Coverage Policies

Effective Date:

a)    This policy will apply to all services performed on or after the above revision date which will become the new effective date.

b)    For all services referred to in this policy that were performed before the revision date, contact customer service for the rules that would apply.

1)    Remicade requires prior authorization. For new patient starts, a biosimilar product must be tried first before Remicade would be approved.  All Remicade renewal/continuation requests also require documentation of trial of a covered biosimilar (Inflectra or Renflexis).  If trial of a covered biosimilar product is not considered to be suitable for the member, then the provider needs to submit a clinical rationale with relevant clinical literature.

2)    Infliximab is covered for the following diseases:

a)    Rheumatoid arthritis,

b)    Psoriatic arthritis,

c)    Crohn’s disease/ Ulcerative colitis

d)    Ankylosing spondylitis,

e)    Psoriasis,

f)     Posterior uveitis associated with Behcet’s syndrome

3)    Covered infliximab biosimilars are subject to retrospective review to ensure compliance with the Medical Policy Statement below.

Infliximab biosimilar products (Inflectra or Renflexis) are covered without prior authorization (PA) but are subject to retrospective review to ensure compliance with the Medical Policy Statement below. Remicade requires prior authorization (PA). For new patient starts, a covered biosimilar product (Inflectra or Renflexis) must be tried first before Remicade would be approved.  All Remicade renewal/continuation requests also require documentation of trial of a covered biosimilar.  If trial of a covered biosimilar product is not considered to be suitable for the member, then the provider needs to submit a clinical rationale with relevant clinical literature.

1)    Rheumatoid Arthritis, Psoriatic Arthritis

A)   Members age 18 and older with active disease who has failed to respond to any of the non-steroidal anti-inflammatory drugs (NSAIDS).

B)   The recommended dose is 3 mg/kg as an infusion at 2 and 6 weeks after the initial infusion, then every 8 weeks. For continued use beyond 30 weeks, there must be documentation of demonstrable improvement.

C)   In cases of incomplete response or relapse, consideration may be given to increasing the dose as high as 10 mg/kg per dose, or increasing the dosing frequency to every 4 weeks.

2)    Crohn’s Disease

A)   Continuation of therapy after the initial 6-month period should be based on patient response to therapy. Indicated for the treatment of moderately to severely active Crohn’s Disease or fistulizing Crohn’s Disease in patients age 6 years and older who have had an inadequate response to conventional therapy:

·         Corticosteroids

·         5-aminosalicylates, and/or

·         Mercaptopurine (Purinethol) with azathioprine (Imuran). 

B)   The recommended dosing is a loading schedule of 5 mg/kg doses given at weeks 0, 2, and 6. Therapy then continues at 5 mg/kg every 8 weeks. Continuation of therapy after the initial 3 doses should be based on patient response to therapy.

C)   If there is no response to therapy by week 14, no response is likely and the treatment should be discontinued.

D)   For patients who respond initially but relapse while on treatment, consideration may be given to increasing the dose to 10 mg/kg every 8 weeks.

3)    Ankylosing Spondylitis

A)   Member is 18 years of age or older;

B)   The initial dosing is a loading regimen of 5 mg/kg per dose at weeks 0, 2, and 6;

C)   Maintenance dosing is 5 mg/kg per dose every 6 weeks;

D)   Continuation of therapy after the initial 3 months should be based on patient’s response to therapy.

4)    Psoriasis

Member is 18 years of age or older, has moderate to severe chronic plaque psoriasis, and meets the following selection criteria:

A)   Plaque psoriasis has been present for more than 1 year; AND

B)   Ten percent or more body surface area is affected by plaque psoriasis; AND

C)   Member has a history of failure for at least a 3 month trial of, contraindication, or intolerance to ALL of the following:

                            i.    Topical therapy with corticosteroids, Vitamin D analogs (e.g. calcitriol, calcipotriene), calcineurin inhibitor (e.g. tacrolimus, pimecrolimus), or salicylic acid combination product; AND

                          ii.    Phototherapy of at least 3 months duration with narrow-band UVB (in the office or at home) used alone or in combination with topical or systemic therapy (see BI029 for additional information regarding UV light therapy).   This requirement may be waived in any of the following situations:

1.    History or presence of melanoma or other skin cancer, lupus erythematosus, or xeroderma pigmentosum,

2.    Psoriasis involving areas around the eye where eye protection may cause blockage of phototherapy to affected area,

3.    Documented systemic disease involving the joints (meeting specific criteria for psoriatic arthritis), OR

4.    Very sever plaque thickness or scaling (4 on a scale of 0 to 4); AND

                         iii.    Systemic therapy of at least 3 months duration with methotrexate or other non-biologic DMARD. This requirement may be waived in any of the following situations:

1.    Member has chronic hepatic disease,

2.    Member has acquired immunodeficiency disease (AIDS),

3.    Member is pregnant or breast-feeding, OR

4.    Member has anemia, neutropenia, or thrombocytopenia; AND

                         iv.    History of inadequate response to Humira.

