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)    Rituximab biosimilar products (Truxima and Ruxience) and Rituxan Hycela require preauthorization when used for diagnoses other than malignant lymphomas, Waldenstrom’s Macroglobulinemia, Wegener’s granulomatosis, Sjogren’s syndrome, primary thrombocytopenia, or post-transplant lymph proliferative disorder.

2)    Riabni (rituximab-arrx), a biosimilar product, requires prior authorization for all use. Riabni is only approved if both Truxima and Ruxience have been tried and clinically significant adverse effects are experienced or those products are contraindicated.

3)    Rituxan (brand name) requires prior-authorization for all use. All Rituxan renewal/continuation requests also require documentation of trial of a biosimilar.  If trial of a biosimilar product is not considered to be suitable for the member, then the provider needs to submit a clinical rationale with relevant clinical literature.

4)    Rituximab is a chemotherapy agent administered intravenously in an infusion.

1)    Rituximab products are administered weekly for 4 to 8 doses.

2)     Rituximab biosimilar (Truxima/Ruxience) and Rituxan Hycela are  considered medically necessary for any of the following indications and does not require preauthorization:

A.   Treatment of non-Hodgkin`s lymphoma and Other Malignant Lymphomas (C82.00–C86.6, C91.40–C91.42, C96.0–C96.2, C96.A); or

B.   Waldenström`s Macroglobulinemia (C88.0); or

C.   Sjogren’s syndrome (M35.00–M35.09); or

D.   Primary thrombocytopenia (D47.3); or

E.   Second-line treatment of persons with CD20 positive chronic lymphocytic leukemia that has relapsed or failed other treatments; or

F.    Philadelphia chromosome-negative acute lymphocytic leukemia for patients aged at least 40 years as a component of HyperCVAD; or

G.   Intra-CSF treatment for leptomeningeal metastases from lymphomas; or

H.   Nodular lymphocyte-predominant Hodgkin lymphoma (C81.01)

3)    Rituximab biosimilar (Truxima/Ruxience) and Rituxan Hycela are considered medically necessary and is covered with preauthorization for any of the following indications:

A.   Treatment immune or idiopathic thrombocytopenic purpura that has relapsed or failed other treatments; or

B.   Treatment of Wegener’s Granulomatosis (M31.30), in combination with glucocorticoids; or

C.   Anti-Neutrophil Cytoplasmic Antibody Vasculitis (ANCA) in combination with glucocorticoids; or

D.   Autoimmune hemolytic anemia in patients who have failed corticosteroid therapy; or

E.   Catastrophic antiphospholipid antibody syndrome (CAPS); or

F.    Cryoglobulinemic vasculitis associated with hepatitis C infection; or

G.   Dermatomyositis after falure of corticosteroid and immunosuppressive therapy; or

H.   Ebstein-Barr virus infection in patients with X-linked immunodeficiency; or

I.     Treatment of Evan’s syndrome in patients who are unresponsive to or unable to tolerate corticosteroids; or

J.    Steroid refractory chronic graft vs. host disease; or

K.   Multicentric Castleman disease in HIV positive patients; or

L.    Membranous Glomerulonephropathy in patients refractor to or unable to tolerate alkylating agents or calcineurin inhibitors; or

M.  Monoclonal gammopathy of unknown significance with polyneuropathy, in patients refractory to standard therapy; or

N.   Multifocal motor neuropathy in patients refractory to IVIg; or

O.   Neuromyelitis optica  refractory to immunosuppressive drugs and/or plasmapheresis; or

P.   Pemphigus vulgaris or pemphigus foliaceus unresponsive to conventional therapy; or

Q.   Relapsing Remitting Multiple Sclerosis; or

R.   Primary Progressive Multiple Sclerosis; or

S.   Post-transplant lymph proliferative disorder; or

T.    Acquired thrombotic thrombocytopenic purpura, due to ADAMTS13 deficiency or gemcitabine induced; or

U.   In transplant patients:

                  i.      Acute heart graft rejection due to antibody mediated disease refractory to plasmapheresis and/or IVIg; or

                ii.      Desensitization of ABO incompatible patients on the renal transplant waiting list, in conjunction with IVIg; or

               iii.      Desensitization of panel reactive antibodies in patients on the renal or cardiac transplant waiting list; or

               iv.      Acute kidney graft rejection due to antibody mediated disease (second line therapy); or

                v.      Acute humoral antibody mediated disease in lung transplant recipients; or

