Rituximab Products (Rituxan®, Rituximab-abbs [Truxima®],Rituximab-arrx [Riabni™] and Rituximab-pvvr [Ruxience®])
Treatment of Rheumatoid Arthritis and Other Conditions (Non-Oncolgy Indications)
Some agents on this policy may require step therapy See “Step Therapy Requirements for Provider Administered Specialty Medications” Document at: https://www.bcbst.com/docs/providers/Comm_BC_PAD_Step_Therapy_Guide.pdf
IMPORTANT REMINDER
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the medical policy and a health plan or government program (e.g., TennCare), the express terms of the health plan or government program will govern.
POLICY
I. INDICATIONS
The indications below including FDA-approved indications and compendial uses are considered a covered benefit provided that all the approval criteria are met and the member has no exclusions to the prescribed therapy.
A. FDA-Approved Indications
Rituxan, Ruxience, Truxima, and Riabni are indicated for:
1. Granulomatosis with Polyangiitis (GPA) (Wegener’s Granulomatosis) and Microscopic Polyangiitis (MPA) in adult and pediatric patients 2 years of age and older* in combination with glucocorticoids (*pediatric indication applies to Rituxan only).
2. Rheumatoid Arthritis (RA) in combination with methotrexate in adult patients with moderately-to severely-active RA who have inadequate response to one or more TNF antagonist therapies.
3. Non-Hodgkin’s lymphoma (NHL)
(Not addressed in this policy – Refer to Rituxan-Ruxience-Truxima-Riabni-Oncology SGM)
4. Chronic lymphocytic leukemia (CLL)
(Not addressed in this policy – Refer to Rituxan-Ruxience-Truxima-Riabni-Oncology SGM)
Rituxan is also indicated for:
1. Pemphigus Vulgaris (PV)
Rituxan is indicated for the treatment of adult patients with moderate to severe pemphigus vulgaris.
2. Mature B-cell acute leukemia (B-AL)
(Not addressed in this policy - Refer to Rituxan-Ruxience-Truxima-Riabni Oncology SGM)
B. Compendial Uses
1. Sjögren’s syndrome
2. Multiple sclerosis, relapsing remitting
3. Neuromyelitis optica (i.e. neuromyelitis optica spectrum disorder, NMOSD, Devic disease)
4. Autoimmune blistering disease
5. Cryoglobulinemia
6. Solid organ transplant
7. Opsoclonus-myoclonus ataxia
8. Systemic lupus erythematosus
9. Myasthenia gravis, refractory
10. For other compendial uses, refer to Rituxan-Ruxience-Truxima-Riabni-Oncology SGM
All other indications are considered experimental/investigational and not medically necessary.
II. DOCUMENTATION
Submission of the following information is necessary to initiate the prior authorization review:
A. Rheumatoid arthritis (RA)
1. Initial requests:
i. Chart notes, medical record documentation, or claims history supporting previous medications tried (if applicable), including response to therapy. If therapy is not advisable, documentation of clinical reason to avoid therapy.
ii. Laboratory results, chart notes, or medical record documentation of biomarker testing (i.e., rheumatoid factor [RF], anti-cyclic citrullinated peptide [anti-CCP], and C-reactive protein [CRP] and/or erythrocyte sedimentation rate [ESR]) (if applicable).
2. Continuation requests: Chart notes or medical record documentation supporting positive clinical response.
B. Sjögren’s syndrome, cryoglobulinemia, opsoclonus-myoclonus-ataxia, and systemic lupus erythematosus (initial requests only): Chart notes, medical record documentation, or claims history supporting previous medications tried, including response to therapy.
III. PRESCRIBER SPECIALITIES
This medication must be prescribed by or in consultation with one of the following:
A. RA, GPA (Wegener’s granulomatosis), MPA, Churg-Strauss, pauci-immune glomerulonephritis, SLE: rheumatologist, immunologist, nephrologist
B. Sjogren’s syndrome: rheumatologist, ophthalmologist, immunologist
C. Multiple sclerosis, NMOSD, myasthenia gravis, opsoclonus-myoclonus-ataxia: neurologist, immunologist
D. Autoimmune blistering disease: dermatologist, immunologist
E. Cryoglobulinemia: hematologist, rheumatologist, neurologist, nephrologist
F. Solid organ transplant: immunologist, transplant specialist
IV. EXCLUSIONS
A. Coverage will not be provided for requests for the treatment of rheumatoid arthritis (RA) when planned date of administration is less than 16 weeks since date of last dose received.
B. Member will not receive Rituxan, Ruxience, Truxima, or Riabni with other biologics for RA.
C. Member will not receive Rituxan, Ruxience, Truxima, or Riabni with other multiple sclerosis (MS) drugs excluding Ampyra.
