Interstitial Lung Disease

POLICY NUMBER

L.5.01.493

Actemra (tocilizumab)

Esbriet (pirfenidone)

Ofev (nintedanib)

Tofidence (tocilizumab-bavi)

Tyenne (tocilizumab-aazg)

Please perform a formulary drug search on your patient’s member ID to ensure the prescription drug is covered under their benefit plan. The medication(s) in this medical policy may not be covered under a specific member’s benefit plan.

DESCRIPTION

Interstitial lung disease (ILD) is a large group of disorders with similar clinical, radiographic, physiologic, or pathologic manifestations. Most of these disorders are associated with pathologic abnormality in the interstitium and extensive alteration of alveolar and airway architecture and may present as progressive dyspnea, a persistent nonproductive cough, or other pulmonary symptoms. The initial evaluation of individuals with ILD is aimed at identifying the etiology of the ILD and its severity. ILDs include disorders known to be related to other diseases or exposures (rheumatic disease, environmental or drug-related) as well as unknown causes. The treatment choices and prognosis vary among the different causes and types of ILD. Disease progression is often expected despite optimal medical management.

One of the most common types of ILD is idiopathic pulmonary fibrosis (IPF). IPF is a chronic, fibrosing interstitial pneumonia that occurs spontaneously and is associated with characteristic usual interstitial pneumonia (UIP) pattern on high-resolution computed tomography (HRCT) and lung histology. A diagnosis of IPF requires exclusion of other known causes of ILD. IPF is characterized by progressive worsening of dyspnea and lung function.

Patients with other types of chronic fibrosis ILD may develop a progressive phenotype. This includes idiopathic nonspecific interstitial pneumonia, autoimmune ILDs, chronic sarcoidosis, chronic hypersensitivity pneumonitis, and exposure-related diseases such as asbestosis or silicosis. Progressive pulmonary fibrosis is defined as ILD of known or unknown etiology other than IPF with radiological evidence of pulmonary fibrosis and two of the following: worsening respiratory symptoms, physiological evidence of disease progression, and radiological evidence of disease progression. 

ILD is a common complication of many autoimmune diseases and is particularly common in patients with systemic sclerosis (SSc). Systemic sclerosis is characterized by diffuse fibrosis and vascular abnormalities affecting the skin and can manifest in pulmonary, gastrointestinal, cardiac, and renal impairment. ILD is the leading cause of death related to SSc. SSc-ILD is characterized by a nonspecific interstitial pneumonia (NSIP) with varying degrees of pulmonary inflammation and fibrosis.

Pirfenidone (Esbriet) is a pyridone indicated for the treatment of idiopathic pulmonary fibrosis.

Nintedanib (Ofev) is a tyrosine kinase inhibitor indicated for the treatment of adults with idiopathic pulmonary fibrosis, treatment of adults with chronic fibrosing ILD with a progressive phenotype, and to slow the rate of decline in pulmonary function in adult patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD).

Tocilizumab is indicated for slowing the rate of decline in pulmonary function in adult patients with SSc-ILD, and for the treatment of rheumatoid arthritis, giant cell arteritis, polyarticular juvenile idiopathic arthritis, systemic juvenile idiopathic arthritis, cytokine release syndrome, and COVID-19.

Related medical policies -

• Anti-Rheumatic Biologicals

• Giant Cell Arteritis

• Treatment of Coronavirus Disease 2019 (COVID-19)

POLICY

Prior authorization is required.

The use of samples by an individual will not be considered current or stable therapy to satisfy Medical Policy requirements.  

The following medications are not covered on any BCBSMS Formulary:

• Actemra (tocilizumab)

• Tofidence (tocilizumab-bavi)

Initial Evaluation

Esbriet (pirfenidone), Ofev (nintedanib), or Tyenne (tocilizumab-aazg) may be considered medically necessary when ALL of the following criteria are met:

1. The individual is >18 years of age;

2. The prescriber is or has consulted with a specialist in the area of the individual’s diagnosis (e.g., pathologist, pulmonologist, radiologist, rheumatologist);

