Medicare Advantage

Medical Policy

Notification

Intravenous Infliximab and Related Biosimilars

Notification Issue Date:

This version of the policy will become effective 03/21/2022.

This policy has been updated to communicate the addition of the Company's preferred product designation. Preferred products include Infliximab (Remicade), unbranded Infliximab, and infliximab-dyyb (Inflectra). Non-preferred products include infliximab-abda (Renflexis), infliximab-axxq (Avsola), and infliximab-qbtx (Ixifi).

Title:

Intravenous Infliximab and Related Biosimilars

Policy #:

MA08.019q

Policy

The Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition.

In the absence of coverage criteria from applicable Medicare statutes, regulations, NCDs, LCDs, CMS manuals, or other Medicare coverage documents, this policy uses internal coverage criteria developed by the Company in consideration of peer-reviewed medical literature, clinical practice guidelines, and/or regulatory status.

INDEX OF MEDICALLY NECESSARY INDICATIONS

This policy addresses numerous medically necessary indications for the use of intravenous infliximab (Remicade) and related biosimilars (e.g., unbranded infliximab, infliximab-abda [Renflexis], infliximab-axxq [Avsola], infliximab-dyyb [Inflectra], (listed in order of appearance within the Policy section). Please see below for the specific medical necessity criteria. (NOTE: Experimental/Investigational section below must also be reviewed).

RHEUMATOLOGIC CONDITIONS	Ankylosing spondylitis and nonradiographic axial spondyloarthritis Autoimmune collagen vascular disease Behçet syndrome Inflammatory bowel disease arthritis Polyarticular juvenile idiopathic arthritis (JIA) Psoriatic arthritis Reactive arthritis (Reiter disease) Rheumatoid arthritis (RA) Sarcoidosis Uveitis, noninfectious, due to Behçet syndrome Uveitis, noninfectious, not due to Behçet syndrome
GASTROINTESTINAL INDICATIONS	Crohn disease: non-fistulizing Crohn disease: fistulizing Ulcerative colitis
DERMATOLOGIC INDICATIONS	Hidradenitis suppurativa Plaque psoriasis Pyoderma gangrenosum
HEMATOPOIETIC CELL TRANSPLANTATION	Acute graft-versus-host disease (aGVHD)
IMMUNOTHERAPY-RELATED TOXICITY INDICATIONS	Cardiac toxicities Diarrhea or colitis Elevated serum creatinine/acute renal failure inflammatory arthritis Pneumonitis Uveitis

MEDICALLY NECESSARY

Intravenous infliximab (Remicade) and related biosimilars (e.g., unbranded infliximab, infliximab-abda [Renflexis], infliximab-axxq [Avsola], infliximab-dyyb [Inflectra], are considered medically necessary and, therefore, covered when the individual meets all of the requirements in the following sections:

Dosing and frequency requirements listed in Attachment A
Indications and all the criteria are met

RHEUMATOLOGIC CONDITIONS

Ankylosing spondylitis and nonradiographic axial spondyloarthritis
- When all of the following criteria are met:
  - Individual is over 18 years of age with evidence of active disease (increasing inflammation, pain, disability, and decreased function)
  - Documentation of an adequate therapeutic trial* of at least two nonsteroidal anti-inflammatory drugs (NSAIDs) that have failed to control symptoms
- If the above criteria are not met, there must be documentation both of very severe disease and that the clinician considers infliximab or related biosimilars the best initial drug of choice with appropriate justification (severe pain, disability, and inability to perform activities of daily [ADLs], or severe impact on quality of life)

Autoimmune collagen vascular disease
- Consideration may be given for individuals with an autoimmune collagen vascular disease that is refractory to conventional therapies.

Behçet syndrome

Documented failure, contraindication, or intolerance to conventional therapy, such as: corticosteroids, colchicine, or disease-modifying antirheumatic drugs (DMARDs) (e.g., azathioprine, cyclosporine, other tumor necrosis factor [TNF] inhibitors)

Inflammatory bowel disease arthritis
- When all of the following criteria are met:
  - Individual is over 18 years of age with evidence of active disease (increased disease activity evidenced by increasing inflammation, pain, disability, and decreased function)
  - Documented failure, contraindication or intolerance to a 3-month trial of any of the DMARDs (e.g., sulfasalazine, azathioprine, methotrexate, other anti-TNF agents)
- If the above criteria are not met, there must be documentation of very severe disease and the clinician considers infliximab or related biosimilars the best initial drug of choice with appropriate justification (severe pain, disability, and inability to perform ADLs, or severe impact to quality of life)

Polyarticular juvenile idiopathic arthritis (JIA)
- When all of the following criteria are met:
  - Individual is 4 years of age and older with moderate-to-severe polyarticular JIA with evidence of active disease (increased disease activity evidenced by increasing inflammation, pain, disability, and decreased function)
  - Documented failure, contraindication, or intolerance to a 3-month trial of any of the nonbiologic DMARDs (e.g., methotrexate, sulfasalazine, leflunomide)
  - Documented failure, contraindication, or intolerance to a 3-month trial of any of the US Food and Drug Administration (FDA)-approved biologic DMARDs for JIA (e.g., anti-TNF agents, T-cell costimulation modulators)
  - Infliximab or related biosimilars will be used in combination with methotrexate, or as a monotherapy when the individual is intolerant of, or has a contraindication to, methotrexate
- If the above criteria are not met, there must be documentation of both very severe disease and that the clinician considers infliximab or related biosimilars the best initial drug of choice with appropriate justification (severe pain, disability, and inability to perform ADLs, or severe impact on quality of life)