V.   Second line monotherapy or adjunct therapy for the treatment of moderately to severely active rheumatoid arthritis in adults 18 years of age or older who have failed to respond adequately to one of the following disease-modifying anti-rheumatic drugs (DMARDs)(See Limits):

                  i.        Hydroxychloroquine; or

                ii.        Oral or injectable gold; or

               iii.        Methotrexate; or

               iv.        Azathioprine; or

                v.        Leflunomide; or

               vi.        Penicillamine; or

              vii.        Cyclophosphamide; or

             viii.        Sulfasalazine; AND

               ix.        Have failed to respond to two (2) of Cimzia,Humira, Simponi, Xeljanz/XR, or Rinvoq AND

                x.        Have failed to respond to BOTH Actemra and Orencia

4) Riabni (rituximab-arrx), a biosimilar product, requires prior authorization for all use. Riabni is only approved if both Truxima and Ruxience have been tried and clinically significant adverse effects are experienced or those products are contraindicated.

5) Rituxan (brand name) requires prior authorization for any use, requiring previous trial of Truxima or Ruxience (rituximab biosimilar) before approval. All Rituxan renewal/continuation requests also require documentation of trial of a biosimilar.  If trial of a biosimilar product is not considered to be suitable for the member, then the provider needs to submit a clinical rationale with relevant clinical literature.

Codes Used In This BI:

J9311   Injection, rituximab 10 mg and hyaluronidase (new code 1/1/19)

J9312   Injection, rituximab 10 mg (new code 1/1/19)

J9310   Rituximab injection (code deleted 1/1/19)

C9467   Injection, rituximab and hyaluronidase, 10mg (code deleted 1/1/19)

Q5115  Injection, rituximab-abbs, biosimilar, (Truxima), 10mg

Q5119  Injection, rituximab-pvvr, biosimilar, (Ruxience), 10mg

Q5123  Injection, rituximab-arrx, biosimilar, (Riabni), 10mg

The efficacy of more than two infusions in 48 weeks in rheumatoid arthritis is unknown.

There is an increased risk of progressive multifocal leukoencephalopathy (PML) in patients treated with Rituxan.

Rituximab (Rituxan) is considered experimental and investigational for any of the following indications because its effectiveness for these indications has not been established (not an all-inclusive list):

• Chronic inflammatory polyneuropathy/IgM-associated polyneuropathy
• Cryoglobulinemia
• Thrombotic thrombocytopenic purpura
• Segmental glomerulosclerosis
• Systemic lupus erythematosus 
• Birdshot Retinochoroidopathy
• Graft-versus-host disease
• Immune complex vasculitis
• Polymyositis
• Sarcoidosis

According to the literature, management of Non-Hodgkin’s Lymphoma (NHL) consists of intermittent treatment when the disease relapses and causes symptoms. The aim is to maximize quality of life by inducing remission, abolishing the symptoms associated with relapse, with minimal treatment side-effects. Cancer-specific treatment is not usually instituted while the patient is asymptomatic (`watchful waiting`). According to available guidelines, first-line therapy of NHL is usually oral chlorambucil (or an equivalent alkylating agent). Second-line treatment is usually an anthracycline-containing chemotherapy regime.

The U.S. Pharmacopoeial Convention (2003) has concluded that rituximab (Rituxan) is accepted for the following off-label indications: a) as first-line treatment of diffuse aggressive NHL; b) treatment of relapsed or refractory diffuse aggressive NHL; c) first-line treatment of intermediate to high-grade NHL; and d) first-line treatment of low-grade NHL.

The U.S. Pharmacopoeial Convention (2002) has concluded that rituximab is also effective for second-line treatment of patients with relapsed or refractory CD20 positive chronic lymphocytic leukemia (CLL). Chronic lymphocytic leukemia is essentially the bloodstream form of non-Hodgkin`s lymphoma, and is the most common type of leukemia. The disease usually progresses slowly and many people with chronic lymphocytic leukemia do not need treatment for months or years. Chronic lymphocytic leukemia mainly affects older people and is rare in people under age 40.

The U.S. Pharmacopoeial Convention has concluded that rituximab is indicated for treatment of Waldenström`s Macroglobulinemia

Rituximab has been investigated for use in a number of other indications, including thrombotic thrombocytopenic purpura, cryoglobulinemia, chronic inflammatory polyneuropathy, multiple myeloma, idiopathic autoimmune hemolytic anemia, and rheumatoid arthritis.

