Rituximab (Rituxan®) is a genetically engineered chimeric murine/human monoclonal antibody. It binds specifically to the antigen CD20 (human B-lymphocyte-restricted differentiation antigen, Bp35). This antigen is a hydrophobic transmembrane protein that is located on pre-B and mature B lymphocytes. It is also expressed on more than 90 percent of B-cell non-Hodgkin's lymphomas, but it is not expressed on hematopoietic stem cells, pro-B cells, normal plasma cells, or other normal tissues.

Rituximab and hyaluronidase human (Rituxan Hycela™) is a combination of rituximab and hyaluronidase human in a subcutaneous formulation that is given by a healthcare professional after an initial administration of intravenous rituximab (Rituxan). These two products are different formulations and cannot be used interchangeably.

Rituximab-abbs (Truxima®), rituximab-arrx (Riabni™), and rituximab-pvvr (Ruxience™) are biosimilars of rituximab (Rituxan).

Preferred Products

Rituximab-arrx (Riabni) and rituximab-pvvr (Ruxience) are the preferred rituximab biosimilars for individuals initiating new therapy for oncologic indications when the clinical criteria within this policy are met. A non-preferred product will be considered when the individual has a documented therapy failure after an adequate therapeutic trial of a preferred product, or the preferred product has not been tolerated or is contraindicated.

Rituximab-arrx (Riabni) and rituximab-pvvr (Ruxience) are the preferred rituximab biosimilars for Rheumatoid Arthritis (RA) indications when the clinical criteria within this policy are met. A non-preferred product will be considered when the individual has a documented therapy failure after an adequate therapeutic trial of a preferred product, or the preferred product has not been tolerated or is contraindicated.

Adequate therapeutic trial is defined as 180 days from first dose of therapy at Food and Drug Administration (FDA) or compendia based therapeutic doses of preferred product.

New therapy is defined as no previous utilization within the last 180 calendar days.

Rituximab (Rituxan)

Rituximab (Rituxan) may be considered medically necessary for ANY of the following indications:

Antineutrophil Cytoplasmic Antibody‒Associated Vasculitides (Granulomatosis with Polyangiitis [Wegener Granulomatosis] and Microscopic Polyangiitis)

• Treatment of individuals with antineutrophil cytoplasmic antibody‒associated vasculitides (i.e., granulomatosis with polyangiitis (GPA) [Wegener granulomatosis] and microscopic polyangiitis), in combination with glucocorticoids; or

Chronic Lymphocytic Leukemia (CLL)

• Treatment of previously untreated and previously treated CD20-positive CLL in combination with fludarabine and cyclophosphamide (FC); or

Non-Hodgkin’s Lymphoma (NHL)

Treatment of NHL in any of the following:

• Relapsed or refractory, low grade or follicular, CD20-positive B-cell NHL as a single agent; or
• Previously untreated follicular, CD20-positive, B-cell NHL in combination with first line chemotherapy and, in individuals achieving a complete or partial response to rituximab (Rituxan) in combination with chemotherapy, as single-agent maintenance therapy; or
• Non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL as a single agent after first-line cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy; or
• Previously untreated diffuse large B-cell, CD20-positive NHL in combination with (cyclophosphamide, doxorubicin, vincristine, and prednisone) (CHOP) or other anthracycline-based chemotherapy regimens; or

Pemphigus Vulgaris (PV)

• Treatment of moderate to severe treatment-refractory PV in individuals 18 years or older; or

Rheumatoid Arthritis (RA)

• Treatment of individuals 18 years of age or older with RA who meet the following criteria:
  • RA is moderately to severely active (e.g., greater than or equal to eight (8) swollen and tender joints); and
  • Rituximab (Rituxan) is administered in combination with methotrexate, or other conventional synthetic disease-modifying anti-rheumatic drug (DMARD) if methotrexate is contraindicated; and
    • Individual has had an inadequate response to one (1) or more tumor necrosis factor inhibitors, or is not suitable for treatment with tumor necrosis factor inhibitors; or
    • Combination therapy with methotrexate or other conventional synthetic DMARD not applicable to individuals who have had an inadequate response to methotrexate or other conventional synthetic DMARDs.