Psoriatic arthritis
- When all the following criteria are met:
  - Individual is over 18 years of age with evidence of active disease (increased disease activity evidenced by increasing inflammation, pain, disability, and decreased function)
  - Documented failure, contraindication, or intolerance to a 3-month trial of any of the DMARDs (e.g., sulfasalazine, azathioprine, cyclosporine, methotrexate, other anti-TNF agents)
- If the above criteria are not met, there must be documentation both of very severe disease and that the clinician considers infliximab or related biosimilars the best initial drug of choice with appropriate justification (severe pain, disability, and inability to perform ADLs, or severe impact to quality of life)

Reactive arthritis (Reiter disease)
- When all the following criteria are met:
  - Individual is over 18 years of age with evidence of active disease (increased disease activity evidenced by increasing inflammation, pain, disability, and decreased function)
  - Documented failure, contraindication, or intolerance to a 3-month trial of any of the DMARDs (e.g., sulfasalazine, methotrexate, other anti-TNF agents)
- If the above criteria are not met, there must be documentation of very severe disease and the clinician considers infliximab or related biosimilars the best initial drug of choice with appropriate justification (severe pain, disability, and inability to perform ADLs, or severe impact to quality of life)

Rheumatoid arthritis (RA)
- When all the following criteria are met:
  - Individual is over 18 years of age with moderate-to-severe RA with evidence of active disease (increased disease activity evidenced by increasing inflammation, pain, disability, and decreased function)
  - Documented failure, contraindication or intolerance to a 3-month trial of any of the DMARDs (e.g., hydroxychloroquine, leflunomide, sulfasalazine, methotrexate, other anti-TNF agents or non-TNF biologics [abatacept, rituximab, tocilizumab])
  - Infliximab or related biosimilars will be used in combination with methotrexate, or as a monotherapy when the individual is intolerant of, or has a contraindication to, methotrexate
- If the above criteria are not met, there must be documentation both of very severe disease and that the clinician considers infliximab or related biosimilars the best initial drug of choice with appropriate justification (severe pain, disability, and inability to perform ADLs, or severe impact on quality of life)

Sarcoidosis
- When both criteria are met:
  - Individual at least 18 years of age
  - Documentation of failure, contraindication, or intolerance to a 3-month trial of a standard regimen of corticosteroids and DMARDs (e.g., methotrexate, azathioprine)
- If the above criteria are not met, there must be documentation both of very severe disease and that the professional provider considers infliximab or related biosimilars to the best initial drug of choice with appropriate justification (disability, and inability to perform ADLs, or severe impact on quality of life)

Uveitis, noninfectious, due to Behçet syndrome
- Documented diagnosis of Behçet disease with vision-threatening uveitis

Uveitis, noninfectious, not due to Behçet syndrome

Documented failure, contraindication, or intolerance to corticosteroids and at least one DMARD (e.g., azathioprine, cyclosporine, methotrexate, mycophenolate, tacrolimus, or other TNF inhibitors)

GASTROINTESTINAL INDICATIONS

Crohn disease (CD): nonfistulizing
- Presence of moderate-to-severe active CD in adults or pediatric individuals 6 years of age or older when all the following criteria are met:
  - The individual has active CD as indicated by any of the following signs or symptoms: gastrointestinal bleeding, weight loss, diarrhea, perianal disease, internal fistula(ae), intestinal obstruction, megacolon or extraintestinal manifestations, such as arthritis or spondylitis
  - The individual has had an inadequate response to conventional therapy (unless intolerant or contraindicated) that include, but are not limited to: antibiotics, 5-aminosalicylates (e.g., mesalamine), DMARDs (e.g., 6-MP [6-MP], azathioprine, corticosteroids)
- Presence of severe inflammatory disease involving the distal small bowel and/or large bowel in an individual who is having symptoms of gastrointestinal bleeding, diarrhea, profound anemia, or poor nutritional intake associated with weight loss or abdominal pain.

Crohn disease: fistulizing
- When both criteria are met:
  - An adult or pediatric individual 6 years of age or older whose presentation of CD involves the formation of a fistula(ae)
  - An adult or pediatric individual 6 years of age or older with diffuse inflammatory disease involving the distal small bowel and/or large bowel who is having symptoms of profound anemia, gastrointestinal bleeding, poor nutritional intake associated with weight loss, or abdominal pain

Ulcerative colitis: adults
- When all the following criteria are met:
  - In individuals 18 years of age or older with moderate-to-severe active ulcerative colitis who have had an inadequate response to conventional therapy, including a documented failure, contraindication, or intolerance to at least two of the following:
    - Aminosalicylates: (e.g., mesalamine [Apriso, Asacol, Canasa, Lialda, Pentasa, Rowasa], sulfasalazine [Azulfidine], olsalazine [Dipentum])
    - Systemic corticosteroids: (e.g., prednisone, prednisolone)
    - DMARDs (e.g., 6-MP, azathioprine [Imuran], or cyclosporine [e.g., Neoral, Gengraf])

When either of the following criteria are met:

In individuals 18 years of age or older, when there is a clinical presentation that requires an intervention with a more immediate effect to resolve the colitis; examples include:

Symptoms of profound anemia, poor nutritional intake associated with weight loss, and abdominal pain
Individuals who have the potential for adverse events to the other, more common treatment regimens or who have contraindication to the use of these treatment regimens (e.g., individuals with underlying diabetes may have worsening control with the addition of prednisone)

If the above criteria are not met, there must be documentation of the individual's rapidly worsening disease as indicated by increasing disability, poorly controlled symptoms, and increasing quality of life concerns (cannot perform ADLs without great difficulty) and there is inadequate response to more conventional agents.

