Idiopathic Pulmonary Fibrosis Prior Authorization with Quantity Limit Program Summary

This prior authorization applies to Blue Partner, Commercial, NetResults A series, SourceRx and Health Insurance Marketplace formularies.

 

OBJECTIVE

The intent of the Idiopathic Pulmonary Fibrosis Prior Authorization (PA) Program is to promote appropriate selection of patients for therapy according to product labeling and/or clinical guidelines and/or clinical studies. Criteria will approve doses that are at or below the maximum FDA labeled dose.  Doses above the program set limit will be approved if the requested quantity is below the FDA limit and cannot be dose optimized.  When the quantity is above the FDA limit, the prescriber must submit documentation in support of therapy for the higher dose for the intended diagnosis.

TARGET AGENTS

Esbriet^® (pirfenidone)

Ofev^® (nintedanib)

QUANTITY LIMIT TARGET AGENTS- RECOMMENDED LIMITS

Brand (generic)	GPI	Multisource Code	Quantity per Day Limit
Esbriet (pirfenidone)
267 mg capsules	45550060000120	M, N, O, or Y	6 capsules
267 mg tablets	45550060000325	M, N, O, or Y	6 tablets
801 mg tablets	45550060000345	M, N, O, or Y	3 tablets
Ofev (nintedanib)
100 mg capsules	45554050200120	M, N, O, or Y	2 capsules
150 mg capsules	45554050200130	M, N, O, or Y	2 capsules

PRIOR AUTHORIZATION CRITERIA FOR APPROVAL

Initial Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1.  ONE of the following:

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

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

AND

2. The patient has no known explanation for interstitial lung disease (e.g. radiation, sarcoidosis, hypersensitivity pneumonitis, bronchiolitis obliterans organizing pneumonia, human immunodeficiency virus (HIV), viral hepatitis, and cancer)

AND

3. The patient has undergone serological testing to exclude any connective tissue disease known to cause interstitial lung disease (e.g. scleroderma, polymyositis/dermatomyositis, systemic lupus erythematosus, and rheumatoid arthritis)

AND

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

AND

5. ONE of the following:
   1. ALL of the following:
      1. The patient has usual interstitial pneumonia (UIP) patterns on high-resolution computed tomography (HRCT) scans [containing BOTH of the following features: 1) subpleural, basal predominance 2) honeycombing with or without traction bronchiectasis]

AND

1. 1. 2. The patient does NOT have the presence of any of the following on HRCT:
         1. CT features (i.e. cysts, marked mosaic attenuation, predominant ground glass opacities, profuse micronodules, centrilobular nodules, nodules, consolidation)
         2. Predominant distribution (i.e. peribronchovascular, perilymphatic, upper or mid-lung)
         3. Pleural plaques
         4. Dilated esophagus
         5. Distal clavicular erosions
         6. Extensive lymph node enlargement
         7. Pleural effusions, pleural thickening

AND

1. 1. 3. A pulmonologist and a radiologist, both experienced in the diagnosis of interstitial lung disease, have been consulted with and both determine that the patient has definitive IPF

OR

1. 2. ALL of the following:
      1. The patient has probable UIP patterns on HRCT (i.e. subpleural, basal predominance; reticular pattern with peripheral traction bronchiectasis or bronchiolectasis; may have mild ground-glass opacities)

AND

0. 1. 2. ONE of the following:
1. The patient has had a surgical lung biopsy that demonstrates UIP pattern on histopathology [containing ALL of the following 4 features: 1) Dense fibrosis with architectural distortion [i.e. destructive scarring and/or honeycombing] 2) predominantly subpleural and/or paraseptal distribution of fibrosis 3) presence of patchy involvement of lung parenchyma by fibrosis 4) presence of fibroblast foci]

OR

B. The patient has had a surgical lung biopsy that demonstrates    probable UIP pattern on histopathology [containing ONE of the         following features: 1) some of the features listed for UIP patterns on histopathology noted above but to an extent that     precludes a definite diagnosis AND absence of features to suggest an alternative diagnosis; OR 2) honeycombing alone]. AND