Compendia Sources
Rituximab (Rituxan) may be considered medically necessary for treatment of any of the current category 1, 2A, or 2B NCCN recommendations

Reauthorization Criteria for rituximab (Rituxan)

Continuation of therapy with rituximab (Rituxan) for non-oncologic indications may be considered medically necessary when the following criteria is met: 

• The individual has one of the above diagnoses; and
• For RA only; the individual has had an adequate therapeutic trial and experienced a documented drug therapy failure or intolerance to the preferred product; and
• Provider attestation that individual has demonstrated a disease stability or beneficial response to therapy; and
• Reauthorization valid for 12 months.

The use of rituximab (Rituxan) for all other indications not listed on this policy is considered experimental/investigational and therefore, not covered. Scientific evidence does not support the use for all other indications.

Other clinically supported indications

Rituximab (Rituxan) may be considered medically necessary for ANY of the following 2b or higher off-label indications:

Autoimmune Hemolytic Anemia (AIHA)

• Warm AIHA in glucocorticoid-refractory or glucocorticoid-dependent individuals; or
• Cold agglutination syndrome; or

Churg-Strauss Syndrome (Eosinophilic Granulomatosis with Polyangiitis)

• First-line treatment in combination with glucocorticoids for individuals with severe (organ-threatening) disease; or
• Add-on therapy for treatment-refractory disease; or

Epstein-Barr virus disease; Prophylaxis - Hemopoietic stem cell transplant

• Prophylaxis for Epstein Barr virus infection in pediatric individuals undergoing hematopoietic stem cell transplant; or

Evans syndrome (Pediatric only)

• Treatment for Evans syndrome refractory to immunosuppressive therapy; or

Hemophilia

• Treatment of individuals 18 years of age or older for hemophilia with acquired inhibitors in individuals who are refractory to conventional first line treatments (i.e. immunosuppression with prednisone and cyclophosphamide); or

Hepatitis C Virus‒Associated Cryoglobulinemic Vasculitis

• As add-on therapy for individuals with hepatitis C virus‒associated cryoglobulinemic vasculitis who have:
  • Active disease resistant to antiviral drugs; or
  • Severe or life-threatening cryoglobulinemic vasculitis; or

Idiopathic Membranous Nephropathy

• As treatment for idiopathic membranous nephropathy; or

Immune thrombocytopenia, previously treated (Pediatric only)

• Treatment for pediatric individuals with previously treated primary and secondary immune thrombocytopenia; or

Inflammatory Myopathy (Idiopathic)

• Treatment for individuals 18 years of age or older who have failed to respond to, or are intolerant to, another immunosuppressant (e.g. methotrexate) with refractory idiopathic inflammatory myopathy; or

Lupus Nephritis

• As add-on therapy for lupus nephritis refractory to standard first-line treatment regimen; or

Microscopic polyarteritis nodosa (Adult only)

• treatment for microscopic polyarteritis nodosa in combination with glucocorticoids; or

Minimal change disease (Pediatric only)

• Treatment for remission induction and maintenance of remission in pediatric individuals who have refractory, steroid-dependent or steroid-resistant minimal change disease; or

Multiple Sclerosis (Primary Progressive)

• Treatment for individuals 18 years of age or older with primary progressive multiple sclerosis who have gadolinium brain lesions at baseline and have failed treatment with ocrelizumab; or

Multiple Sclerosis (Relapsing Remitting)

• Treatment of relapsing remitting multiple sclerosis when the individuals has experienced therapeutic failure, intolerance, or contraindication to two (2) alternative drug therapies indicated for the treatment of multiple sclerosis (e.g. Avonex, Aubagio, Gilenya, etc.); or   

Myasthenia Gravis

• Treatment for individuals 18 years of age or older with myasthenia gravis refractory to conventional therapy (e.g., azathioprine, corticosteroids, immunosuppressants, plasma exchange, IV immunoglobulin, thymectomy); or

Myopathy, Idiopathic Inflammatory

• Treatment for refractory idiopathic inflammatory myopathy in individuals who have failed to respond to, or are intolerant to, another immunosuppressant (e.g. methotrexate); or

Neuromyelitis Optica

• Rituximab (Rituxan) may be considered medically necessary as treatment for neuromyelitis optica for relapse prevention; or

Pemphigoid Diseases

• Treatment for ANY of the following pemphigoid diseases in treatment-refractory individuals:
  • Bullous pemphigoid; or
  • Mucous membrane pemphigoid, including ocular cicatricial pemphigoid; or
  • Epidermolysis bullosa acquisita; or

Pemphigus Diseases

• Treatment for pemphigus diseases (i.e., pemphigus vulgaris, paraneoplastic pemphigus); or