Rituximab has been investigated for use in thrombotic thrombocytopenic purpura. However, current evidence is limited to case reports and small case series (Yomtovian, et al., 2004).

The evidence for use of rituximab in autoimmune hemolytic anemia is also limited to case reports and small, uncontrolled clinical studies.

Rituximab has also been investigated in the treatment of cryoglobulinemia (see, e.g., Zaja, et al., 2003; Sansonno, et al., 2003; Arzoo, et al., 2002; Baronciani, et al., 2002). However, controlled studies are needed to better define the value of rituximab for this indication (Zaja, et al., 2003). Consensus Panel Recommendations from the Second International Workshop on Waldenström`s Macroglobulinemia (Gertz, et al., 2003) did not list rituximab among effective interventions for symptomatic mixed cryoglobulinemia (MC).

A recently published Cochrane systematic evidence review (Hughes, et al., 2003) concluded that there is inadequate evidence of the effectiveness of rituximab in the treatment of chronic inflammatory polyneuropathy.

Edwards, et al. (2004)33 reported on the results of an multicenter randomized controlled clinical trial of rituximab in rheumatoid arthritis, which found that a single course of two infusions of rituximab alone or in combination provided significant improvement in disease symptoms for 48 weeks.

The investigators concluded that, in patients with active rheumatoid arthritis despite methotrexate treatment, a single course of two infusions of rituximab, alone or in combination with either cyclophosphamide or continued methotrexate, provided significant improvement in disease symptoms at both 24 and 48 weeks.

1.    Coiffier B, Haioun C, Ketterer N, et al. Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with relapsing or refractory aggressive lymphoma: A multicenter phase II study. Blood. 1998; 92(6):1927-1932.

2.    IDEC Pharmaceuticals Corporation and Genentec, Inc. prescribing information for Rituxan™ (rituximab). South San Francisco, CA: Genentec, Inc.; September 1998.

3.    Maloney DG, Grillo-López AJ, White CA, et al. IDEC-C2B8 (Rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin`s lymphoma. Blood. 1997; 90(6):2188-2195.

4.    Byrd JC, Waselenko JK, Maneatis TJ, et al. Rituximab therapy in hematologic malignancy patients with circulating blood tumor cells: Association with increased infusion-related side effects and rapid blood tumor clearance. J Clin Oncol. 1999; 17(3):791-795.

5.    Nguyen DT, Amess JA, Doughty H, et al. IDEC-C2B8 anti-CD20 (rituximab) immunotherapy in patients with low-grade non-Hodgkin`s lymphoma and lymphoproliferative disorders: Evaluation of response on 48 patients. Eur J Haematol. 1999; 62(2):76-82.

6.    National Cancer Institute. Chronic Lymphocytic Leukemia (PDQ): Treatment. Bethesda, MD: NCI; January 2002. Available at: http://www.cancer.gov/cancer_information/doc.aspx?version=provider&viewid=e1a644a1-d741-4a32-af02-96aedd6d1922

7.    Perry M, Rasool H. Chronic lymphocytic leukemia. eMedicine J. 2001; 2(12). Available at: http://www.emedicine.com/med/topic370.htm .

8.    Dimopoulos MA, Zervas C, Zomas A, et al. Treatment of Waldenstrom`s Macroglobulinemia with rituximab. J Clin Oncol. 2002; 20(9):2327-2333.

9.    Giagounidis AA, Anhuf J, Schneider P, et al. Treatment of relapsed idiopathic thrombocytopenic purpura with the anti-CD20 monoclonal antibody rituximab: A pilot study. Eur J Haematol. 2002; 69(2):95-100.

10.   Meo P, Stipa E, La Presa M, et al. [Rituximab treatment of chronic idiopathic thrombocytopenic purpura. Results of a phase II study]. Recenti Prog Med. 2002; 93(7-8):421-427.

11.   Zaja F, Iacona I, Masolini P, et al. B-cell depletion with rituximab as treatment for immune hemolytic anemia and chronic thrombocytopenia. Haematologica. 2002; 87(2):189-195.

12.   Stasi R, Pagano A, Stipa E, Amadori S. Rituximab chimeric anti-CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura. Blood. 2001; 98(4):952-957.

