Notification



Notification Issue Date:



Policy Attachment

Attachment to Policy # MA08.019f


Attachment:A

Policy #:MA08.019f

Description:Dosing and Frequency Requirements for Infliximab and Related Biosimilars

Title:Infliximab and Related Biosimilars

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.


DOSING AND FREQUENCY REQUIREMENTS FOR INFLIXIMAB (REMICADE®) AND RELATED BIOSIMILARS (E.G., INFLIXIMAB-DYYB [INFLECTRA], INFLIXIMAB-ABDA [RENFLEXIS], INFLIXIMAB-QBTX [IXIFI])

The Company reserves the right to modify the Dosing and Frequency Requirements listed in this Policy to ensure consistency with the most recently published recommendations for the use of infliximab and related biosimilars. Changes to these guidelines are based on a consensus of information obtained from resources such as, but not limited to: the US Food and Drug Administration (FDA); Company-recognized authoritative pharmacology compendia; or published peer-reviewed clinical research. The professional provider must supply supporting documentation (ie, published peer-reviewed literature) in order to request coverage for an amount of infliximab or related biosimilars outside of the Dosing and Frequency Requirements listed in this Policy. For a list of Company-recognized pharmacology compendia, view our policy on off-label coverage for prescription drugs and biologics.

Accurate member information is necessary for the Company to approve the requested dose and frequency of this drug. If the member’s dose, frequency, or regimen changes (based on factors such as changes in member weight or incomplete therapeutic response), the provider must submit those changes to the Company for a new approval based on those changes as part of the precertification process. The Company reserves the right to conduct post-payment review and audit procedures for any claims submitted for infliximab or related biosimilars.

Indication
Dosage and Frequency
Anklyosing spondylitis1Induction: 5 mg/kg IV at weeks 0, 2, and 6
Maintenance: 5 mg/kg IV every 6 weeks (up to a maximum of 10 mg/kg IV every 4 weeks)
Crohn's disease (moderate to severe) or fistulizing Crohn's disease1Adults:
Induction: 5 mg/kg IV at weeks 0, 2, and 6
Maintenance: 5 mg/kg IV every 8 weeks. For adults who respond and then lose their response, consideration may be given to treatment with 10 mg/kg IV every 8 weeks (up to a maximum of 10 mg/kg IV every 4 weeks)

Children:
Induction: 5 mg/kg IV at weeks 0, 2, 6
Maintenance: 5 mg/kg IV every 8 weeks (up to a maximum of 10 mg/kg IV every 4 weeks)

For children who are steroid-refractory or have severe extensive or fistulizing disease, especially with hypoalbuminemia, consideration may be given for a higher induction dose of 10mg/kg and/or decreasing the interval between infusions to 4-6 weeks.
Hidradenitis Suppurativa Induction: 5-10 mg/kg IV at weeks 0, 2, and 6
Maintenance: 5-10mg/kg IV every 4 weeks, and with
decreasing dosage as tolerated.
    Toxicities Related to Immune Checkpoint Inhibitors
Infliximab 5mg/kg IV at weeks 0, 2
Inflammatory bowel disease arthritis (enteropathic arthritis)5 Induction: 5 mg/kg IV at weeks 0, 2, and 6
Maintenance: 5 mg/kg IV every 8 weeks (up to a maximum of 10 mg/kg IV every 4 weeks)
Plaque Psoriasis, severe1, 8 Induction: 5 mg/kg IV at weeks 0, 2, and 6
Maintenance: 5 mg/kg IV every 8 weeks (up to a maximum of 10 mg/kg IV every 4 weeks)
Polyarticular Juvenile Idiopathic Arthritis (JIA) 2Induction: 3 to 6 mg/kg IV at weeks 0, 2, and 6
Maintenance: 3 to 6 mg/kg IV every 8 weeks (up to a maximum of 10 mg/kg IV every 4 weeks)
Psoriatic arthritis1Induction: 5 mg/kg IV at weeks 0, 2, and 6
Maintenance: 5 mg/kg IV every 8 weeks (up to a maximum of 10 mg/kg IV every 4 weeks)
Reactive arthritis (Reiter's disease)6 Induction: 3 to 5 mg/kg IV at weeks 0, 2, and 6
Maintenance: 3 to 5 mg/kg IV every 6-8 weeks (up to a maximum of 10 mg/kg IV every 4 weeks)
Rheumatoid arthritis1Induction: 3 mg/kg IV at weeks 0, 2, and 6
Maintenance: 3 mg/kg IV every 8 weeks (up to a maximum of 10 mg/kg IV every 4 weeks)
Pyoderma gangrenosum3Induction: 5 mg/kg IV at week 0. Repeat at week 2 if needed.
Maintenance: 5 mg/kg IV every 4-12 weeks (up to a maximum of 10 mg/kg IV every 4 weeks)
Sarcoidosis, chronic pulmonary 4Induction: 3 to 5 mg/kg IV at weeks 0, 2, and 6
Maintenance: 3 to 5 mg/kg IV every 4 to 8 weeks (up to a maximum of 10 mg/kg IV every 4 weeks)
Ulcerative colitis (adult and pediatric)1Induction: 5 mg/kg IV at weeks 0, 2, and 6
Maintenance: 5 mg/kg IV every 8 weeks (up to a maximum of 10 mg/kg IV every 4 weeks)