D. Member will not use Rituxan, Ruxience, Truxima, or Riabni concomitantly with other biologics for the treatment of neuromyelitis optica.
V. CRITERIA FOR INITIAL APPROVAL
A. Rheumatoid arthritis (RA)
1. Authorization of 12 months may be granted for the treatment of adults with moderately to severely active rheumatoid arthritis (RA) in combination with methotrexate (MTX) or leflunomide unless the
member has a contraindication (see VII. Appendix) or intolerance to MTX or leflunomide and either of the following criteria are met:
i. The member has previously received a biologic or targeted synthetic drug (e.g., Rinvoq, Xeljanz) indicated for the treatment of moderately to severely active rheumatoid arthritis; or
ii. The member has received at least two full doses of Rituxan, Ruxience, Truxima, or Riabni for the treatment of RA, where the most recent dose was given within 6 months of the request.
2. Authorization of 12 months may be granted for treatment of adults with moderately to severely active RA in combination with MTX or leflunomide unless the member has a contraindication (see VII. Appendix) or intolerance to MTX or leflunomide when all of the following criteria are met:
i. The member meets either of the following criteria:
a. The member has been tested for either of the following biomarkers and the test was positive:
1. Rheumatoid factor (RF)
2. Anti-cyclic citrullinated peptide (anti-CCP)
b. The member has been tested for ALL of the following biomarkers:
1. RF
2. Anti-CCP
3. C-reactive protein (CRP) and/or erythrocyte sedimentation rate (ESR)
ii. The member meets either of the following criteria:
a. The member has experienced an inadequate response to at least a 3-month trial of MTX despite adequate dosing (i.e., titrated to at least 15 mg/week); or
b. The member had an intolerable adverse effect or contraindication to MTX (see VII. Appendix), and an inadequate response to another conventional drug (e.g., hydroxychloroquine, leflunomide, sulfasalazine).
B. Granulomatosis with polyangiitis (GPA) (Wegener’s granulomatosis) and microscopic polyangiitis (MPA) and Churg-Strauss and pauci-immune glomerulonephritis
Authorization of 12 months may be granted for treatment of GPA, MPA, Churg-Strauss, or pauci-immune glomerulonephritis.
C. Sjögren’s syndrome
Authorization of 12 months may be granted for treatment of Sjögren’s syndrome when corticosteroids and other immunosuppressive agents were ineffective.
D. Multiple sclerosis
Authorization of 12 months may be granted for treatment of relapsing remitting multiple sclerosis (MS).
E. Neuromyelitis optica (i.e., neuromyelitis optica spectrum disorder; NMOSD, Devic Disease)
Authorization of 12 months may be granted for treatment of neuromyelitis optica (i.e., neuromyelitis optica spectrum disorder; NMOSD, Devic disease).
F. Autoimmune blistering disease
Authorization of 12 months may be granted for treatment of autoimmune blistering disease (e.g., pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid, cicatricial pemphigoid, epidermolysis bullosa acquisita and paraneoplastic pemphigus).
G. Cryoglobulinemia
Authorization of 12 months may be granted for treatment of cryoglobulinemia when corticosteroids and other immunosuppressive agents were ineffective.
H. Solid organ transplant
Authorization of 3 months may be granted for treatment of solid organ transplant and prevention of antibody mediated rejection in solid organ transplant.
I. Opsoclonus-myoclonus-ataxia
Authorization of 12 months may be granted for treatment of opsoclonus-myoclonus-ataxia associated with neuroblastoma when the member is refractory to steroids and chemotherapy.
J. Systemic Lupus Erythematosus
Authorization of 12 months may be granted for the treatment of systemic lupus erythematosus that is refractory to immunosuppressive therapy.
K. Myasthenia Gravis
Authorization of 12 months may be granted for treatment of refractory myasthenia gravis.
VI. CONTINUATION OF THERAPY
A. Rheumatoid arthritis
Authorization of 12 months may be granted for continued treatment in all adult members (including new members) requesting reauthorization who meet all initial authorization criteria and achieve or maintain positive clinical response after at least two doses of therapy with Rituxan, Ruxience, Truxima, or Riabni as evidenced by disease activity improvement of at least 20% from baseline in tender joint count, swollen joint count, pain, or disability.
B. Multiple Sclerosis
Authorization of 12 months may be granted for continued treatment in members requesting reauthorization for relapsing remitting multiple sclerosis (MS) who are experiencing disease stability or improvement while receiving Rituxan, Ruxience, Truxima, or Riabni.
C. Other indications
Authorization of 12 months may be granted for continued treatment in all members (including new members) requesting reauthorization who meet all initial authorization criteria and are receiving benefit from therapy.