13.   Zaja F, Vianelli N, Sperotto A, et al. B-cell compartment as the selective target for the treatment of immune thrombocytopenia’s. Haematologica. 2003; 88(5):538-546.

14.   Kneitz C, Wilhelm M, Tony HP. Effective B cell depletion with rituximab in the treatment of autoimmune diseases. Immunobiology. 2002; 206(5):519-527.

15.   Vesely SK, Perdue JJ, Rizvi MA, et al. Management of adult patients with persistent idiopathic thrombocytopenic purpura following splenectomy: A systematic review. Ann Intern Med. 2004; 140(2):112-120.

16.   National Horizon Scanning Centre. Rituximab for aggressive B-cell lymphoma. Birmingham, UK: National Horizon Scanning Centre (NHSC); 2002.

17.   Sansonno D, De Re V, Lauletta G, et al. Monoclonal antibody treatment of mixed cryoglobulinemia resistant to interferon alpha with an anti-CD20. Blood. 2003; 101(10):3818-3826.

18.   Gertz MA, Anagnostopoulos A, Anderson K, et al. Treatment recommendations in Waldenstrom`s Macroglobulinemia: Consensus panel recommendations from the Second International Workshop on Waldenstrom`s Macroglobulinemia. Semin Oncol. 2003; 30(2):121-126.

19.   Arzoo K, Sadeghi S, Liebman HA. Treatment of refractory antibody mediated autoimmune disorders with an anti-CD20 monoclonal antibody (rituximab). Ann Rheum Dis. 2002; 61(10):922-924.

20.   Rituximab Quartier P, Brethon B, Philippet P, et al. Treatment of childhood autoimmune hemolytic anemia with rituximab. Lancet. 2001; 358(9292):1511-1513.

21.   Arzoo K, Sadeghi S, Liebman HA. Treatment of refractory antibody mediated autoimmune disorders with an anti-CD20 monoclonal antibody (rituximab). Ann Rheum Dis. 2002; 61(10):922-924.

22.   Zaja F, Iacona I, Masolini P, et al. B-cell depletion with rituximab as treatment for immune hemolytic anemia and chronic thrombocytopenia. Haematologica. 2002; 87(2):189-195.

23.   Wakim M, Shah A, Arndt PA, et al. Successful anti-CD20 monoclonal antibody treatment of severe autoimmune hemolytic anemia due to warm reactive IgM autoantibody in a child with common variable immunodeficiency. Am J Hematol. 2004; 76(2):152-155.

24.   Raj A, Bertolone S, Cheerva A. Successful treatment of refractory autoimmune hemolytic anemia with monthly rituximab following nonmyeloablative stem cell transplantation for sickle cell disease. J Pediatr Hematol Oncol. 2004; 26(5):312-314.

25.   Webster D, Ritchie B, Mant MJ. Prompt response to rituximab of severe hemolytic anemia with both cold and warm autoantibodies. Am J Hematol. 2004; 75(4):258-259.

26.   Etienne A, Gayet S, Vidal F, et al. Severe hemolytic anemia due to cold agglutinin complicating untreated chronic hepatitis C: Efficacy and safety of anti-CD20 (rituximab) treatment. Am J Hematol. 2004; 75(4):243-245.

27.   Kornberg AJ, Pestronk A. Antibody-associated polyneuropathy syndromes: Principles and treatment. Semin Neurol. 2003; 23(2):181-190.

28.   Pestronk A, Florence J, Miller T, et al. Treatment of IgM antibody associated polyneuropathies using rituximab. J Neurol Neurosurg Psychiatry. 2003; 74(4):485-489.

29.   Hughes RA, Swan AV, van Doorn PA. Cytotoxic drugs and interferon’s for chronic inflammatory demyelinating polyradiculoneuropathy. Cochrane Database Syst Rev. 2003; (1):CD003280.

30.   Taylor PC. Antibody therapy for rheumatoid arthritis. Curr Opin Pharmacol. 2003; 3(3):323-328.

31.   Shaw T, Quan J, Totoritis MC. B cell therapy for rheumatoid arthritis: The rituximab (anti-CD20) experience. Ann Rheum Dis. 2003; 62 Suppl 2:ii55-59.

32.   Tsai HM, Shulman K. Rituximab induces remission of cerebral ischemia caused by thrombotic thrombocytopenic purpura. Eur J Haematol. 2003; 70(3):183-185.

33.   Edwards JC, Szczepanski L, Szechinski J, et al. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med. 2004; 350(25):2572-2581.