Pemphigus Foliaceus

• Treatment for individuals 18 years of age or older with pemphigus foliaceus in combination with a tapering course of corticosteroids; or

Sjögren’s Syndrome (Primary)

• Treatment for individuals 18 years of age or older with primary Sjögren’s syndrome as a one (1) time course of treatment over 15 days; or

Systemic Lupus Erythematosus

• Treatment as add-on therapy for systemic lupus erythematosus refractory to immunosuppressive therapy; or

Systemic Sclerosis (Scleroderma)

• Treatment for systemic sclerosis (scleroderma) in individuals refractory to first-line treatment; or

Thrombocytopenic purpura (Idiopathic)

• Treatment for individuals 18 years of age or older with idiopathic thrombocytopenic purpura refractory to first-line therapy (e.g., corticosteroids, IV immune globulin, splenectomy, etc.) who are at risk of bleeding (grade 2C); or

Thrombotic Thrombocytopenic Purpura

• Treatment in combination with steroids and plasma exchange in individuals 18 years of age or older with refractory thrombotic thrombocytopenic purpura (i.e., lack of response to plasma exchange therapy and glucocorticoids).

Reauthorization Criteria for rituximab (Rituxan)

Continuation of therapy with rituximab (Rituxan) for non-oncologic indications may be considered medically necessary when the following criteria is met:

• The individual has one of the above diagnoses; and
• For RA only; the individual has had an adequate therapeutic trial and experienced a documented drug therapy failure or intolerance to the preferred product; and
• Provider attestation that individual has demonstrated a disease stability or beneficial response to therapy; and
• Reauthorization valid for 12 months.

The use of rituximab for all other indications not listed on this policy is considered experimental/investigational and therefore, not covered. Scientific evidence does not support the use for all other indications.

Rituximab and hyaluronidase human (Rituxan Hycela^®) subcutaneous (SC) – healthcare administered

Rituximab and hyaluronidase human (Rituxan Hycela) may be considered medically necessary for adult individuals 18 years of age and older only after individual has received at least one full dose of a rituximab product by intravenous infusion for ANY of the following indications:

Chronic lymphoid leukemia (CLL)

• Previously untreated and previously treated CLL in combination with fludarabine and cyclophosphamide (FC); or

Diffuse Large B-Cell Lymphoma (DLBCL)

• Previously untreated DLBCL in combination with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or other anthracycline-based chemotherapy regimens; or

Follicular lymphoma (FL)

• Relapsed or refractory, follicular lymphoma as a single agent; or
• Previously untreated follicular lymphoma in combination with first line chemotherapy and, in individuals achieving a complete or partial response to rituximab (Rituxan) in combination with chemotherapy, as single-agent maintenance therapy; or
• Non-progressing (including stable disease), follicular lymphoma as a single agent after first-line cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy; or

Compendia Sources
Rituximab and hyaluronidase human (Rituxan Hycela^®) may be considered medically necessary for treatment of any of the current category 1, 2A, or 2B NCCN recommendations

Individuals receiving rituximab and hyaluronidase human (Rituxan Hycela) cannot have a live vaccination prior to or during treatment with rituximab and hyaluronidase human (Rituxan Hycela).

The use of rituximab and hyaluronidase human (Rituxan Hycela) for all other indications not listed on this policy is considered experimental/investigational and therefore, not covered. Scientific evidence does not support the use for all other indications.

Rituximab-abbs (Truxima) or rituximab-pvvr (Ruxience) may be considered medically necessary for the treatment of individuals 18 years and older for ANY of the following indications: 

Chronic Lymphocytic Leukemia (CLL)

• For previously untreated or previously treated CD20-positive CLL in combination with fludarabine and cyclophosphamide; or

Granulomatosis with Polyangitis, Wegener’s Granulomatosis, and Microscopic Polyangiitis

• As therapy in combination with glucocorticoids; or

Non-Hodgkin’s Lymphoma (NHL)

• Relapsed or refractory, low grade or follicular, CD20-positive B-cell NHL as a single agent; or
• Previously untreated follicular, CD20-positive, B-cell NHL in combination with first line chemotherapy and, in individuals achieving a complete or partial response to a rituximab product in combination with chemotherapy, as a single agent maintenance therapy; or
• Non-progressive (including stable disease), low-grade, CD20-positive, B-cell NHL as a single agent after first-line cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy; or
• Previously untreated DLBCL, CD20-positive NHL in combination with CHOP or anthracycline-based chemotherapy regimens; or