Ulcerative colitis: children
- When all of the following criteria are met:
  - Child is at least 6 years of age
  - Has moderate-to-severe active ulcerative colitis (see Policy Guidelines section)
  - Has had an inadequate response to conventional therapy (e.g., aminosalicylates, azathioprine [AZA, Imuran], 6-MP, or corticosteroids)

DERMATOLOGIC INDICATIONS

Hidradenitis suppurativa
- When all of the following criteria are met:
  - The individual is 18 years of age or older with documentation of moderate-to-severe hidradenitis suppurativa with recurrent abscesses/inflammatory nodules and scar formation.
  - Documentation of failure, contraindication, or intolerance to at least 3 months of antibiotics (e.g., doxycycline, clindamycin, rifampin).
  - Documentation of failure, contraindication, or intolerance to a 3-month trial of any of the FDA-approved biologic DMARDs for hidradenitis suppurativa (e.g., anti-TNF agents, T-cell costimulation modulators).

Plaque psoriasis
- When all the following criteria are met:
  - The individual is 18 years of age or older with chronic, severe psoriasis who is a candidate for systemic therapy but other systemic therapies are less medically appropriate (e.g., presence of other factors such as hypertension, alcohol consumption, the condition of pregnancy, nonmelanoma skin cancers).
  - Individual is affected with plaque psoriasis covering more than 10% of body surface area (BSA) or a lesser percentage if psoriasis affects sensitive body areas, such as hands, feet, face, or genitals.
  - Documentation of failure, contraindication, or intolerance to a trial of at least 3 months with at least one of the following:
    - Phototherapy: either UVB, PUVA
    - Methotrexate (e.g., Trexall, Rheumatrex)
    - Retinoids (e.g., acitretin [Soriatane])
    - Cyclosporine (e.g., Neoral, Gengraf)
- If the above criteria are not met, there must be documentation of severe psoriasis (>10 percent BSA) or a lesser percentage if psoriasis affects sensitive body areas, such as hands, feet, face, or genitals and is very symptomatic (e.g., pain, pruritus, burning, scaling), the symptoms significantly hinder the quality of life, and the use of other systemic therapy is not appropriate due to other factors (e.g., history of hypertension, alcohol consumption, the condition of pregnancy, nonmelanoma skin cancers).

Pyoderma gangrenosum
- In individuals 18 years of age or older with documentation of pyoderma gangrenosum that is refractory to a 3-month trial of conventional treatments, such as local steroid injections, topical tacrolimus, systemic corticosteroids, dapsone, DMARDs (e.g., cyclosporine), and conservative wound care, including oral antibiotics
- If the above criterion is not met, there must be documentation of rapidly worsening disease process as indicated by increasing disability, poorly controlled symptoms, and increasing quality of life concerns (cannot perform ADLs without great difficulty) and who is not adequately responding to more conventional agents.

HEMATOPOIETIC CELL TRANSP

LANTATION

Acute Graft-Versus Host Disease (aGVHD)

Acute GVHD in those who have undergone hematopoietic cell transplantation, as additional therapy in conjunction with systemic corticosteroids and in combination with original immunosuppressive agent (i.e tacrolimus, cyclosporine, methotrexate) following no response (steroid-refractory disease) to first-line therapy options

IMMUNOTHERAPY-RELATED TOXICITY INDICATIONS

Treatment of any of the following immunotherapy-related toxicities as additional immunosuppression
- Cardiac toxicities
  - In individuals with myocarditis if no improvement within 24 to 48 hours of starting pulse-dose methylprednisolone
- Esophagitis
- Diarrhea or colitis
  - In individuals with mild (Grade 1) diarrhea and colitis if persistent or progressive symptoms and positive lactoferrin/calprotectin
  - In individuals with moderate (Grade 2) or severe (Grades 3–4) diarrhea or colitis if colonoscopy or flexible sigmoidoscopy shows significant ulceration or extensive nonulcerative inflammation
- Anemia
- Elevated serum creatinine/acute renal injury
- Inflammatory arthritis
  - In individuals with moderate or severe inflammatory arthritis unable to taper corticosteroids after one week
- Pneumonitis
- Uveitis

EXPERIMENTAL/INVESTIGATIONAL

All other uses for intravenous infliximab and related biosimilars, including use in IgG4-related diseases, are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the medical policy on off-label coverage for prescription drugs and biologics.

DOSING AND FREQUENCY REQUIREMENTS

Refer to Attachment A for dosing and frequency requirements for intravenous infliximab and related biosimilars.

The Company reserves the right to modify the dosing and frequency requirements listed in this policy to ensure consistency with the most recently published recommendations for the use of infliximab and related biosimilars. Changes to these guidelines are based on a consensus of information obtained from resources such as, but not limited to: the FDA; Company-recognized authoritative pharmacology compendia; or published peer-reviewed clinical research. The professional provider must supply supporting documentation (i.e., published peer-reviewed literature) in order to request coverage for an amount of infliximab and related biosimilars outside of the dosing and frequency requirements listed in this policy. For a list of Company-recognized pharmacology compendia, view our policy on off-label coverage for prescription drugs and biologics.

Accurate member information is necessary for the Company to approve the requested dose and frequency of this drug. If the member’s dose, frequency, or regimen changes (based on factors such as changes in member weight or incomplete therapeutic response), the provider must submit those changes to the Company for a new approval based on those changes as part of the precertification process. The Company reserves the right to conduct postpayment review and audit procedures for any claims submitted for infliximab and related biosimilars.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.

When coverage of infliximab and related biosimilars are requested outside of the dosing and frequency requirements listed in this Policy, the prescribing professional provider must supply documentation (i.e., published peer-reviewed literature) to the Company that supports this request.

