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ph-1134

Ophthalmic Immunomodulators Prior Authorization with Quantity Limit Program Summary

Policy Number: PH-1134

POLICY REVIEW CYCLE

Effective Date	Date of Origin
10/1/2022

FDA APPROVED INDICATIONS AND DOSAGE

Agent(s)	FDA Indication(s)	Notes	Ref#
Cequa™ (cyclosporine) Ophthalmic solution	Increase tear production in patients with keratoconjunctivitis sicca (dry eye)		1
Verkazia^® (cyclosporine) Ophthalmic emulsion	Treatment of vernal keratoconjunctivitis (VKC) in children and adults		10
Restasis^® (cyclosporine)* Ophthalmic emulsion	Indicated to increase tear production in patients whose tear production is presumed to be suppressed due to ocular inflammation associated with keratoconjunctivitis sicca. Increased tear production was not seen in patients currently taking topical anti-inflammatory drugs or using punctal plugs.	* - generic equivalent available	2
Xiidra™ (lifitegrast) Ophthalmic solution	Treatment of the signs and symptoms of dry eye disease		3

See package insert for FDA prescribing information: https://dailymed.nlm.nih.gov/dailymed/index.cfm

CLINICAL RATIONALE

Dry Eye Disease

Dry eye disease (also known as dry eye syndrome) is a group of tear film disorders due to reduced tear production or tear film instability, associated with ocular discomfort and/or visual symptoms and inflammatory disease of the ocular surface. The tear film secreting glands and ocular surface function as an integrated system. Disease or dysfunction of this system results in unstable and poorly maintained tear film that causes symptoms of ocular irritation and possible damage to the ocular surface. Dry eye disease may be exacerbated by systemic medications (e.g., diuretics, antihistamines, anticholinergics, systemic retinoids, antidepressants) and rosacea.(4)

Dry eye disease is often associated with Sjogren syndrome, an autoimmune multisystem disorder that most often affects the tear and salivary glands. Tear deficiency may occur in other systemic diseases, such as lymphoma, sarcoidosis, hemochromatosis, and amyloidosis. Dry eye disease may also develop due to systemic viral infections, such as retroviruses, Epstein-Barr virus, and HIV.(4)

The American Academy of Ophthalmology and the Tear Film and Ocular Surface Society (TFOS) categorized dry eye into three severity levels based on symptoms and signs. Because of the nature of the disease, the classifications are imprecise as the characteristics overlap between levels of severity.(2,6,7)

Mild dry eye: symptoms of irritation, itching, soreness, ocular discomfort, burning or intermittent blurred vision.
Moderate dry eye: increased discomfort and frequency of symptoms, and negative effect on visual function may become more consistent.
Severe dry eye: increasing frequency of symptoms that may become constant as well as potentially disabling visual symptoms.

The American Academy of Ophthalmology recommend treating mild dry eye with the following:(4,8)

Education and environmental modifications
Elimination of offending topical or systemic medications
Aqueous enhancement using artificial tear substitutes, gels, or ointment
Eyelid therapy (warm compresses and eyelid scrubs)
Treatment of contributing ocular factors such as blepharitis or meibomianitis
Correction of eyelid abnormality

For treatment of moderate dry eye, the following are recommended in addition to mild dry eye treatment options:(4,8)

Topical anti-inflammatory agents (topical cyclosporine and corticosteroids), systemic omega 3 fatty acids supplements
Punctal plugs
Spectacle side shields and moisture chambers

For treatment of severe dry eye, the following are recommended in addition to mild and moderate dry eye treatment options:(4,8)

Systemic cholinergic agonists
Mucolytic agents
Autologous serum tears
Contact lenses
Permanent punctal occlusion
Tarsorrhaphy

Because of the inconsistent correlation between reported symptoms and clinical signs as well as the relatively poor specificity and/or sensitivity of clinical tests, patients with suggestive symptoms without signs should be placed on trial treatments with artificial tears when other potential causes of ocular irritation have been eliminated. As the severity of the dry eyes increases, aqueous enhancement of the eye using topical agents is appropriate. Emulsions, gels, and ointments can be used. The use of artificial tears may be increased, but the practicality of frequent tear instillation depends on the lifestyle or manual dexterity of the patient. Non-preserved tear substitutes are generally preferable; however, tears with preservatives may be sufficient for patients with mild dry eye and an otherwise healthy ocular surface. When tear substitutes are used frequently and chronically (e.g., more than 4 times a day), non-preserved tears are generally recommended.It is imperative to treat any causative factors that are amenable to treatment.(4)