1. 1. 3. The patient does NOT have the presence of any of the following:
         1. Features of other histologic patterns of idiopathic interstitial pneumonia (e.g. absence of fibroblast foci or loose fibrosis) in all biopsies
         2. Histological findings indicative of an alternative diagnosis (e.g. hypersensitivity pneumonitis, Langerhans cell histiocytosis, sarcoidosis, lymphangioleiomyomatosis)

AND

1. 1. 4. A pulmonologist, radiologist, and a pathologist all experienced in the diagnosis of interstitial lung disease have been consulted with and determined that the patient has definitive IPF

                                       OR

1. 3. ALL of the following:
      1. The patient has indeterminate UIP patterns on HRCT (i.e. subpleural, basal predominance; subtle reticulation [may have mild ground-glass opacities or distortion]; CT features and/or distribution of lung fibrosis that do not suggest any specific etiology)

AND

1. 1. 2. The patient has had a surgical lung biopsy that demonstrates UIP pattern on histopathology [containing ALL of the following 4 features: 1) Dense fibrosis with architectural distortion [i.e. destructive scarring and/or honeycombing] 2) predominantly subpleural and/or paraseptal distribution of fibrosis 3) presence of patchy involvement of lung parenchyma by fibrosis 4) presence of fibroblast foci]

AND

1. 1. 3. The patient does NOT have the presence of any of the following:
         1. Features of other histologic patterns of idiopathic interstitial pneumonia (e.g. absence of fibroblast foci or loose fibrosis) in all biopsies
         2. Histological findings indicative of an alternative diagnosis (e.g. hypersensitivity pneumonitis, Langerhans cell histiocytosis, sarcoidosis, lymphangioleiomyomatosis)

AND

1. 1. 4. A pulmonologist, radiologist, and a pathologist all experienced in the diagnosis of interstitial lung disease have been consulted with and determined that the patient has definitive IPF

OR

2. The patient has another FDA approved indication for the requested agent

AND

2. ONE of the following:
   1. The patient is NOT currently being treated with another agent included in this prior authorization program

OR

1. 2. The patient is currently being treated with another agent included in this prior authorization program AND will discontinue prior to starting the requested agent

         AND

3. The patient does not have any FDA labeled contraindications to the requested agent

         AND

4. ONE of the following:
   1. The requested quantity (dose) does NOT exceed the program quantity limit

OR

1. 2. ALL of the following:
      1. The requested quantity (dose) is greater than the program quantity limit

  AND

1. 1. 2. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication

  AND

1. 1. 3. The requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does not exceed the program quantity limit

OR

1. 3. ALL of the following:
      1. The requested quantity (dose) is greater than the program quantity limit

AND

1. 1. 2. The requested quantity (dose) is greater than the maximum FDA labeled dose for the requested indication

AND

1. 1. 3. The prescriber has submitted documentation in support of therapy with a higher dose for the requested indication

Length of Approval: 12 months

Renewal Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. The patient has been previously approved for the requested agent through the Prime Therapeutics Prior Authorization process

AND

2. The patient has had clinical benefit with the requested agent

          AND

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

      AND

4.  ONE of the following:

1. The patient is NOT currently being treated with another agent included in this prior authorization program

OR

2. The patient is currently being treated with another agent included in this prior authorization program AND will discontinue prior to continuing the requested agent

AND

5. The patient does not have any FDA labeled contraindications to the requested agent

    AND                                                         

6. ONE of the following:

1. The requested quantity (dose) does NOT exceed the program quantity limit

OR

2. ALL of the following:

1. The requested quantity (dose) is greater than the program quantity limit

  AND

2. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication

  AND

3. The requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does not exceed the program quantity limit

OR

3. ALL of the following:

1. The requested quantity (dose) is greater than the program quantity limit

   AND

2. The requested quantity (dose) is greater than the maximum FDA labeled dose for the requested indication

   AND

3. The prescriber has submitted documentation in support of therapy with a higher dose for the requested indication

Length of Approval:  12 months

FDA APPROVED INDICATIONS AND DOSAGE^1,2

Agents	FDA Labeled Indications	Dosing and Administration
Esbriet® (pirfenidone) tablet, capsule	Indicated for the treatment of idiopathic pulmonary fibrosis (IPF)	Recommended dosage: 801 mg three times daily taken with food after 14-day titration
Ofev® (nintedanib) capsule	Indicated for the treatment of idiopathic pulmonary fibrosis (IPF)	Recommended dosage: 150 mg twice daily approximately 12 hours apart taken with food