3. ONE of the following:

   1. The individual has a diagnosis of idiopathic pulmonary fibrosis (IPF) and ALL of the following:

      1. The request is for Esbriet (pirfenidone) or Ofev (nintedanib);

      2. The individual has not had a significant environmental exposure known to cause pulmonary fibrosis (e.g. drugs, asbestos, beryllium, radiation, raising birds/livestock, and metal dusts);

      3. Other known causes of interstitial lung disease have been excluded (e.g. domestic and occupational environmental exposures, connective tissue diseases, drug toxicities, alternative diagnoses, etc);

      4. The individual does not have clinical evidence of active infection (e.g. bronchitis/bronchiolitis, pneumonia, and sinusitis);

      5. ONE of the following:

         1. A high-resolution computed tomography (HRCT) scan shows a pattern for usual interstitial pneumonia (UIP);

         2. A surgical lung biopsy with pathology confirms UIP; OR

         3. A HRCT scan shows a pattern for probable UIP AND a surgical lung biopsy with pathology indicates probable UIP;

      6. The individual’s predicted FVC ≥50%;

      7. The individual’s carbon monoxide diffusion capacity (%DLco) is between 30% to 79% predicted; AND

      8. The individual does NOT demonstrate relevant airway obstruction (i.e. FEV1/FVC <0.7);

   2. The individual has a diagnosis of systemic sclerosis-associated interstitial lung disease and BOTH of the following:

      1. The individual’s diagnosis has been confirmed on HRCT; AND

      2. ONE of the following:

         1. The request is for Tyenne and ALL of the following:

            1. The individual is not currently being treated with another immunomodulatory agents (i.e., TNF-inhibitor, IL-inhibitor, JAK inhibitor, Otezla, etc.); AND

            2. ONE of the following:

               • The individual has tried and had an inadequate response to ONE conventional agent (i.e. mycophenolate mofetil, cyclophosphamide, azathioprine); OR

               • The individual has an intolerance, hypersensitivity, or FDA-labeled contraindication to ALL conventional agents; OR

         2. The request agent is Ofev and ALL of the following:

            1. The individual’s predicted FVC ≥40%;

            2. The individual’s carbon monoxide diffusion capacity (%DLco) is between 30% to 89% predicted;

            3. The individual does NOT demonstrate relevant airway obstruction (i.e. FEV1/FVC <0.7); AND

            4. ONE of the following:

               • The individual has tried and had an inadequate response to ONE conventional agent (i.e. mycophenolate mofetil, cyclophosphamide, azathioprine) AND to tocilizumab; OR

               • The individual has an intolerance, hypersensitivity, or FDA-labeled contraindication to tocilizumab and ALL conventional agents; OR

   3. The individual has a diagnosis of chronic fibrosing interstitial lung disease (ILD) with a progressive phenotype and ALL of the following:

      1. The requested agent is Ofev;

      2. The individual has greater than 10% fibrotic features on HRCT;

      3. The individual presented with clinical signs of progression defined by ONE of the following:

         1. FVC decline greater than or equal to 10%;

         2. FVC decline greater than or equal to 5% and less than 10% with worsening respiratory symptoms or increasing extent of fibrotic changes on chest imaging; OR

         3. Worsening respiratory symptoms and increasing extent of fibrotic changes on chest imaging within the previous 24 months;

      4. The individual’s predicted FVC ≥45%;

      5. The individual’s carbon monoxide diffusion capacity (%DLco) is between 30% to less than 80% predicted; AND

      6. The individual does NOT meet any of the following:

         1. A diagnosis of idiopathic pulmonary fibrosis (IPF);

         2. Significant pulmonary hypertension;

         3. Relevant airway obstruction (i.e. pre-bronchodilator FEV1/FVC <0.7);

         4. Greater than 1.5 times the upper limit of normal for ALT, AST, or bilirubin;

         5. Known risk or predisposition to bleeding;

         6. Receiving full dose anticoagulation treatment; OR

         7. Recent history of MI or stroke;

4. The individual will not be using the requested agent in combination with another agent included in this medical policy;

5. The individual does not have any FDA labeled contraindications to the requested agent; AND

6. The prescribed dosage is within the program quantity limits based on FDA approved labeled dosage.

Length of Approval: 12 months

Renewal Evaluation

Continuation of Esbriet (pirfenidone), Ofev (nintedanib), or Tyenne (tocilizumab-aazg) is medically necessary when ALL of the following criteria are met:

1. The individual has been approved for the requested agent for treatment of the same condition previously through the BCBSMS PA process;

2. The individual has documented clinical improvement (i.e. slowing of disease progression or decrease in symptom severity and/or frequency);

3. The individual will not be using the requested agent in combination with another agent included in this medical policy;

4. The individual does not have any FDA-labeled contraindication(s) to therapy with the requested agent; AND

5. The prescribed dosage is within the program quantity limits based on FDA approved labeled dosage. 

Length of Approval: 12 months

Services related to delivery and/or administration of a medication which have not been approved through the BCBSMS PA review process will be considered not medically necessary.

POLICY EXCEPTIONS

State Health Plan (State and School Employees): The prescription drug(s) in this medical policy may be covered under a prescription drug benefit plan administered by the State Health Plan’s Pharmacy Benefit Manager. Please perform a formulary drug search at https://www.dfa.ms.gov/cvs-caremark and submit any required Prior Authorization Requests for coverage determination to the Plan’s Pharmacy Benefit Manager. Services related to delivery and/or administration of a medication determined to be not medically necessary will also be considered not medically necessary. Services related to delivery and/or administration of a self-administered drug are not covered.

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

Medication failure is defined as disease progression despite maximally tolerated dose (≥3 months use) as appropriate for disease state being treated. Experience of common side effects of medication will not be considered medication failure for the purpose of this review.

Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Mental Health Disorders, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:

1. consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and 

2. appropriate with regard to standards of good medical practice; and

3. not solely for the convenience of the Member, his or her Provider; and

4. the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.

For the definition of Medically Necessary, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary.

POLICY HISTORY

06/15/2016: New policy L.5.01.493 added. Effective 01/01/2016.

11/01/2016: Approved by Pharmacy & Therapeutics (P&T) Committee.

11/14/2017: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee.

11/01/2018: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee. Added drug names to the top of the policy. Added policy statement that the use of samples by a Member will not be considered current or stable therapy for purposes of Medical Policy review.

07/31/2020: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee. Added statement to perform a formulary drug search on the patient's member ID to ensure the prescription drug is covered under their benefit plan. The medication(s) in this medical policy may not be covered under a specific member's benefit plan. Policy description updated regarding causes and risk factors of idiopathic pulmonary fibrosis. Updated FDA approved indications. Policy statements updated to add "pirfenidone" and "nintedanib." Medically necessary criteria updated to add the following: 1) The patient is >18 years of age; 2) If female, the patient is not pregnant; and 3) The patient has a diagnosis of idiopathic pulmonary fibrosis (IPF) verified by a pulmonologist, radiologist, and a pathologist experienced in the diagnosis of interstitial lung disease. Policy Guidelines updated to define medication failure. Sources updated.

02/01/2023: Policy Exceptions updated to add the following: State Health Plan (State and School Employees): The prescription drug(s) in this medical policy may be covered under a prescription drug benefit plan administered by the State Health Plan’s Pharmacy Benefit Manager. Please perform a formulary drug search at  https://www.dfa.ms.gov/cvs-caremark and submit any required Prior Authorization Requests for coverage determination to the Plan’s Pharmacy Benefit Manager. Services related to delivery and/or administration of a medication determined to be not medically necessary will also be considered not medically necessary. Services related to delivery and/or administration of a self-administered drug are not covered.

10/01/2024: Policy reviewed and approved by the Pharmacy & Therapeutics (P&T) Committee. Policy title changed from "Idiopathic Pulmonary Fibrosis" to "Interstitial Lung Disease." Policy updated to add Actemra (tocilizumab). Policy description extensively revised regarding interstitial lung disease. Added indications for Tocilizumab (Actemra). Policy statements updated to include Actemra (tocilizumab) and to revise medically necessary criteria. Policy Guidelines updated to change "Nervous/Mental Conditions" to "Mental Health Disorders" and to remove investigative definition. Sources updated. Effective 12/01/2024.