Anti-inflammatory therapies may be considered in addition to aqueous enhancement therapies. However, since dry eye symptoms tend to wax and wane over long periods of time, the lack of long-term data on the effectiveness of cyclosporine and the costs of longer-term (e.g., annual, lifetime) treatment should be weighed.(4)

Pre-treatment with topical ophthalmic corticosteroids either before or during initiation with a non-glucocorticoid anti-inflammatory agent may provide more rapid improvement in symptoms of dry eye disease and decrease the incidence of severe stinging associated with non-glucocorticoid anti-inflammatory agents.(8) The AAO also notes that topical corticosteroid use for dry eye disease is controversial, but use for induction therapy prior to initiating non-glucocorticoid anti-inflammatory agents as maintenance. Steroids can also be used for acute flare-ups triggered by travel, allergies, respiratory infections, or exposures to environmental irritants with maintenance therapy.(9)

The Sjogren’s Syndrome Foundation’s Clinical Practice Guidelines on Ocular Management in Sjögren’s Patients states the following.(5)

Management depends upon the nature of the dry and the severity of disease.
In early disease, tear replacement with topically applied artificial tear or lubricant solutions may be sufficient, but progressive or more severe inflammation of the lacrimal gland and ocular surface occur both as an inciting event in many cases and as a secondary effect as the dry eye disease worsens, called keratoconjunctivitis sicca (KCS), requires the use of dietary supplements (omega 3 essential fatty acids), anti-inflammatory measures (e.g., topical corticosteroids or cyclosporine), or oral secretagogues.
Plugging of the lacrimal puncta can be done once the inflammatory component of dry eye is controlled. Control of lid margin (meibomian gland) disease may require topical antibiotic or systemic doxycycline therapy. The most severe cases of dry eye, particularly those unresponsive to more standard therapy, may require use of topical autologous serum or partial closure of the interpalpebral fissure to reduce surface exposure. Scleral contact lenses may be needed to control severe ocular surface damage

Vernal Keratoconjunctivitis

Vernal keratoconjunctivitis (VKC) is an atopic condition of the external ocular surface. VKC is typically seen in hot, dry climates. Symptoms typically present in early to mid-childhood and typically resolves after puberty. Symptoms may include eye itching, photophobia, tearing, ocular discharge, irritation, redness, and blepharospasm. VKC can be divided into three subcategories based on the presentation of disease, conjunctival, limbal, and mixed presentation. VKC is both an IgE and non-IgE mediated ocular allergic condition.

Treatment follows a step wise approach based on severity of disease.

Topical mast cell stabilizers and antihistamines for patients with micropapillae and no corneal changes
Topical corticosteroids for patients with macropapillae, mucus accumulation, and corneal vascularization
Immunomodulating agents for patients with macropapillae, macroerosion, shield ulcer, and persistent severe inflammation

Topical antihistamines and topical mast cell stabilizers in combination with pulse corticosteroids during an exacerbation is common practice for maintenance of VKC.(11,12)

The American Academy of Ophthalmology Preferred Practice Pattern indicate that topical mast cell stabilizers in combination with topical or oral antihistamines can be used for maintenance. The AAO also recommends topical ophthalmic corticosteroids for acute exacerbations to control severe symptoms and signs. Topical cyclosporine may allow for reduced used of topical steroids.(12)

Safety(1-3,10)

Restasis (cyclosporine) is contraindicated in those with hypersensitivity to any of the ingredients in the formulation.

Xiidra (lifitegrast) is contraindicated in those with known hypersensitivity to lifitegrast or to any of the other ingredients in the formulation.

Cequa (cyclosporine) and Verkazia (cyclosporine) do not have any FDA labeled contraindications for use.