BILLING REQUIREMENTS

For drugs that have more than one method of administration, application of the JA modifier is required to indicate the route of administration. To report the intravenous route of administration, append the following modifier: JA Administered Intravenously.

Inclusion of a code in this policy does not imply reimbursement. Eligibility, benefits, limitations, exclusions, utilization management/referral requirements, provider contracts, and Company policies apply.

Guidelines

BLACK BOX WARNINGS

Refer to the specific manufacturer's prescribing information for any applicable Black Box Warnings.

THE PEDIATRIC ULCERATIVE COLITIS ACTIVITY INDEX (PUCAI)

The Pediatric Ulcerative Colitis Activity Index, published in 2007 in Gastroenterology, analyzes data that has been obtained from the child through noninvasive means during the previous 48 hours. Elements of this data assessment include the presence of abdominal pain, rectal bleeding, stool consistency, number of stools in 24 hours, presence or absence of nocturnal stools, and the child's activity level.

The Pediatric Ulcerative Colitis Activity Index (PUCAI) Maximum score is 85
Remission	<10
Mild-to-moderate disease	11 to 30
Moderate-to-severe disease	30 to 65
Severe	>65

Turner D,

Otley AR, Mack D, et al. Development, Validation, and Evaluation of a Pediatric Ulcerative Colitis Activity Index: A Prospective Multicenter Study. Gastroenterology. 2007;133(2):423-432.

For complete information on the parameters evaluated in the PUCAI and how it is scored, please see the following table: http://download.lww.com/wolterskluwer_vitalstream_com/PermaLink/MPG/A/MPG_2011_04_25_LEE_201708_SDC1.pdf.

BENEFIT APPLICATION

There is no Medicare coverage determination addressing intravenous infliximab and related biosimilars; therefore, the Company policy is applicable.

Subject to the applicable Evidence of Coverage, intravenous infliximab and related biosimilars are covered under the medical benefits of the Company’s Medicare Advantage products when the medical necessity criteria and dosing and frequency requirements listed in this medical policy are met.

However, services that are identified in this policy as experimental/investigational are not eligible for coverage or reimbursement by the Company.

For Medicare Advantage members, certain drugs are available through either the member's medical benefit (Part B benefit) or pharmacy benefit (Part D benefit), depending on how the drug is prescribed, dispensed, or administered. This medical policy only addresses instances when infliximab (Remicade®) is covered under a member's medical benefit (Part B benefit). It does not address instances when infliximab (Remicade®) is covered under a member's pharmacy benefit (Part D benefit).

INFORMATION FROM THE MANUFACTURER AND THE FDA LABELING

PEDIATRIC USE
Intravenous infliximab and related biosimilars have not been studied in children with Crohn disease or ulcerative colitis younger than 6 years of age. The long-term (duration >1 year) safety and effectiveness of infliximab and related biosimilars in the treatment of Crohn disease or ulcerative colitis for the pediatric population have not been established in clinical trials.

CONTRAINDICATIONS
Intravenous infliximab and related biosimilars at doses greater than 5 mg/kg should not be administered to individuals with moderate to severe heart failure. In a randomized study evaluating infliximab and related biosimilars in individuals with moderate to severe heart failure (New York Heart Association [NYHA] Functional Class III/IV), treatment at 10 mg/kg was associated with an increased incidence of death and hospitalization due to worsening heart failure.

USE WITH ANAKINRA (KINERET®) OR ABATACEPT (ORENCIA®)
The combination of infliximab or related biosimilars with anakinra (

Kineret),

abatacept (

Orencia) and other biological products used to treat the same condition as infliximab or related biosimilars is not recommended.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

The FDA initially approved infliximab (Remicade®) on August 24, 1998. Supplemental approvals have since been issued. The FDA has issued subsequent approvals for biosimilar products.

Description

Infliximab (Remicade) was initially approved by the US Food and Drug Administration (FDA) on August 24, 1998, for rheumatoid arthritis (RA) and Crohn disease (CD). Supplemental approvals have since been issued. The FDA has issued subsequent approvals for biosimilar products. According to the FDA, "a biosimilar product is a biological product that is approved based on a showing that it is highly similar to an FDA-approved biological product, known as a reference product, and has no clinically meaningful differences in terms of safety and effectiveness from the reference product. Only minor differences in clinically inactive components are allowable in biosimilar products." NOTE: Unbranded Infliximab for Injection, made by Janssen, is an unbranded biologic that is the same product as the brand-name product infliximab (Remicade). It is NOT considered a biosimilar.

Infliximab and related biosimilars are chimeric immunoglobulin monoclonal antibodies that bind to and neutralize the effects of tumor necrosis factor-alpha (TNF-α), a naturally occurring cytokine that plays a role in inflammatory and immune responses. Increased concentrations of TNF-α have been found in the affected tissues of individuals with certain anti-inflammatory disease, such as RA, CD, ulcerative colitis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis. Infliximab and related biosimilars are supplied as a sterile, white, lyophilized powder for intravenous (IV) infusion, which is prepared and administered by a professional provider.

Infliximab and related biosimilars is available in two forms: injection for intravenous use and injection for subcutaneous use.

Infliximab and related biosimilars contain anti-TNF-α antibodies that reduce infiltration of inflammatory cells and TNF-α production in affected areas (e.g., the inflamed joints in RA, the inflamed intestines in CD). Infliximab and related biosimilars also initiate healing in areas of erosion and inflammation caused by diseases such as ulcerative colitis and CD. Decreased concentrations of TNF-α may be associated with decreased disease activity; however, the full mechanism of action of infliximab is not thoroughly understood.

