuals who are unwilling or unable to tolerate combination therapy, monotherapy with a currently approved ERA, a PDE5I, or the soluble guanylate cyclase stimulator riociguat is recommended.
For treatment naive PAH individuals with WHO FC III symptoms who have evidence of rapid progression of their disease, or other markers of a poor clinical prognosis, consider initial treatment with a parenteral prostanoid.
For PAH individuals in WHO FC III who have evidence of progression of their disease, and/or markers of poor clinical prognosis despite treatment with one or two classes of oral agents, consider the addition of a parenteral or inhaled prostanoid.
For treatment naive PAH individuals in WHO FC IV, initiation of therapy with a parenteral prostanoid agent is recommended. For treatment naive PAH individuals in WHO FC IV who are unable or do not desire to manage parenteral prostanoid therapy, treatment with an inhaled prostanoid in combination with an oral PDE5I and an ERA is recommended.

ND Committee Review

Internal Medical Policy Committee 11-19-2020 Annual review, no clinical content change

Internal Medical Policy Committee 1-19-2021 Documentation confirming the results of the right heart catheterization diagnosing PAH is now a criteria for all drug approvals. An exception may be made for pediatric individuals, and

Updated Combination therapy criteria.

Internal Medical Policy Committee 11-23-2021

Clarified medical versus pharmacy benefit drugs in policy

Internal Medical Policy Committee 3-23-2022 Updated description,

Updated criteria; and
Added reauthorization criteria; and
Removed K0455; K0730; and S0155 from the policy; and
Updated experimental/investigational statement; and
Updated professional statement and societal positions

Internal Medical Policy Committee 9-28-2022 - Effective October 01, 2022

Added Tyvaso DPI, J3535, to the policy

Internal Medical Policy Committee 9-12-2023

Annual review, no clinical content change

Internal Medical Policy Committee 3-19-2024 Effective April 01, 2024

Added Tadliq (tadalafil) and Liqrev (sildenafil) to the pharmacy benefit list; and
Removed pharmacy drug procedure codes.

Links

References (PDF)

Disclaimer

Current medical policy is to be used in determining a Member's contract benefits on the date that services are rendered. Contract language, including definitions and specific inclusions/exclusions, as well as state and federal law, must be considered in determining eligibility for coverage. Members must consult their applicable benefit plans or contact a Member Services representative for specific coverage information. Likewise, medical policy, which addresses the issue(s) in any specific case, should be considered before utilizing medical opinion in adjudication. Medical technology is constantly evolving, and the Company reserves the right to review and update medical policy periodically.

Policy ID: I-18-029

Section: Injections

Effective Date: July 01, 2018

Revised Date: August 31, 2022

Revision Effective Date: October 01, 2022

Last Reviewed: September 12, 2023

Archived Date: March 31, 2024

Applies To: Commercial and Medicaid Expansion

Description

Note: Epoprostenol (Flolan, Veletri) and treprostinil (Remodulin) may be covered under the medical benefit. Tadalafil (Adcirca, Alyq), riociguat (Adempas), ambrisentan (Letairis), macitentan (Opsumit), treprostinil (Orenitram, Tyvaso), sildenafil (Revatio), bosentan (Tracleer), selexipag (Uptravi) and iloprost (Ventavis) may be covered under the pharmacy benefit.

Criteria

Coverage is subject to the specific terms of the member's benefit plan.

Epoprostenol sodium (Flolan^®, Veletri^®) continuous intravenous (IV) infusion

Epoprostenol (Flolan, Veletri) sodium may be considered medically necessary when ALL of the following are met:

The individual has a diagnosis of PAH World Health Organization Group 1 (PAH [WHO Group I]) with documented WHO Functional Class (FC) III-IV symptoms; and
The prescriber has submitted the results of a right heart catheterization substantiating ALL of the following:
- Mean pulmonary artery pressure (mPAP) greater than or equal to 20 mmHg; and
- Pulmonary wedge pressure (PWP)* less than or equal to 15 mmHg; and
- Pulmonary vascular resistance (PVR) greater than or equal to 3 Wood units.

Reauthorization Criteria

Continuation of therapy with epoprostenol (Flolan, Veletri) may be considered medically necessary when the following criteria are met:

Individual demonstrates disease stability or clinically meaningful response to therapy.

Procedure Codes

J1325

Treprostinil (Remodulin) continuous subcutaneous (SQ) or IV infusion

Treprostinil (Remodulin) may be considered medically necessary when ALL of the following are met:

The individual has a diagnosis of PAH (WHO Group 1) with documented WHO-FC II-IV symptoms; or
The individual has a diagnosis of PAH (WHO Group 1) and requires transition from epoprostenol sodium (e.g. Flolan^®, Veletri^®); and
The prescriber has submitted the results of a right heart catheterization substantiating ALL of the following:
- Mean pulmonary artery pressure (mPAP) greater than or equal to 20 mmHg; and
- Pulmonary wedge pressure (PWP)* less than or equal to 15 mmHg; and
- Pulmonary vascular resistance (PVR) greater than or equal to 3 Wood units.

Reauthorization Criteria

Continuation of therapy with treprostinil (Remodulin) may be considered medically necessary when the following criteria are met:

Individual demonstrates disease stability or clinically meaningful response to therapy.