5)    Ulcerative Colitis

Members 6 years of age or older with moderate to severe active ulcerative colitis refractory to one or more of the following standard therapies:

A)   Corticosteroids (e.g., Prednisone, Methylprednisolone);

B)   5-aminosalicylic acid agents (e.g., Sulfasalazine, Mesalamine, Balsalazide);

C)   Immunosuppressant’s (e.g., azathioprine, cyclosporine, 6-mercaptopurine).

6)    Posterior Uveitis Associated With Behcet’s Syndrome

Members with refractory posterior uveitis associated with Behcet’s syndrome that has had an inadequate response to conventional therapy with systemic corticosteroids and/or immunosuppressive agents. Continued use of Remicade after six months should only be considered in the case of objectively documented improvement (improvement in visual acuity or reduction in number of episodes).

Codes Used In This BI:

J1745 – Infliximab Injection, 10 mg

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

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

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

84999 – Unlisted chemistry procedure (used for infliximab antibodies)

The use of Anser IFX to test for infliximab antibodies is considered experimental and investigational and is not covered.

Infliximab is a chimeric monoclonal antibody which has FDA approval for use in combination with methotrexate in the treatment of patients with rheumatoid arthritis who have had an inadequate response to methotrexate and for the treatment of severe Crohn’s disease for patients who have failed to respond to prior conventional therapy.

Rheumatoid Arthritis: Infliximab, in combination with methotrexate, is indicated for reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to methotrexate. Infliximab works by neutralizing the biological activity of a substance called tumor necrosis factor alpha (TNF-alpha), which is an important cause of the inflammatory processes of rheumatoid arthritis. Because Infliximab neutralizes the TNF-alpha, patients experience improvement in their joints for sustained periods of time.

Crohn’s Disease: Infliximab helps reduce signs and symptoms and induce and maintain clinical remission in patients with moderately to severely active Crohn`s disease who have had an inadequate response to conventional therapy. Infliximab is also indicated for the reductions in the number of draining enter cutaneous fistulae in patients with fistulizing Crohn`s disease. The safety and efficacy of therapy for fistulizing Crohn`s disease continued beyond 3 doses have not been established.

Psoriasis:  The U.S. Pharmacopeial Convention (2003) has concluded that psoriatic arthritis and psoriasis are accepted indications for infliximab. A controlled clinical study (Chaudhari, et al., 2001) has demonstrated the short-term effectiveness of infliximab in plaque psoriasis. In a controlled clinical trial in which patients and investigators were blinded for the first 10 weeks, participants were assigned to either of two doses of infliximab (5 mg/kg or 10 mg/kg at baseline, 2 weeks, and 6 weeks) or to placebo. Nineteen of 22 patients assigned to infliximab achieved good or better physician`s overall assessments, compared with two of 11 patients assigned to placebo. In initial studies, remissions seemed to be durable, with many patients improving for six months or longer.

Ulcerative Colitis: Conventional treatment options for patients with severe corticosteroid-refractory ulcerative colitis include intravenous cyclosporine, which is frequently limited by toxicity, or colectomy. Studies have shown that infliximab, improves clinical, endoscopic, and histologic outcomes in patients with severely active ulcerative colitis refractory to conventional therapy, allowing corticosteroid sparing and reducing the need for colectomy. Two Phase III randomized, placebo-controlled clinical trials have demonstrated efficacy of infliximab in inducing and maintaining clinical response and remission of refractory moderate to severe ulcerative colitis (Rutgeerts, et al., 2005; Sandborn, et al., 2005)

Safety Considerations:

1.    Congestive heart failure: doses above 5 mg/kg should not be used in patients with congestive heart failure.

2.    There have been reports of fatal exacerbations of rheumatoid arthritis associated fibosing alveolitis in patients given infliximab.

3.    Infections: severe infections have occurred in patients under treatment with infliximab. This should not be unexpected in a treatment that suppresses immune function.

4.    Late development of malignancy: data to date do not give a clear picture of whether late malignancy is or is not a risk of chronic infliximab treatment. It is likely it will take years for us to find out.

5.    Liver disease: liver toxicity has been observed, including acute liver failure, jaundice, hepatitis, and cholestasis. These are rare but potentially catastrophic occurrences, some of which have been fatal or required liver transplant surgery.

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2. Arkansas BlueCross BlueShield Coverage Policy Manual; infliximab (Remicade) at: www.arkbluecross.com.
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This policy applies to all health plans administered by QualChoice, both those insured by QualChoice and those that are self-funded by the sponsoring employer, unless there is indication in this policy otherwise or a stated exclusion in your medical plan booklet.  Consult the individual plan sponsor Summary Plan Description (SPD) for self-insured plans or the specific Evidence of Coverage (EOC) for those plans insured by QualChoice.  In the event of a discrepancy between this policy and a self-insured customer’s SPD or the specific QualChoice EOC, the SPD or EOC, as applicable, will prevail.  State and federal mandates will be followed as they apply.