Several categories of drugs are used to treat some rheumatic joint diseases that produce chronic inflammation. For many rheumatologic conditions, treatment typically begins with over-the-counter (OTC) drugs referred to as nonsteroidal anti-inflammatory drugs (NSAIDs); these drugs are analgesic, antipyretic, relieve pain without impairing consciousness, and, when given in higher doses, have anti-inflammatory effects. The term "non-steroidal" distinguishes these agents from those that contain steroids whose action is also anti-inflammatory. NSAIDs include, but are not limited to, aspirin, ibuprofen, and naproxen, which are available without a prescription at local retail pharmacies.

Disease-modifying antirheumatic drugs (DMARDs) act to slow down disease progression, and some act with mild chemotherapeutic action, causing immunosuppression. Furthermore, DMARDs can be subdivided into drugs that are the traditional small molecular mass, chemically synthesized nonbiologic DMARDs, such as, but not limited to, methotrexate, sulfasalazine, azathioprine, leflunomide, hydroxychloroquine sulfate, cyclosporine, and biologic DMARDs. Examples of biologic DMARDs include, but are not limited to, etanercept (Enbrel), adalimumab (Humira), anakinra (Kineret), abatacept (Orencia), rituximab (Rituxan), and infliximab (Remicade).

For gastrointestinal or dermatologic manifestations of inflammatory disease, other types of initial treatments are indicated, depending on severity of symptom presentation and degree of disability.

OFF-LABEL INDICATIONS

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of professional clinical guidelines issued by leading professional organizations and government entities.

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Suhler EB, Smith JR, Giles TR, et al. Infliximab therapy for refractory uveitis: 2-year results of a prospective trial. Arch Ophthalmol. 2009;127(6):819-822.

Sullivan TP, Welsh E,

Kerdel FA, et al.

Kirsner RS. Infliximab for hidradenitis suppurativa. Br J Dermatol. 2003;149(5):1046-1049.

Talley NJ, Abreu MT,

Achkar JP, et al.; American College of Gastroenterology IBD Task Force. An evidence-based systematic review on medical therapies for inflammatory bowel disease. Am J Gastroenterol. 2011;106(

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Terdiman JP,

Gruss CB,

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Turner D,

Otley AR, Mack D, et al. Development, validation, and evaluation of a pediatric ulcerative colitis activity index: a prospective multicenter study. Gastroenterology. 2007;133(2):423-432.

Turner D,

Ruemmele FM,

Orlanski-Meyer E, et al. Management of Pediatric Ulcerative Colitis, Part 1: Ambulatory Care-An Evidence-based Guideline From European Crohn's and Colitis Organization and European Society of

Paediatric Gastroenterology,

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Turner D,

Ruemmele FM,

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Paediatric Gastroenterology,

Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 2018;67(2):292-310.

Tynjala P,

Lindahl P,

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etanercept in the treatment of chronic uveitis associated with refractory juvenile idiopathic arthritis. Ann Rheum Dis. 2007;66(4):548-550.

Tynjälä P,

Vähäsalo P,

Tarkiainen M, et al. Aggressive combination drug therapy in very early

polyarticular juvenile idiopathic arthritis (ACUTE-JIA): a

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Topaloglu O, et al. Systematic review and meta-analysis: efficacy and safety of early biologic treatment in adult and

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Kooij SM, et al. Patient-reported outcomes in a randomized trial comparing four different treatment strategies in recent-onset rheumatoid arthritis. Arthritis Rheum. 2009;61:4-12.

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Coding

CPT Procedure Code Number(s)

N/A

ICD - 10 Procedure Code Number(s)

N/A

ICD - 10 Diagnosis Code Number(s)

See Attachment B.

HCPCS Level II Code Number(s)

J1745 Injection, infliximab, excludes biosimilar, 10 mg

Q5103 Injection, infliximab-dyyb, biosimilar, (inflectra), 10 mg

Q5104 Injection, infliximab-abda, biosimilar, (renflexis), 10 mg

Q5121 Injection, infliximab-axxq, biosimilar, (avsola), 10 mg

Revenue Code Number(s)

N/A

MPMiscCodesNarrativesPub
Modifiers

THE FOLLOWING MODIFIER IS USED WHEN REPORTING
Intravenous Infliximab and Related Biosimilars for Intravenous Use

JA - Administered Intravenously

Coding and Billing Requirements

For drugs that have more than one method of administration, application of the JA modifier is required to indicate the route of administration.

To report the intravenous route of administration, append the following modifier: JA Administered Intravenously

Cross Reference

Policy History

Revisions From MA08.019q:

01/01/2026

This version of the policy will become effective 01/01/2026.

The following HCPCS codes has been deleted from this policy:

Q5109 Injection, infliximab-qbtx, biosimilar, (ixifi), 10 mg

Revisions From MA08.019p:

10/01/2025

This version of the policy will become effective 10/01/2025.

The following ICD-10 CM codes have been added to this policy:

M05.A Abnormal rheumatoid factor and anti-citrullinated protein antibody with rheumatoid arthritis

Revisions From MA08.019o:

04/21/2025

This version of the policy will become effective 04/21/2025.

This policy has been updated to communicate the Company's coverage positions for Intravenous Infliximab and Related Biosimilars.

The criteria for immunotherapy-related toxicities has been updated, in alignment with National Comprehensive Cancer Network (NCCN) recommendations.

