LCD L35677

Coverage Guidance

Title XVIII of the Social Security Act 1862(a)(1)(A) allows coverage and payment for only those services that are considered to be medically reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member.

CMS Internet-Only Manual, Pub. 100-02, Medicare Benefit Policy Manual, Chapter 1, §30 Drugs and Biologicals, §30.1 Drugs Included in the Drug Compendia, §30.2 Approval by Pharmacy and Drug Therapeutics Committee, §30.3 Combination Drugs, §30.4 Drugs Specially Ordered for Inpatients, §30.5 Drugs for Use Outside the Hospital

CMS Internet-Only Manual, Pub. 100-02, Medicare Benefit Policy Manual, Chapter 15, §50 Drugs and Biologicals, §50.1 Definition of Drug or Biological, §50.4.1 Approved Use of Drug, §50.4.2 Unlabeled Use of Drug, §50.4.3 Examples of Not Reasonable and Necessary, §50.4.5 Off-Label Use of Drugs and Biologicals in an Anti-Cancer Chemotherapeutic Regimen

Indications and Limitations of Coverage

Infliximab is a chimeric monoclonal antibody that binds specifically to tumor necrosis factor alpha (TNFa) and blocks its activity. Overproduction of TNFa, which is a key inflammatory mediator, leads to inflammation in conditions such as Crohn’s disease, rheumatoid arthritis and other autoimmune diseases.

The use of infliximab will be considered medically reasonable and necessary in the following circumstances:

• To reduce the signs and symptoms and induce and maintain clinical remission in adult and pediatric patients with moderately to severely active Crohn’s disease in patients who have had an inadequate response to conventional therapy (e.g., corticosteroids, aminosalicylates, and immunosuppressive agents).

• To reduce the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure for patients with fistulizing Crohn’s disease. Normally, the patient receives an infusion for this indication at weeks 0, 2 & 6. Subsequent treatments will be covered if the patient responds to the initial treatment as demonstrated by a reduction in signs and symptoms.

• To reduce the signs and symptoms of active arthritis, inhibiting the progression of structural damage and improving physical function, in patients with psoriatic arthritis. Normally, the patient receives an infusion for this indication at weeks 0, 2 & 6. Subsequent treatments will be covered if the patient responds to the initial treatment as demonstrated by a reduction in signs and symptoms.

• When used in combination with methotrexate, to reduce the signs and symptoms, inhibit the progression of structural damage and improve physical function in patients with moderately to severely active rheumatoid arthritis. Normally, the patient receives an infusion of infliximab for this indication at weeks 0, 2 & 6 and then approximately every 8 weeks.

• To reduce the signs and symptoms in patients with active ankylosing spondylitis. Normally the patient receives an infusion for this indication at 0, 2 & 6 weeks. Subsequent treatment will be covered if the patient responds to the initial treatment as demonstrated by a reduction in signs and symptoms.

• For the treatment of adult patients with chronic severe plaque psoriasis (as evidenced by plaques covering at least 10% of the body surface) who have failed prior treatment with psoralen-ultraviolet A (UVA), or ultraviolet B (UVB) light therapy; or are candidates for systemic therapy when other conventional systemic therapies have failed (methotrexate, cyclosporine, Soriatane®); or the patient has contraindications to these treatments. Infliximab should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician. Normally the patient receives an infusion at 0, 2 & 6 weeks and every 8 weeks thereafter.

• To reduce signs and symptoms, achieve clinical remission and mucosal healing, and eliminate corticosteroid use in patients with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy, such as aminosalicylates, corticosteroids, or immunosuppressants (unless the patient is unable to tolerate these drugs). Normally, the patient receives an infusion for this indication at 0, 2 & 6 weeks, and then every 8 weeks thereafter.

• As an off-label use for reactive arthritis and inflammatory bowel disease (e.g., Reiter’s Syndrome who have failed or are intolerant to non-steroidal anti-inflammatory drugs (NSAIDs), methotrexate and sulfasalazine).

• As an off-label use for hidradenitis suppurativa in the treatment of persons with severe disease refractory to systemic antibiotics and surgical treatments.

• As an off-label use for Behçet’s Disease (BD), also known as Behçet’s Syndrome, in patients without an adequate response to initial therapy, for the treatment of clinical manifestations of BD such as severe ocular involvement, major organ involvement, severe gastrointestinal or neurological involvement and resistant cases of joint or mucocutaneous involvement (i.e., painful oral and genital ulcers).

• As an off-label use for patients with chronic pulmonary sarcoidosis who remain symptomatic despite treatment for 3 or more months with steroids (10 mg per day or more) and immunosuppressants (such as azathioprine, cyclophosphamide or methotrexate) or have a contraindication or intolerance to 1 immunosuppressant (such as azathioprine, cyclophosphamide, or methotrexate) and the patient is not receiving infliximab in combination with either of the following: 1) Biologic disease-modifying anti-rheumatic drugs (DMARDs) [e.g., Enbrel® (etanercept), Humira® (adalimumab), Cimzia® (certolizumab), Simponi® (golimumab)] 2) Janus kinase inhibitor [e.g., Xeljanz® (tofacitinib)]. The current and prospective roles of infliximab in the treatment of pulmonary sarcoidosis do not currently have Food and Drug Administration (FDA) approval; therefore, it is recommended that providers consult the literature for proper dosing of infliximab.

Note: For patients, who are unable to tolerate methotrexate or in the rare instance that methotrexate is contraindicated for a patient, treatment with infliximab alone will be covered only if documentation is maintained in the patient’s record that clearly indicates the reason that the patient cannot take methotrexate.

Infliximab will only be covered for the above indications when no contraindications to its use exist including:

a. Class III or IV congestive heart failure; or

b. Untreated active or latent tuberculosis

LIMITATIONS

When used in combination with other biologics, such as Enbrel®(etanercept), Kineret® (anakinra), Orencia®(abatacept), Rituxan®(rituximab), Humira®(adalimumab), Cimzia® (certolizumab), Simponi® (golimumab), or a Janus kinase inhibitor [e.g. Xeljanz® (tofacitinib)], infliximab is considered not medically reasonable and necessary and therefore, not covered.

Summary of Evidence

N/A

Analysis of Evidence

N/A

Associated Information

Documentation Requirements

Medical record documentation that is maintained by the performing physician must substantiate the medical necessity for the use of infliximab by clearly indicating the relevant clinical signs and symptoms related to the medical condition for which this drug is indicated. The documentation must also include all prior treatment regimens and the patient’s response to that therapy.

For fistulizing Crohn’s disease, episodic retreatment will be covered if the medical record substantiates that the patient had a reduction in the clinical signs and symptoms of the disease after the initial treatment.

For hidradenitis suppurativa, documentation should include: a listing of other differential diagnoses that have been ruled out and the history of failed antibiotic treatment, prior to the inception of infliximab treatment.

For rheumatoid arthritis, the medical record must clearly indicate:

• the patient is receiving infliximab in combination with methotrexate; or

• the patient is intolerant of methotrexate; or

• the patient has a medical condition that contraindicates the use of methotrexate.

For maintenance therapy, submit documentation of the start date for infliximab, the current status of the patient, their current response to therapy and current dosage.

Documentation must be legible, relevant and sufficient to justify the services billed. This documentation must be made available to the A/B MAC upon request.

Utilization Guidelines

It is expected that these services would be performed as indicated by current medical literature and/or standards of practice. When services are performed in excess of established parameters, they may be subject to review for medical necessity.

Bibliography

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