Rheumatoid Arthritis (RA)

• As therapy in combination with methotrexate, or other conventional synthetic DMARD if methotrexate is contraindicated, for moderately-to-severely-active RA who have had an inadequate response to one or more TNF antagonist therapies:
  • Combination therapy with methotrexate or other conventional synthetic DMARD not applicable to individuals who have had an inadequate response to methotrexate or other conventional synthetic DMARDs

Compendia Sources

Rituximab-abbs (Truxima) or rituximab-pvvr (Ruxience) may be considered medically necessary for treatment of any of the current category 1, 2A, or 2B NCCN recommendations.

Reauthorization Criteria for Rituximab-abbs (Truxima) or Rituximab-pvvr (Ruxience)

Continuation of therapy with rituximab-abbs (Truxima) or rituximab-pvvr (Ruxience) for non-oncologic indications may be considered medically necessary when the following criteria is met:

• The individual has one of the above diagnoses; and
• For RA only; individual has had an adequate therapeutic trial and experienced a documented drug therapy failure or intolerance to the preferred product; and
• Provider attestation that individual has demonstrated a disease stability or beneficial response to therapy; and
• Reauthorization valid for 12 months.

The use of rituximab-abbs (Truxima) or rituximab-pvvr (Ruxience) for all other indications not listed on this policy is considered experimental/investigational and therefore, not covered. Scientific evidence does not support the use for all other indications. 

Rituximab-arrx (Riabni) may be considered medically necessary for the treatment of individuals 18 years and older for ANY of the following indications: 

Chronic Lymphocytic Leukemia (CLL)

• For previously untreated or previously treated CD20-positive CLL in combination with fludarabine and cyclophosphamide; or

Granulomatosis with Polyangitis, Wegener’s Granulomatosis, and Microscopic Polyangiitis

• As therapy in combination with glucocorticoids; or

Non-Hodgkin’s Lymphoma (NHL)

• Relapsed or refractory, low grade or follicular, CD20-positive B-cell NHL as a single agent; or
• Previously untreated follicular, CD20-positive, B-cell NHL in combination with first line chemotherapy and, in individuals achieving a complete or partial response to a rituximab product in combination with chemotherapy, as a single agent maintenance therapy; or
• Non-progressive (including stable disease), low-grade, CD20-positive, B-cell NHL as a single agent after first-line cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy; or
• Previously untreated DLBCL, CD20-positive NHL in combination with CHOP or anthracycline-based chemotherapy regimens; or

Rheumatoid Arthritis (RA)

• As therapy in combination with methotrexate, or other conventional synthetic DMARD if methotrexate is contraindicated, for moderately-to-severely-active RA who have had an inadequate response to one or more TNF antagonist therapies:
  • Combination therapy with methotrexate or other conventional synthetic DMARD not applicable to individuals who have had an inadequate response to methotrexate or other conventional synthetic DMARDs.

Compendia Sources
Rituximab-arrx (Riabni) may be considered medically necessary for treatment of any of the current category 1, 2A, or 2B NCCN recommendations

Reauthorization Criteria for rituximab-arrx (Riabni) 

Continuation of therapy with rituximab-arrx (Riabni) for non-oncologic indications may be considered medically necessary when the following criteria is met:

• The individual has one of the above diagnoses; and
• For RA only; individual has had an adequate therapeutic trial and experienced a documented drug therapy failure or intolerance to the preferred product; and
• Provider attestation that individual has demonstrated a disease stability or beneficial response to therapy; and
• Reauthorization valid for 12 months.

The use of rituximab-arrx (Riabni) for all other indications not listed on this policy is considered experimental/investigational and therefore, not covered. Scientific evidence does not support the use for all other indications.

*Maintenance rituximab is not appropriate after bendamustine and rituximab therapy and has not been tested after VR-CAP (bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone) or RBAC (rituximab, bendamustine and cytarabine) therapy.

NOTE: In addition to the above criteria, product specific dosage and/or frequency limits may apply in accordance with the U.S. Food and Drug Administration (FDA)-approved product prescribing information, national compendia, Centers for Medicare and Medicaid Services (CMS) and other peer reviewed resources or evidence-based guidelines. Highmark may deny, in full or in part, reimbursement for utilization that does not fall within the applicable dosage and/or frequency limits.