The following ICD-10 CM codes have been added to this policy as Medically Necessary:

D59.0 Drug-induced autoimmune hemolytic anemia
D59.2 Drug-induced nonautoimmune hemolytic anemia
K20.0 Eosinophilic esophagitis
K20.80 Other esophagitis without bleeding
K20.81 Other esophagitis with bleeding
K20.90 Esophagitis, unspecified without bleeding
K20.91 Esophagitis, unspecified with bleeding
K29.00 Acute gastritis without bleeding
K29.01 Acute gastritis with bleeding
K29.30 Chronic superficial gastritis without bleeding
K29.31 Chronic superficial gastritis with bleeding
K29.40 Chronic atrophic gastritis without bleeding
K29.41 Chronic atrophic gastritis with bleeding
K29.50 Unspecified chronic gastritis without bleeding
K29.51 Unspecified chronic gastritis with bleeding
K29.60 Other gastritis without bleeding
K29.61 Other gastritis with bleeding
K29.70 Gastritis, unspecified, without bleeding
K29.71 Gastritis, unspecified, with bleeding
K29.80 Duodenitis without bleeding
K29.81 Duodenitis with bleeding
K29.90 Gastroduodenitis, unspecified, without bleeding
K29.91 Gastroduodenitis, unspecified, with bleeding

Revisions From MA08.019n:

01/01/2025

This version of the policy will become effective 01/01/2025.

This policy has been updated to communicate the changes in the Company's preferred product designation. Non-preferred designation has been removed from this policy. There are no preferred products in this policy.

The following ICD-10 CM code has been added to this policy as Experimental/Investigational:

D89.84 IgG4-related disease

The following ICD-10 CM code has been removed from this policy:

D89.89 Other specified disorders involving the immune mechanism, not elsewhere

classified

Revisions From MA08.019m:

02/26/2024

This version of the policy will become effective 02/26/2024.

This policy has been updated to communicate the Company's coverage positions for Intravenous Infliximab and Related Biosimilars.

Ankylosing spondylitis indication has been expanded to include nonradiographic axial spondyloarthritis.

The criteria for acute graft-versus host disease and immunotherapy-related toxicities have been updated, in alignment with National Comprehensive Cancer Network (NCCN) recommendations.

A Billing Requirement was added to this policy regarding the Coding Modifier: JA Intravenous administration.

The following ICD-10 CM codes have been added to this policy as Medically Necessary:

I30.8 Other forms of acute pericarditis

J70.4 Drug-induced interstitial lung disorders, unspecified

M06.4 Inflammatory polyarthropathy

M45.A0 Non-radiographic axial spondyloarthritis of unspecified sites in spine

M45.A1 Non-radiographic axial spondyloarthritis of occipito-atlanto-axial region

M45.A2 Non-radiographic axial spondyloarthritis of cervical region

M45.A3 Non-radiographic axial spondyloarthritis of cervicothoracic region

M45.A4 Non-radiographic axial spondyloarthritis of thoracic region

M45.A5 Non-radiographic axial spondyloarthritis of thoracolumbar region

M45.A6 Non-radiographic axial spondyloarthritis of lumbar region

M45.A7 Non-radiographic axial spondyloarthritis of lumbosacral region

M45.A8 Non-radiographic axial spondyloarthritis of sacral and sacrococcygeal region

M45.AB Non-radiographic axial spondyloarthritis of multiple sites in spine

Revisions From MA08.019l:

01/01/2024	Effective 01/01/2024 this policy applies to New Jersey Medicare Advantage (MA) lines of business.
01/02/2023	This version of the policy will become effective 01/02/2023. This policy has been updated to communicate the Company's coverage positions for Intravenous Infliximab and Related Biosimilars. Sarcoidosis indication has been expanded to include types other than just pulmonary. The criteria for immunotherapy-related toxicities have been updated, in alignment with National Comprehensive Cancer Network (NCCN) recommendations. Granulomatosis with polyangiitis (Wegener’s granulomatosis) off-label indication has been removed from this policy due to paucity of evidence; other drugs are FDA-approved for this indication. The following ICD-10 CM codes have been added to this policy as Medically Necessary: D86.86 Sarcoid arthropathy D86.87 Sarcoid myositis D86.89 Sarcoidosis of other sites D86.9 Sarcoidosis, unspecified H44.111 Panuveitis, right eye H44.112 Panuveitis, left eye H44.113 Panuveitis, bilateral I40.9 Acute myocarditis, unspecified The following ICD-10 CM codes have been removed from this policy: M31.30 Wegener's granulomatosis without renal involvement M31.31 Wegener's granulomatosis with renal involvement The following ICD-10 CM codes have been removed from this policy, due to laterality/specificity of codes: H20.049, H44.139, M02.319, M02.329, M02.339, M02.349, M02.359, M02.369, M02.379, M05.019, M05.029, M05.039, M05.049, M05.059, M05.069, M05.079, M05.119, M05.129, M05.139, M05.149, M05.159, M05.169, M05.179, M05.219, M05.229, M05.239, M05.249, M05.259, M05.269, M05.279, M05.319, M05.329, M05.339, M05.349, M05.359, M05.369, M05.379, M05.419, M05.429, M05.439, M05.449, M05.459, M05.469, M05.479, M05.519, M05.529, M05.539, M05.549, M05.559, M05.569, M05.579, M05.619, M05.629, M05.639, M05.649, M05.659, M05.669, M06.679, M05.719, M05.729, M05.739, M05.749, M05.759, M05.769, M05.779, M05.819, M05.829, M05.839, M05.849, M05.859, M05.869, M05.879, M06.019, M06.029, M06.039, M06.049, M06.059, M06.069, M06.079, M06.819, M06.829, M06.839, M06.849, M06.859, M06.869, M06.879, M07.619, M07.629, M07.639, M07.649, M07.659, M07.669, M07.679

01/01/2024

Effective 01/01/2024 this policy applies to New Jersey Medicare Advantage (MA) lines of business.

01/02/2023

This version of the policy will become effective 01/02/2023.