CLINICAL RATIONALE

Idiopathic pulmonary fibrosis (IPF) is a form of chronic, progressive fibrosing interstitial pneumonia of unknown origin occurring primarily in older adults and is limited to the lungs.^5,6 IPF is associated with the histopathologic and/or radiologic pattern of usual interstitial pneumonia (UIP).^4,6  IPF is characterized by fibroblast foci, featuring vigorous replication of mesenchymal cells and disposition of extracellular matrix. It is thought that repeated episodes of acute lung injury, due to unknown stimulus, leads to wound healing and fibrosis, with loss of lung function.⁷ The natural progression can vary with some patients remaining stable for extended periods of time; some having steady, but rapid progression; and some patients experiencing acute exacerbations.³ Historically, a diagnosis of IPF has been associated with a poor prognosis with many only living for 3-5 years post diagnosis. The estimated prevalence of IPF within the United States has been difficult to establish due to the historical lack of a uniform definition, evolving diagnostic criteria, difference in case finding methodologies and study designs.⁴ The range is between 14-63 per 100,000 population with an annual incidence of approximately 7-16 per 100,000 population.⁴  The lower end of the incidence range includes patients with a more narrow definition of IPF. Patients were required to meet all major and minor American Thoracic Society and European Respiratory Society (ATS/ERS) criteria and had to have definite UIP patterns on high-resolution computed tomography (HRCT) scans. The upper end of the incidence range included patients that met the narrow definition requirements, along with patients with HRCT features of possible UIP.4

Guidelines suggest that IPF be considered in adult patients with unexplained chronic exertional dyspnea, presents with cough, bibasilar inspiratory crackles, and finger clubbing.^43,6 The diagnosis of IPF requires exclusion of other known causes of ILD (e.g., domestic and occupational environmental exposures, connective tissue disease, and drug toxicity), either the presence of a UIP pattern on HRCT in patients not subjected to surgical lung biopsy (SLB) OR specific combinations of HRCT patterns and histopathological patterns in patients subjected to SLB.⁶  Guidelines also recommend serological testing to exclude connective tissues disease.⁶

An accurate diagnosis of IPF is a difficult and challenging process.  The accuracy of the diagnosis increases with an integrated multidisciplinary approach.³ This includes dynamic discussion between pulmonologists, radiologists, and pathologists (when appropriate) who are experienced in the diagnosis of interstitial lung disease (ILD).³ The 2018 update of the 2011 guidelines provides a new diagnostic algorithm and schema for correlating histologic and radiologic findings in patients with suspected IPF. Aspects of this algorithm included criteria for four diagnostic categories for patterns of UIP based on HRCT findings (UIP pattern, probable UIP pattern, indeterminate pattern, and alternative diagnosis) and four levels of certainty for histopathologic diagnosis (UIP, probable UIP, indeterminate for UIP, and alternative diagnosis).⁶ Below in Table 4 and 5 are the current guidelines on diagnosis IPF with HRCT and SLB.⁶