REFERENCES

Number	Reference
1	Cequa prescribing information. Sun Pharma Global. September 2019.
2	Restasis prescribing information. Allergan, Inc. July 2017.
3	Xiidra prescribing information. Shire US, Inc. June 2020.
4	Dry eye syndrome Preferred Practice Pattern. American Academy of Ophthalmology. October 2018. Available at: https://www.aaojournal.org/article/S0161-6420(18)32650-2/pdf Accessed 3/12/2019.
5	Ocular Management in Sjögren’s Patients. Sjögren’s Syndrome Foundation’s Clinical Practice Guidelines. Available at https://www.sjogrens.org/files/research/OcularCPG.pdf. Accessed 3/12/19
6	Craig JP et al. TFOS DEWS II definition and classification report. Ocul Surf. 2017;15(3):276-283.
7	Wolffsohn JS et al. TFOS DEWS II diagnostic methodology report. Ocul Surf. 2017;15(3):539-574.
8	Jones L et al. TFOS DEWS II management and therapy report. Ocul Surf. 2017;15(3):575-628.
9	Weiner, G. (2016, May 05). Savvy steroid use. Retrieved March 10, 2021, from https://www.aao.org/eyenet/article/savvy-steroid-use
10	Verkazia prescribing information. Santen Inc. June 2021.
11	Kraus, C. L. (2018, January 17). Vernal Keratoconjunctivitis. American Academy of Ophthalmology. https://www.aao.org/disease-review/vernal-keratoconjunctivitis-5.
12	Preferred Practice Pattern: Conjunctivitis. American Academy of Ophthalmology. 2018. Accessed June 2021 at: https://www.aao.org/preferred-practice-pattern/conjunctivitis-ppp-2018

POLICY AGENT SUMMARY PRIOR AUTHORIZATION

Agent Names	Strength	Targeted MSC	Available MSC	Effective Date

CEQUA*cyclosporine (ophth) soln	0.09 %	M ; N ; O ; Y	N
RESTASIS (cyclosporine (ophth) emulsion ) ; RESTASIS MULTIDOSE (cyclosporine (ophth) emulsion )	0.05 %	M ; N ; O ; Y	O
RESTASIS*Cyclosporine (Ophth) Emulsion 0.05%	0.05 %	M ; N ; O ; Y	N ; O
VERKAZIA*Cyclosporine (Ophth) Emulsion 0.1%	0.1 %	M ; N ; O ; Y	N
XIIDRA*lifitegrast ophth soln	5 %	M ; N ; O ; Y	N

POLICY AGENT SUMMARY QUANTITY LIMIT

Target Agent GPI	Agent Names	Strength	QL Amount	Dose Form	Days Supply	Duration	Addtl QL Info	Allowed Exceptions	Targeted NDCs When Exclusions Exist	Effective Date

86720020002040	CEQUA (cyclosporine (ophth) soln )	0.09 %	60.0	VIALS	30	Days
86720020001620	RESTASIS (cyclosporine (ophth) emulsion )	0.05 %	60.0	VIALS	30	Days			00023-9163-30 ; 00023-9163-60 ; 50090-1242-00
86720020001620	RESTASIS (cyclosporine (ophth) emulsion ) ; RESTASIS MULTIDOSE (cyclosporine (ophth) emulsion )	0.05 %	1.0	BOTT	30	Days			00023-5301-05 ; 50090-4476-00
86720020001630	VERKAZIA*Cyclosporine (Ophth) Emulsion 0.1%	0.1 %	120.0	VIALS	30	Days
86734050002020	XIIDRA (lifitegrast ophth soln )	5 %	60.0	VIALS	30	Days

CLIENT SUMMARY – PRIOR AUTHORIZATION

Agent Names	Strength	Client Formulary
CEQUA*cyclosporine (ophth) soln	0.09 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx
RESTASIS (cyclosporine (ophth) emulsion ) ; RESTASIS MULTIDOSE (cyclosporine (ophth) emulsion )	0.05 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx
RESTASIS*Cyclosporine (Ophth) Emulsion 0.05%	0.05 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx
VERKAZIA*Cyclosporine (Ophth) Emulsion 0.1%	0.1 %
XIIDRA*lifitegrast ophth soln	5 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx

CLIENT SUMMARY – QUANTITY LIMITS

Agent Names	Strength	Client Formulary
CEQUA (cyclosporine (ophth) soln )	0.09 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx
RESTASIS (cyclosporine (ophth) emulsion )	0.05 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx
RESTASIS (cyclosporine (ophth) emulsion ) ; RESTASIS MULTIDOSE (cyclosporine (ophth) emulsion )	0.05 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx
VERKAZIA*Cyclosporine (Ophth) Emulsion 0.1%	0.1 %
XIIDRA (lifitegrast ophth soln )	5 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; SourceRx