This policy has been updated to communicate the Company's coverage positions for Intravenous Infliximab and Related Biosimilars.

Sarcoidosis indication has been expanded to include types other than just pulmonary.

The criteria for immunotherapy-related toxicities have been updated, in alignment with National Comprehensive Cancer Network (NCCN) recommendations.

Granulomatosis with polyangiitis (Wegener’s granulomatosis) off-label indication has been removed from this policy due to paucity of evidence; other drugs are FDA-approved for this indication.

The following ICD-10 CM codes have been added to this policy as Medically Necessary:

D86.86 Sarcoid arthropathy

D86.87 Sarcoid myositis

D86.89 Sarcoidosis of other sites

D86.9 Sarcoidosis, unspecified

H44.111 Panuveitis, right eye

H44.112 Panuveitis, left eye

H44.113 Panuveitis, bilateral

I40.9 Acute myocarditis, unspecified

The following ICD-10 CM codes have been removed from this policy:
M31.30 Wegener's granulomatosis without renal involvement

M31.31 Wegener's granulomatosis with renal involvement

The following ICD-10 CM codes have been removed from this policy, due to laterality/specificity of codes:
H20.049, H44.139,
M02.319, M02.329, M02.339, M02.349, M02.359, M02.369, M02.379,
M05.019, M05.029, M05.039, M05.049, M05.059, M05.069, M05.079,
M05.119, M05.129, M05.139, M05.149, M05.159, M05.169, M05.179,
M05.219, M05.229, M05.239, M05.249, M05.259, M05.269, M05.279,
M05.319, M05.329, M05.339, M05.349, M05.359, M05.369, M05.379,
M05.419, M05.429, M05.439, M05.449, M05.459, M05.469, M05.479,
M05.519, M05.529, M05.539, M05.549, M05.559, M05.569, M05.579,
M05.619, M05.629, M05.639, M05.649, M05.659, M05.669, M06.679,
M05.719, M05.729, M05.739, M05.749, M05.759, M05.769, M05.779,
M05.819, M05.829, M05.839, M05.849, M05.859, M05.869, M05.879,
M06.019, M06.029, M06.039, M06.049, M06.059, M06.069, M06.079,
M06.819, M06.829, M06.839, M06.849, M06.859, M06.869, M06.879,
M07.619, M07.629, M07.639, M07.649, M07.659, M07.669, M07.679

Revisions From MA08.019k:

10/01/2022

This version of the policy will become effective 10/01/2022.

The following ICD-10 code has been added to this policy:
I77.82 Antineutrophilic cytoplasmic antibody [ANCA] vasculitis

Revisions From MA08.019j:

03/21/2022

This version of the policy will become effective 03/21/2022.

Revisions From MA08.019i:

12/20/2021

This version of the policy will become effective 12/20/2021.

This policy has been updated to communicate the Company's coverage positions for the following indications, in alignment with peer-reviewed literature and National Comprehensive Cancer Network (NCCN):

Behcet's syndrome: Medically Necessary
Acute graft-versus-host disease (GVHD) in those who have undergone hematopoietic cell transplantation: Medically Necessary
IgG4-related disease: Experimental/Investigational

Revisions have been made to the following Medically Necessary indications:

Granulomatosis with polyangiitis (Wegener’s granulomatosis): rituximab has been added as an example of prior therapy
Inflammatory bowel disease arthritis: methotrexate has been added and cyclophosphamide has been removed, as examples of prior therapy
Reactive arthritis (Reiter's disease): azathioprine, cyclophosphamide, cyclosporine have been removed as examples of prior therapies
Crohn's disease, non-fistualizing: removed the timeframe of "at least 3 months" as a requirement of the prior therapies
Ulcerative colitis, adults: removed the timeframe of "at least 3 months" as a requirement of the prior therapies. Removed methotrexate as an example of prior therapy
Ulcerative colitis, children: aminosalicylates have been added as an example of prior therapies. Removed methotrexate as an example of prior therapy
Pyoderma gangrenosum: systemic corticosteroids, dapsone, DMARDs (e.g., cyclosporine) have been added as example a of prior therapy
Immunotherapy-related toxicity indications: updated indications and Dosing & Frequency, per National Comprehensive Cancer Network (NCCN)

The following ICD-10 CM codes have been added to this policy as Medically Necessary:

D89.810 Acute graft-versus-host disease

M35.2 Behcet's disease

The following ICD-10 CM code has been added to this policy as Experimental/Investigational:

D89.89 Other specified disorders involving the immune mechanism, not elsewhere classified

The following ICD-10 CM code has been removed from this policy:

M06.1 Adult-onset Still's disease

Revisions From MA08.019h:

10/01/2020

This policy has been identified for the ICD-10 CM code update, effective 10/01/2020.

The following ICD-10 CM codes have been added to this policy:

M05.7A Rheumatoid arthritis with rheumatoid factor of other specified site without organ or systems involvement

M05.8A Other rheumatoid arthritis with rheumatoid factor of other specified site

M06.0A Rheumatoid arthritis without rheumatoid factor, other specified site

M06.8A Other specified rheumatoid arthritis, other specified site

Revisions From MA08.019g:

07/01/2020

This policy has been identified for the HCPCS code update, effective 07/01/2020.