34.   Tsokos GC. B cells, be gone--B-cell depletion in the treatment of rheumatoid arthritis. N Engl J Med. 2004; 350(25):2546-2548.

35.   BlueCross BlueShield Association (BCBSA), Technology Evaluation Center (TEC). Rituximab for treatment of intermediate and aggressive B-cell non-Hodgkin`s lymphomas. TEC Assessment Program. Chicago IL: BCBSA; 2002.

36.   National Horizon Scanning Centre (NHSC). Rituximab for 1st line low-grade non-Hodgkin`s lymphoma. Birmingham, UK: NHSC; 2004.

37.   Knight C, Hind D, Brewer N, Abbott V. Rituximab (MabThera) for aggressive non-Hodgkin`s lymphoma: Systematic review and economic evaluation. Health Technol Assess. 2004; 8(37):1-96.

38.   Benz K, Dotsch J, Rascher W, Stachel D. Change of the course of steroid-dependent nephrotic syndrome after rituximab therapy. Pediatr Nephrol. 2004; 19(7):794-797.

39.   Looney RJ, Anolik JH, Campbell D, et al. B cell depletion as a novel treatment for systemic lupus erythematosus: A phase I/II dose-escalation trial of rituximab. Arthritis Rheum. 2004; 50(8):2580-2589.

40.   Tallman MS, Zakarija A. Hairy cell leukemia: Survival and relapse. Long-term follow-up of purine analog-based therapy and approach for relapsed disease. Transfus Apher Sci. 2005; 32(1):99-103.

41.   Cree BA, Lamb S, Morgan K, et al. An open label study of the effects of rituximab in neuromyelitis optica. Neurology. 2005; 64(7):1270-1272.

42.   Omdal R, Wildhagen K, Hansen T, et al. Anti-CD20 therapy of treatment-resistant Wegener`s granulomatosis: Favorable but temporary response. Scand J Rheumatol. 2005; 34(3):229-232.

43.   Eriksson P. Nine patients with anti-neutrophil cytoplasmic antibody-positive vasculitis successfully treated with rituximab. J Intern Med. 2005; 257(6):540-548.

44.   Marks SD, Patey S, Brogan PA, et al. B lymphocyte depletion therapy in children with refractory systemic lupus erythematosus. Arthritis Rheum. 2005; 52(10):3168-3174.

45.   Sfikakis PP, Boletis JN, Tsokos GC. Rituximab anti-B-cell therapy in systemic lupus erythematosus: Pointing to the future. Curr Opin Rheumatol. 2005; 17(5):550-557.

46.   Anolik JH, Aringer M. New treatments for SLE: Cell-depleting and anti-cytokine therapies. Best Pract Res Clin Rheumatol. 2005; 19(5):859-878.

47.   Leandro MJ, Cambridge G, Edwards JC, et al. B-cell depletion in the treatment of patients with systemic lupus erythematosus: A longitudinal analysis of 24 patients. Rheumatology (Oxford). 2005; 44(12):1542-1545.

48.   Levine TD. Rituximab in the treatment of dermatomyositis: An open-label pilot study. Arthritis Rheum. 2005; 52(2):601-607.

49.   Looney RJ. B cell-targeted therapy in diseases other than rheumatoid arthritis. J Rheumatol Suppl. 2005; 73:25-28; discussion 29-30.

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51.   Hawker, K et al.  Rituximab in patients with primary progressive multiple sclerosis: Results of a randomized double-blind placebo-controlled multicenter trial. Ann Neurol. 2009; 66: 460–471.

Addendum: 

1)    Effective 09/01/2017: Added indication for Primary Progressive Multiple Sclerosis.

2)    Effective 05/01/2018: Added Rituxan Hycela to coverage policy.

3)    Effective 01/01/2019: 2019 Code Updates. Deleted HCPCS codes J9310 & C9467 and replaced with new HCPCS codes J9311 – J9312.

4)    Effective 01/01/2020: Updated prerequisite drugs for use of rituximab in RA.

5)    Effective 06/01/2020: Updated coverage policy to require trial of Truxima (rituximab biosimilar) before brand name Rituxan is approved.

6)    Effective 07/01/2020: Updated to add Q5119 (Ruxience).

7)    Effective 7/1/2022: Updated to add coverage criteria for Q5123 (Riabni).

8)    Effective 10/01/2023: Updated E/I list in criteria.