PRIOR AUTHORIZATION CLINICAL CRITERIA FOR APPROVAL

Module	Clinical Criteria for Approval
	Initial Evaluation Restasis (cyclosporine ophthalmic emulsion) will be approved when ALL of the following are met: ONE of the following: ALL of the following: The patient has a diagnosis of dry eye disease (i.e., dry eye syndrome, keratoconjunctivitis sicca [e.g., Sjögren’s Syndrome]) AND The patient will NOT be using the requested agent in combination with punctal plug(s) AND ONE of the following: The patient has previously tried or is currently using aqueous enhancements (e.g., artificial tears, gels, ointments [target agents not included]) OR The patient has an intolerance or hypersensitivity to aqueous enhancements OR The patient has an FDA labeled contraindication to ALL aqueous enhancements (e.g., artificial tears, gels, ointments [target agents not included]) OR The patient has another FDA approved indication for the requested agent AND The patient will NOT be using the requested agent in combination with another ophthalmic immunomodulator agent (e.g., Restasis, Cequa, Xiidra, Verkazia) or Tyrvaya AND The patient does NOT have any FDA labeled contraindications to the requested agent Length of Approval: 6 months NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria Initial Evaluation Cequa (cyclosporine), Xiidra (lifitegrast) will be approved when ALL of the following are met: ONE of the following: BOTH of the following: The patient has a diagnosis of dry eye disease (i.e., dry eye syndrome, keratoconjunctivitis sicca [e.g., Sjögren's Syndrome]) AND ONE of the following: The patient has previously tried or is currently using aqueous enhancements (e.g., artificial tears, gels, ointments [target agents not included]) OR The patient has an intolerance or hypersensitivity to aqueous enhancements OR The patient has an FDA labeled contraindication to ALL aqueous enhancements (e.g., artificial tears, gels, ointments [target agents not included]) OR The patient has another FDA approved indication for the requested agent AND The patient will NOT be using the requested agent in combination with another ophthalmic immunomodulator agent (e.g., Restasis, Cequa, Xiidra, Verkazia) or Tyrvaya AND The patient does NOT have any FDA labeled contraindications to the requested agent Length of Approval: 3 months NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria Initial Evaluation Verkazia (cyclosporine) will be approved when ALL of the following are met: ONE of the following: The patient has a diagnosis of vernal keratoconjunctivitis (VKC) AND BOTH of the following: ONE of the following: The patient has tried and had an inadequate response to combination of a topical ophthalmic mast cell stabilizer AND an antihistamine used in the treatment of VKC OR The patient has an intolerance or hypersensitivity to combination of a topical ophthalmic mast cell stabilizer AND an antihistamine used in the treatment of VKC OR The patient has an FDA labeled contraindication to ALL topical ophthalmic mast cell stabilizers AND antihistamines AND ONE of the following: The patient has tried and had an inadequate response to a topical ophthalmic corticosteroid used in the treatment of VKC OR The patient has an intolerance or hypersensitivity to topical ophthalmic corticosteroid therapy OR The patient has an FDA labeled contraindication to ALL topical ophthalmic corticosteroids OR The patient has another FDA approved indication for the requested agent AND The patient will NOT be using the requested agent in combination with another ophthalmic immunomodulator agent (e.g., Restasis, Cequa, Xiidra, Verkazia) or Tyrvaya AND The patient does NOT have any FDA labeled contraindications to the requested agent Length of Approval: 4 months NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria Renewal Evaluation Target Agent(s) will be approved when ALL of the following are met: The patient has been previously approved for the requested agent through the plan’s Prior Authorization process AND The patient has had clinical benefit with the requested agent AND The patient will NOT be using the requested agent in combination with another ophthalmic immunomodulator agent (e.g., Restasis, Cequa, Xiidra, Verkazia) or Tyrvaya AND The patient does NOT have any FDA labeled contraindications to the requested agent Length of Approval: 12 months NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria

Module

Clinical Criteria for Approval

Initial Evaluation

Restasis (cyclosporine ophthalmic emulsion) will be approved when ALL of the following are met:

ONE of the following:
1. ALL of the following:
  1. The patient has a diagnosis of dry eye disease (i.e., dry eye syndrome, keratoconjunctivitis sicca [e.g., Sjögren’s Syndrome]) AND
  2. The patient will NOT be using the requested agent in combination with punctal plug(s) AND
  3. ONE of the following:
    1. The patient has previously tried or is currently using aqueous enhancements (e.g., artificial tears, gels, ointments [target agents not included]) OR
    2. The patient has an intolerance or hypersensitivity to aqueous enhancements OR
    3. The patient has an FDA labeled contraindication to ALL aqueous enhancements (e.g., artificial tears, gels, ointments [target agents not included]) OR
2. The patient has another FDA approved indication for the requested agent AND
The patient will NOT be using the requested agent in combination with another ophthalmic immunomodulator agent (e.g., Restasis, Cequa, Xiidra, Verkazia) or Tyrvaya AND
The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval: 6 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria

Initial Evaluation

Cequa (cyclosporine), Xiidra (lifitegrast) will be approved when ALL of the following are met:

ONE of the following:
1. BOTH of the following:
  1. The patient has a diagnosis of dry eye disease (i.e., dry eye syndrome, keratoconjunctivitis sicca [e.g., Sjögren's Syndrome]) AND
  2. ONE of the following:
    1. The patient has previously tried or is currently using aqueous enhancements (e.g., artificial tears, gels, ointments [target agents not included]) OR
    2. The patient has an intolerance or hypersensitivity to aqueous enhancements OR
    3. The patient has an FDA labeled contraindication to ALL aqueous enhancements (e.g., artificial tears, gels, ointments [target agents not included]) OR
2. The patient has another FDA approved indication for the requested agent AND
The patient will NOT be using the requested agent in combination with another ophthalmic immunomodulator agent (e.g., Restasis, Cequa, Xiidra, Verkazia) or Tyrvaya AND
The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval: 3 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria

Initial Evaluation

Verkazia (cyclosporine) will be approved when ALL of the following are met:

ONE of the following:
1. The patient has a diagnosis of vernal keratoconjunctivitis (VKC) AND BOTH of the following:
  1. ONE of the following:
    1. The patient has tried and had an inadequate response to combination of a topical ophthalmic mast cell stabilizer AND an antihistamine used in the treatment of VKC OR
    2. The patient has an intolerance or hypersensitivity to combination of a topical ophthalmic mast cell stabilizer AND an antihistamine used in the treatment of VKC OR
    3. The patient has an FDA labeled contraindication to ALL topical ophthalmic mast cell stabilizers AND antihistamines AND
  2. ONE of the following:
    1. The patient has tried and had an inadequate response to a topical ophthalmic corticosteroid used in the treatment of VKC OR
    2. The patient has an intolerance or hypersensitivity to topical ophthalmic corticosteroid therapy OR
    3. The patient has an FDA labeled contraindication to ALL topical ophthalmic corticosteroids OR
2. The patient has another FDA approved indication for the requested agent AND
The patient will NOT be using the requested agent in combination with another ophthalmic immunomodulator agent (e.g., Restasis, Cequa, Xiidra, Verkazia) or Tyrvaya AND
The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval: 4 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria

Renewal Evaluation

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

The patient has been previously approved for the requested agent through the plan’s Prior Authorization process AND
The patient has had clinical benefit with the requested agent AND
The patient will NOT be using the requested agent in combination with another ophthalmic immunomodulator agent (e.g., Restasis, Cequa, Xiidra, Verkazia) or Tyrvaya AND
The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval: 12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria

QUANTITY LIMIT CLINICAL CRITERIA FOR APPROVAL

Module	Clinical Criteria for Approval
	Quantity Limit for the Target Agent(s) will be approved when ONE of the following is met: The requested quantity (dose) does NOT exceed the program quantity limit OR ALL of the following: The requested quantity (dose) is greater than the program quantity limit AND The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND The requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does not exceed the program quantity limit Length of Approval: Initial approval: Cequa and Xiidra - 3 months, Verkazia - 4 months, Restasis/cyclosporine - 6 months; Renewal approval 12 months

Module

Clinical Criteria for Approval

Quantity Limit for the Target Agent(s) will be approved when ONE of the following is met:

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

Length of Approval: Initial approval: Cequa and Xiidra - 3 months, Verkazia - 4 months, Restasis/cyclosporine - 6 months; Renewal approval 12 months

This program applies to Blue Partner, Commercial, GenPlus, SourceRx and Health Insurance Marketplace formularies.

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 Blue Cross and Blue Shield of Alabama’s 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.

BCBSAL _ PS _ Ophthalmic Immunomodulators Prior Authorization with Quantity Limit _ProgSum_ 10/1/2022 _