UIP is characterized on HRCT by the presence of honeycombing, traction bronchiectasis, and traction bronchiolectasis, which may have concurrent fine reticulation and ground-glass opacification. Honeycombing is must be present for a definitive HRCT diagnosis of UIP. Honeycombing is manifested on HRCT as clustered cystic airspaces, typically of comparable diameters (3–10 mm but occasionally larger). It is usually subpleural and is characterized by well-defined walls. Traction bronchiectasis/bronchiolectasis is another key feature of IPF and ranges from subtle irregularity and non-tapering to marked airway distortion and varicosity.  Ground-glass opacifications superimposed on a fine reticular pattern represents fibrosis and may be seen in patients with IPF. The distribution of UIP on HRCT is characteristically basal and peripheral, though often patchy. The presence of coexistent pleural abnormalities (noted in the alternative diagnosis section in table 4 above) should lead to consideration of an alternative diagnosis. If HRCT patterns show probably or indeterminate UIP, the 2018 guidelines recommend surgical lung biopsy to make a definitive diagnosis. In patients whose HRCT does not demonstrate a UIP pattern, the surgical lung biopsy may still demonstrate UIP pattern on histopathology.⁶ Figure 8 below shows the algorithm for diagnosis with the updated guidelines.

Prior to the simultaneous approvals of Esbriet (pirfenidone) and Ofev (nintedanib), there was no FDA approved pharmacologic therapy for idiopathic pulmonary fibrosis.  The updated ATS/ERS/JRS/ALAT (American Thoracic Society), European Respiratory Society (ERS), Japanese Respiratory Society (JRS), and Latin American Thoracic Society (ALAT) clinical practice guidelines address nintedanib and pirfenidone treatment for IPF.  The guidelines suggest that clinicians use nintedanib or pirfenidone in patients with IPF (conditional recommendation, moderate confidence in estimates of effects).  As with other interventions, the available evidence focuses on patients with IPF with mild to moderate impairment in pulmonary function tests; it is unknown whether the therapeutic benefits would differ in patients with a more severe impairment in pulmonary function testing or those with other comorbidities. The evidence does not allow suggestions about the optimal duration of therapy, and it is unknown how long the treatment effect endures with ongoing drug therapy.⁵

Currently, there are neither head-to-head trials comparing the two agents nor are there any studies using the two in combination for therapy.  Neither agent showed a significant mortality benefit compared to placebo.

Safety^1,2

Neither Esbriet nor Ofev have any FDA labeled contraindications.

REFERENCES

1. Esbriet prescribing information. Genentech. October 2017.
2. Ofev prescribing information. Boehringer Ingelheim. January 2018.
3. An Official American Thoracic Society/European Respiratory Society Statement: Update of the International Multidisciplinary Classification of the Idiopathic Interstitial Pneumonias. Am J Respir Crit Care Med Vol 188, Iss. 6, pp 733–748, Sep 15, 2013. http://www.thoracic.org/statements/resources/interstitial-lung-disease/classification-of-IIPs.pdf.
4. Incidence and prevalence of idiopathic pulmonary fibrosis: review of the literature. Eur Respir Rev. 2012 Dec 1;21(126):355-61. doi: 10.1183/09059180.00002512. http://err.ersjournals.com/content/21/126/355.long.
5. American Thoracic Society Documents: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline: Treatment of Idiopathic Pulmonary Fibrosis- An Update of the 2011 Clinical Practice Guideline. Am J Resp Crit Care 2015; 192(2): e3-e19.  Available at: http://www.thoracic.org/statements/resources/interstitial-lung-disease/IPF-Full-length.pdf.
6. Raghu, G., et al (2018, September 1). Diagnosis of Idiopathic Pulmonary Fibrosis An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. American Journal of Respiratory and Critical Care Medicine, 198(5), 44-68. doi:10.1164/rccm.201807-1255ST.
7. Gross TJ, Hunninghake GW. Idiopathic pulmonary fibrosis. N Engl J Med 2001; 345:517.

This pharmacy policy is not an authorization, certification, explanation of benefits or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All pharmacy policies are based on (i) information in FDA approved package inserts (and black box warning, alerts, or other information disseminated by the FDA as applicable); (ii) research of current medical and pharmacy literature; and/or (iii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

The purpose of pharmacy policies are to provide a guide to coverage. Pharmacy policies are not intended to dictate to physicians how to practice medicine. Physicians should exercise their medical judgment in providing the care they feel is most appropriate for their patients.

Neither this policy, nor the successful adjudication of a pharmacy claim, is guarantee of payment.

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