Procedure Codes

J3285

Tadalafil (Adcirca, Alyq), riociguat (Adempas), ambrisentan (Letairis), macitentan (Opsumit), treprostinil (Orenitram, Tyvaso), sildenafil (Revatio), bosentan (Tracleer), selexipag (Uptravi) and iloprost (Ventavis) may be covered under the pharmacy benefit.

Procedure Codes

J3490

J3535

J7686

J8499

Q4074

Combination therapy may be considered medically necessary for the treatment of PAH (WHO Group I) with documented WHO-FC II-IV symptoms when ALL of the following are met:

Individual has failed to demonstrate an adequate response to monotherapy; and
Medications are from different therapeutic classes.

Procedure Codes

J1325

J3285

J3490

J3535

J7686

J8499

Q4074

Pulmonary hypertension (PH) associated with left heart diseases; or
PH associated with lung diseases and/ or hypoxemia (including chronic obstructive pulmonary disease); or
PH due to chronic thrombotic and/or embolic disease; or
Miscellaneous group (i.e., sarcoidosis, histiocytosis X, and lymphangiomatosis).

Procedure Codes

J1325

J3285

NOTE: In addition to the above criteria, product specific dosage and/or frequency limits may apply in accordance with the U.S. Food and Drug Administration (FDA)-approved product prescribing information, national compendia, Centers for Medicare and Medicaid Services (CMS) and other peer reviewed resources or evidence-based guidelines.

Diagnosis Codes

Covered Diagnosis Codes for Procedure Codes J1325 or J3285

I27.0

I27.20

I27.21

I27.29

I27.89

Professional Statements and Societal Positions Guidelines

The World Health Organization (WHO) classifies pulmonary hypertension (PH) into five (5) categories based on the disease etiology. These diagnostic classifications include:

Group I pulmonary arterial hypertension
Group II pulmonary hypertension with left heart disease
Group III pulmonary hypertension associated with lung disease and/or hypoxemia
Group IV pulmonary hypertension due to chronic thromboembolic disease
Group V pulmonary hypertension with unclear multifactorial mechanisms.

Functional assessment of patients with Pulmonary Arterial Hypertension (PAH) is based on the severity of the disease, which is classified according to the clinical symptoms on a scale of I to IV. Categorization is based on the WHO classification system, which has been modified for PAH from the New York Heart Association (NYHA) functional classifications of patients with cardiac disease.

WHO Functional Classification for Pulmonary Arterial Hypertension (PAH):

Class I

No limitation of clinical activity; ordinary physical activity does not cause dyspnea or fatigue.

Class II

Slight limitation in physical activity; ordinary physical activity produces dyspnea, fatigue, chest pain, or near-syncope; no symptoms at rest.

Class III

Marked limitation of physical activity; less than ordinary physical activity produces dyspnea, fatigue, chest pain, or near-syncope; no symptoms at rest.

Class IV

Unable to perform any physical activity without symptoms; dyspnea and/or fatigue present at rest; discomfort increased by any physical activity.

New York Heart Association (NYHA) Functional Classifications:

Class I

Patients with no limitation of activities; they suffer no symptoms from ordinary activities

Class II

Patients with slight, mild limitation of activity; they are comfortable with rest or mild exertion.

Class III

Patients with marked limitation of activity; they are comfortable only at rest.

Class IV

Patients who should be at complete rest, confined to bed or chair; any physical activity brings on discomfort and symptoms occur at rest.

American College of Chest Physicians

In 2019, the American College of Chest Physicians updated guidelines on pharmacologic therapy for PAH in adults. Relevant recommendations include:

For treatment-naive PAH patients with WHO FC III symptoms who are not candidates for, or who have failed CCB therapy, therapy is recommended to be initiated with a combination of ambrisentan and tadalafil. For patients who are unwilling or unable to tolerate combination therapy, monotherapy with a currently approved ERA, a PDE5I, or the soluble guanylate cyclase stimulator riociguat is recommended.
For treatment naive PAH patients with WHO FC III symptoms who have evidence of rapid progression of their disease, or other markers of a poor clinical prognosis, consider initial treatment with a parenteral prostanoid.
For PAH patients in WHO FC III who have evidence of progression of their disease, and/or markers of poor clinical prognosis despite treatment with one or two classes of oral agents, consider the addition of a parenteral or inhaled prostanoid.
For treatment naive PAH patients in WHO FC IV, initiation of therapy with a parenteral prostanoid agent is recommended. For treatment naive PAH patients in WHO FC IV who are unable or do not desire to manage parenteral prostanoid therapy, treatment with an inhaled prostanoid in combination with an oral PDE5I and an ERA is recommended.

ND Committee Review

Internal Medical Policy Committee 11-19-2020 Annual review, no clinical content change

Combination therapy criteria updated.

Internal Medical Policy Committee 11-23-2021 Clarified medical versus pharmacy benefit drugs in policy

Internal Medical Policy Committee 3-23-2022 Updated description,

Updated criteria, and
Added reauthorization criteria, and
Removed K0455, K0730 and S0155 from the policy, and
Updated experimental/investigational statement, and
Updated professional statement and societal positions

Internal Medical Policy Committee 9-28-2022 - Effective October 01, 2022

Added Tyvaso DPI, J3535, to the policy

Internal Medical Policy Committee 9-12-2023

Annual review, no clinical content change

Links

References (PDF)

Disclaimer

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