VII. APPENDIX
Examples of contraindications to methotrexate and leflunomide
1. Clinical diagnosis of alcohol use disorder, alcoholic liver disease or other chronic liver disease
2. Breastfeeding
3. Blood dyscrasias (e.g., thrombocytopenia, leukopenia, significant anemia)
4. Elevated liver transaminases
5. History of intolerance or adverse event
6. Hypersensitivity
7. Interstitial pneumonitis or clinically significant pulmonary fibrosis
8. Myelodysplasia
9. Pregnancy or currently planning pregnancy
10. Renal impairment
11. Significant drug interaction
MEDICATION QUANTITY LIMITS
Drug Name |
Diagnosis |
Maximum Dosing Regimen |
Rituxan (Rituximab) Riabni (Rituximab-arrx) Ruxience (Rituximab-pvvr) Truxima (Rituximab-abbs) |
Cryoglobulinemia, Multiple Sclerosis, Myasthenia Gravis, Neuromyelitis Optica (i.e. Neuromyelitis Optica Spectrum Disorder, NMOSD, or Devic Disease), Opsoclonus-Myoclonus Ataxia, Sjögren’s Syndrome, Solid Organ Transplant, Systemic Lupus Erythematosus |
Route of Administration: Intravenous 1000mg (frequency should not be more frequent than every 14 days) |
Rituxan (Rituximab) |
Granulomatosis with Polyangiitis (GPA) (Wegener’s Granulomatosis) and Microscopic Polyangiitis (MPA) |
Route of Administration: Intravenous 2-17 Years 375mg/m² every week for 4 weeks, followed by 250 mg/m2 every 2 weeks for 2 doses (start no sooner than 16 to 24 weeks after last induction dose), followed by 250 mg/m2 every 6 months based on clinical evaluation
≥18 Years 375mg/m² every week for 4 weeks, followed by 500 mg every 2 weeks for 2 doses (start no sooner than 16 to 24 weeks after last induction dose), followed by 500 mg every 6 months based on clinical evaluation |
Riabni (Rituximab-arrx) Ruxience (Rituximab-pvvr) Truxima (Rituximab-abbs) |
Granulomatosis with Polyangiitis (GPA) (Wegener’s Granulomatosis) and Microscopic Polyangiitis (MPA) |
Route of Administration: Intravenous ≥18 Years 375mg/m² every week for 4 weeks, followed by 500 mg every 2 weeks for 2 doses (start no sooner than 16 to 24 weeks after last induction dose), followed by 500 mg every 6 months based on clinical evaluation |
Rituxan (Rituximab)
|
Pemphigus Vulgaris (PV) and other Autoimmune Blistering Disease (e.g., Pemphigus Foliaceus, Bullous Pemphigoid, Cicatricial Pemphigoid, Epidermolysis Bullosa Acquisita and Paraneoplastic Pemphigus) |
Route of Administration: Intravenous ≥18 Years Initial: 1000mg every 2 weeks for 2 doses, followed by Maintenance: 500mg at month 12 and every 6 months thereafter
≥18 Years 1000mg on relapse; subsequent infusions no sooner than 16 weeks following previous infusion |
Rituxan (Rituximab) Riabni (Rituximab-arrx) Ruxience (Rituximab-pvvr) Truxima (Rituximab-abbs) |
Rheumatoid Arthritis |
Route of Administration: Intravenous ≥18 Years Initial: 1000mg every 2 weeks for 2 doses Maintenance: 1000mg every 24 weeks or based on clinical evaluation, but not sooner than every 16 weeks |
APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS
BlueCross BlueShield of Tennessee’s Medical Policy complies with Tennessee Code Annotated Section 56-7-2352 regarding coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is recognized in one of the statutorily recognized standard reference compendia or in the published peer-reviewed medical literature.
ADDITIONAL INFORMATION
For appropriate chemotherapy regimens, dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) published by the National Comprehensive Cancer Network®, Drugdex Evaluations of Micromedex Solutions at Truven Health, or The American Hospital Formulary Service Drug Information).
REFERENCES
1. Rituxan [package insert]. South San Francisco, CA: Genentech, Inc.; December 2021.
2. Truxima [package insert]. North Wales, PA: Teva Pharmaceuticals USA, Inc.; February 2022.
3. Methotrexate [package insert]. Cranbury, NJ: Sun Pharmaceutical Industries, Inc.; August 2021.
4. IBM Micromedex [Internet database]. Ann Arbor, MI: Truven Health Analytics. Updated periodically. Accessed April 3, 2023.
5. Dass S, Bowman SJ, Vital EM, et al. Reduction of fatigue in Sjögren syndrome with rituximab: results of a double blind, placebo-controlled study. Ann Rheum Dis. 2008;67:1541-1544.
6. Meijer JM, Meiners PM, Vissink A, et al. Effectiveness of rituximab treatment in primary Sjögren's syndrome: a randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2010;62(4):960-8.