11/01/2024: Effective 01/01/2025 - Policy description updated to remove "Actemra" and add related medical policies. Revised policy statement to state that the use of samples by an individual will not be considered current or stable therapy to satisfy Medical Policy requirements. Policy statements updated to remove Actemra (tocilizumab). Added Tyenne (tocilizumab-aazg) as medically necessary when the listed criteria are met. Updated policy statement to state that Actemra (tocilizumab) and Tofidence (tocilizumab-bavi) are not covered on any BCBSMS Formulary. Added that services related to delivery and/or administration of a medication which have not been approved through the BCBSMS PA review process will be considered not medically necessary. Sources updated. Code Reference section updated to add HCPCS code Q5135 to the Covered Codes table. Added HCPCS codes J3262 and Q5133 to the Not Covered/Non-Formulary Codes table. Policy update effective 01/01/2025.

09/09/2025: Policy reviewed and approved by the Pharmacy & Therapeutics (P&T) Committee. Policy description updated regarding indications for Tocilizumab. Initial criteria updated regarding immunomodulatory agents, FDA labeled contraindications, and dose requirements. Renewal criteria updated to change "authorization process" to "BCBSMS PA process." Sources updated.

SOURCE(S)

1. Actemra prescribing information. Genentech, Inc. November 2024. Last accessed June 2025.

2. Cottin V, Wollin L, Fischer A, et al. Fibrosing interstitial lung diseases: knowns and unknowns. Eur Respir Rev 2019; 28: 180100 [ https://doi.org/10.1183/16000617.0100-2018 ].

3. Esbriet prescribing information. Genentech, Inc. November 2024. Last accessed June 2025.

4. Khanna, D. et al. “Long-Term Safety and Efficacy of Tocilizumab in Early Systemic Sclerosis–Interstitial Lung Disease: Open-Label Extension of a Phase 3 Randomized Controlled Trial.” Am J Respir Crit Care Med. 2022 Mar 15;205(6):674-684. doi: 10.1164/rccm.202103-0714OC.

5. King TE. Approach to the adult with interstitial lung disease: Clinical evaluation. In: UpToDate, Connor RF (Ed), Wolters Kluwer. (Accessed on June 25, 2025). Available at: https://www.uptodate.com/contents/approach-to-the-adult-with-interstitial-lung-disease-clinical-evaluation

6. King TE. Clinical manifestations and diagnosis of idiopathic pulmonary fibrosis. In: UpToDate, Connor RF (Ed), Wolters Kluwer. (Accessed on June 25, 2025). Available from: https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-idiopathic-pulmonary-fibrosis

7. Lee JS, Montesi S. Overview of the management of adults with interstitial lung disease. In: UpToDate, Connor RF (Ed), Wolters Kluwer. (Accessed on June 25, 2025). Available at: https://www.uptodate.com/contents/overview-of-the-management-of-adults-with-interstitial-lung-disease

8. Ofev prescribing information. Boehringer Ingelheim Pharmaceuticals, Inc. April 2025. Last accessed June 2025.

9. Raghu, G. et al. “Treatment of Systemic Sclerosis-associated Interstitial Lung Disease: Evidence-based Recommendations. An Official American Thoracic Society Clinical Practice Guideline.” Am J Respir Crit Care Med. 2024 Jan 15;209(2):137-152. doi: 10.1164/rccm.202306-1113ST.

10. Tofidence prescribing information. Biogen MA Inc. March 2025. Last accessed June 2025.

11. Tyenne prescribing information. Fresenius Kabi USA, LLC. December 2024. Last accessed June 2025.

12. Varga J, Montesi S. Treatment and prognosis of interstitial lung disease in systemic sclerosis (scleroderma). In: UpToDate, Connor RF (Ed), Wolters Kluwer. (Accessed on June 25, 2025). Available from: https://www.uptodate.com/contents/treatment-and-prognosis-of-interstitial-lung-disease-in-systemic-sclerosis-scleroderma

CODE REFERENCE

This may not be a comprehensive list of procedure codes applicable to this policy.

The code(s) listed below are ONLY medically necessary if the procedure is performed according to the "Policy" section of this document.

Covered Codes

Not Covered/Non-Formulary Codes

CPT copyright American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.