The following HCPCS code has been added to this policy to represent infliximab-axxq (Avsola™):
Q5121 Injection, infliximab-axxq, biosimilar, (avsola), 10 mg

Revisions From MA08.019f:

04/22/2019

This version of the policy will become effective 04/22/2019. The following indications have been added to this policy and Attachment A:

Medical Necessity criteria and dosing and frequency information for the coverage of toxicities related to immune checkpoint inhibitors: (Cardiac Toxicities, Diarrhea or Colitis, Elevated Serum Creatinine/Acute Renal Failure, Inflammatory Arthritis, Pneumonitis) in consideration of National Comprehensive Cancer Network-Clinical Practice Guidelines in Management of Immune Checkpoint Inhibitor-Related Toxicities.
Medical necessity criteria and dosing and frequency information for the coverage of Hidradenitis suppurativa.
High induction dosing and frequency information was added to Attachment A for moderate to severe pediatric ulcerative colitis and Crohn's disease.

Attachment B:
The following ICD-10 CM codes have been added to attachment B of this policy:
I30.0 Acute nonspecific idiopathic pericarditis
I40.8 Other acute myocarditis
I49.9 Cardiac arrhythmia, unspecified
J70.2 Acute drug-induced interstitial lung disorders
K52.1 Toxic gastroenteritis and colitis
L73.2 Hidradenitis suppurativa
N17.0 Acute kidney failure with tubular necrosis
N17.1 Acute kidney failure with acute cortical necrosis
N17.2 Acute kidney failure with medullary necrosis
N17.8 Other acute kidney failure
N17.9 Acute kidney failure, unspecified

The following statement was added to attachment B of this policy:

Report the most appropriate diagnosis code for toxicities related to immune checkpoint inhibitors.

Revisions From MA08.019e:

01/01/2019

This policy has been identified for the HCPCS code update, effective 01/01/2019.

The following HCPCS codes have been added to this policy:
Q5109 Injection, infliximab-qbtx, biosimilar, (ixifi), 10 mg

Revisions From MA08.019d:

04/01/2018

This policy has been identified for the HCPCS code update, effective 04/01/2018.

The following HCPCS code has been deleted from this policy:
Q5102 Injection, infliximab, biosimilar, 10 mg

The following HCPCS codes have been added to this policy:
Q5103 Injection, infliximab-dyyb, biosimilar, (inflectra), 10 mg
Q5104 Injection, infliximab-abda, biosimilar, (renflexis), 10 mg

Revisions From MA08.019c:

12/27/2017

This Policy has undergone a routine review, and the medical necessity criteria have been revised as follows:

New Biosimilars: infliximab-abda (Renflexis™) and infliximab-qbtx (Ixifi™)
Medical Necessity criteria and Dosing and Frequency Information for the coverage of non-infectious uveitis
Minor updates to the following indications due to updates to Standards of Care.
- Inflammatory bowel disease arthritis
- Psoriatic arthritis
- Rheumatoid arthritis (RA)
- Crohn's disease: non-fistualizing
- Plaque psoriasis

Revisions From MA08.019b:

03/08/2017

This policy was updated to reflect the indications for the newly FDA-approved biosimilar, infliximab-dyyb (Inflectra).

The following ICD-10 codes have been removed from this policy, since other codes are more appropriate:
K60.3, K60.4, K60.5, K63.2, M01.x11, M01.x12, M01.x21, M01.x22, M01.x31, M01.x32, M01.x41, M01.x42, M01.x51, M01.x52 M01.x61, M01.x62, M01.x71, M01.x72, M01.x8, M01.x9, M06.211, M06.212, M06.221, M06.222, M06.231, M06.232, M06.241, M06.242, M06.251, M06.252, M06.261, M06.262, M06.271, M06.272, M06.28, M06.29, M06.311, M06.312, M06.321, M06.322, M06.331, M06.332, M06.341, M06.342, M06.351, M06.352, M06.361, M06.362, M06.371, M06.372, M06.38, M06.39, M06.4, M08.011, M08.012, M08.021, M08.022, M08.031, M08.032, M08.041, M08.042, M08.051, M08.052, M08.061, M08.062, M08.071, M08.072, M08.08, M08.211, M08.212, M08.221, M08.222, M08.231, M08.232, M08.241, M08.242, M08.251, M08.252, M08.261, M08.262, M08.271, M08.272, M08.28, M08.29, M08.811, M08.812, M08.821, M08.822, M08.831, M08.832, M08.841, M08.842, M08.851, M08.852, M08.861, M08.862, M08.871, M08.872, M08.88, M08.89, M08.911, M08.912, M08.921, M08.922, M08.931, M08.932, M08.941, M08.942, M08.951, M08.952, M08.961, M08.962, M08.971, M08.972, M08.98, M36.8, M48.8x1, M48.8x2, M48.8x3, M48.8x4, M48.8x5, M48.8x6, M48.8x7, M48.8x8, N82.0, N82.2, N82.3, N82.4, N82.8.

Revisions From MA08.019a:

01/01/2017

This policy has been identified for the HCPCS code update, effective 01/01/2017.
The following HCPCS narrative has been revised in this policy:

FROM: J1745 Injection, infliximab, 10 mg
TO: J1745 Injection, infliximab, excludes biosimilar, 10 mg

Revisions From MA08.019:

12/09/2015	This version of the policy will become effective 12/09/2015. The policy has been reviewed and reissued to communicate the Company’s continuing position on infliximab (Remicade®).
01/01/2015	This is a new policy.

Version Effective Date:

1/1/2026

Version Issued Date:

1/2/2026

Version Reissued Date:

Medicare Advantage

Medical Policy

Notification

Policy

Guidelines

Description

References

Coding

CPT Procedure Code Number(s)

ICD - 10 Procedure Code Number(s)

ICD - 10 Diagnosis Code Number(s)

HCPCS Level II Code Number(s)

Revenue Code Number(s)

MPMiscCodesNarrativesPub​Modifiers

Coding and Billing Requirements

Cross Reference

Policy History

MPMiscCodesNarrativesPub
Modifiers