7. Smolen JS, Landewé R, Billsma J, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis. 2020;79:685-699.
8. Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol. 2016;68(1)1-26.
9. Saag KG, Teng GG, Patkar NM, et al. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum. 2008;59(6):762-784.
10. Hauser SL, Waubant E, Arnold DL, et al. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med. 2008;358:676-688.
11. Scott, T.F., Frohman, E.M., DeSeze, J., (2011). Evidence-based guideline: Clinical evaluation and treatment of transverse myelitis: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. American Academy of Neurology. 77: 2128-2134.
12. Trebst, C., Jarius, S., et al. (2014). Update on the diagnosis and treatment of neuromyelitis optica: Recommendations of the Neuromyelitis Optica Study Group (NEMOS). J Neurol 261: 1-16.
13. De Vita S, Quartuccio L, Isola M, et al. A randomized controlled trial of rituximab for the treatment of severe cryoglobulinemic vasculitis. Arthritis Rheum. 2012;64(3):843-53.
14. Sneller MC, Hu Z, Langford CA. A randomized controlled trial of rituximab following failure of antiviral therapy for hepatitis C virus-associated cryoglobulinemic vasculitis. Arthritis Rheum. 2012 Mar; 64(3):835-42.
15. Terrier B, Krastinova E, Marie I, et al. Management of noninfectious mixed cryoglobulinemia vasculitis: data from 242 cases included in the CryoVas survey. Blood. 2012 Jun 21; 119(25):5996-6004.
16. Trappe R, Oertel S, Leblond V, et al. Sequential treatment with rituximab followed by CHOP chemotherapy in adult B-cell post-transplant lymphoproliferative disorder (PTLD): the prospective international multicentre phase 2 PTLD-1 trial. Lancet Oncol 2012.
17. The American Society of Transplantation Infectious Diseases Guidelines. Am J Transplant 2009; 9 (Suppl 4):S92.
18. Bell J, Moran C, Blatt J. Response to rituximab in a child with neuroblastoma and opsoclonus-myoclonus. Pediatr Blood Cancer 2008; 50:370.
19. Hertl M, Geller S. Initial management of pemphigus vulgaris and pemphigus foliaceus. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed August 2021.
20. American Society of Health System Pharmacists. AHFS DI. Bethesda, MD. Electronic version, 2019. Available with subscription. URL: http://online.lexi.com/lco/action/home. Accessed April 3, 2023.
21. DRUGDEX System (electronic version). Micromedex Truven Health Analytics. Available with subscription. URL: www.micromedexsolutions.com. Accessed April 3, 2023.
22. Ruxience [package insert]. NY, NY: Pfizer Biosimilars; November 2021.
23. Riabni [package insert]. Thousand Oaks, CA: Amgen Inc.; June 2022.
24. Aletaha D, Neogi T, Silman, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62(9):2569-81.
25. Smolen JS, Aletaha D. Assessment of rheumatoid arthritis activity in clinical trials and clinical practice. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. Available with subscription. URL: www.uptodate.com. Accessed November 7, 2022.
26. Murrell DF, Peña S, Joly P, et al. Diagnosis and management of pemphigus: Recommendations of an international panel of experts. J Am Acad Dermatol. 2020;82(3):575-585.e1.
27. Joly P, Horvath B, Patsatsi Α, et al. Updated S2K guidelines on the management of pemphigus vulgaris and foliaceus initiated by the european academy of dermatology and venereology (EADV). J Eur Acad Dermatol Venereol. 2020;34(9):1900-1913.
28. Micromedex Solutions [database online]. Truven Health Analytics, Greenwood Village, Colorado, USA. Available at: http://www.micromedexsolutions.com/. Accessed April 3, 2023.
29. Fraenkel L, Bathon JM, England BR, et al. 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthrit Care Res. 2021;0:1-16.
30. Menditto VG, Rossetti G, Olivari D, et al. Rituximab for eosinophilic granulomatosis with polyangiitis: a systematic review of observational studies. Rheumatology (Oxford). 2021;60(4):1640-1650.
31. Chung SA, Langford CA, Maz M, et al. 2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. Arthritis Rheumatol. 2021;73(8):1366-1383.
32. Poupart J, Giovannelli J, Deschamps R, Audoin B, Ciron J, Maillart E, Papeix C, Collongues N, Bourre B, Cohen M, Wiertlewski S, Outteryck O, Laplaud D, Vukusic S, Marignier R, Zephir H; NOMADMUS study group. Evaluation of efficacy and tolerability of first-line therapies in NMOSD. Neurology. 2020 Apr 14;94(15):e1645-e1656.
ORIGINAL EFFECTIVE DATE: 2/26/2003
MOST RECENT REVIEW DATE: 4/1/2024
ID_CHS
Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.
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