For children who are steroid-refractory or have severe extensive or fistulizing disease, especially with hypoalbuminemia, consideration may be given for a higher induction dose of 10mg/kg and/or decreasing the interval between infusions to 4-6 weeks.
Uveitis, non-infectious9 Induction: 3 to 10 mg/kg IV at weeks 0, 2, and 6
Maintenance: 3 to 10 mg/kg IV every 4 to 8 weeks
Wegener’s granulomatosis7Induction: 3 to 5 mg/kg IV at weeks 0, 2, and 6
Maintenance: 3 to 5 mg/kg every 4 to 8 weeks (up to a maximum of 10 mg/kg IV every 4 weeks)

REFERENCES

Brahmer JR, Lacchetti C, Schneider BJ, et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol 2018; 36:1714.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Management of Immune Checkpoint Inhibitor-Related Toxicities. v.1.2019. [NCCN Web site]. 11/14/2018. Available at: https://www.nccn.org/professionals/physician_gls/pdf/immunotherapy.pdf [via subscription only]. Accessed January 25, 2019.

Up to Date. Patient selection criteria and toxicities associated with checkpoint inhibitor immunotherapy. 01/07/19. Available at: http://www.uptodate.com [via subscription only]. Accessed January 31, 2019.

1Remicade (Infliximab) [package insert]. Horsham, PA. Janssen Biotech. Revised October 2017. Available at: http://www.remicade.com/ . Accessed October 30, 2017.

US Food and Drug Administration (FDA). infliximab-abda (Renflexis) prescribing information & approval letter. [FDA Web site]. 04/21/2017. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/ . Accessed September 1, 2017.

US Food and Drug Administration (FDA). infliximab-dyyb (Inflectra) prescribing information & approval letter. [FDA Web site]. 04/05/2016. Available at: http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=BasicSearch.process . Accessed November 14, 2016.

US Food and Drug Administration (FDA). infliximab-qbtx (Ixifi) prescribing information & approval letter. [FDA Web site]. 12/13/2017. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm . Accessed December 14, 2017.

2 Gerloni V, Pontikaki I, Gattinara M, et al. Efficacy of repeated intravenous infusions of an antitumor necrosis factor alpha monoclonal antibody, infliximab, in persistently active, refractory juvenile idiopathic arthritis: results of an open-label prospective study. Arthritis Rheum. 2005;52(2):548-53.

Ruperto N, Lovell DJ, Cuttica R, et al. A randomized, placebo-controlled trial of infliximab plus methotrexate for treatment of polyarticular-course juvenile rheumatoid arthritis. Arthritis Rheum. 2007; 56:3096-106.

Ruperto N, Lovell DJ, Cuttica R, et al. Paediatric Rheumatology INternational Trials Organization (PRINTO); Pediatric Rheumatology Collaborative Study Group (PRCSG). Long-term efficacy and safety of infliximab plus methotrexate for the treatment of polyarticular-course juvenile rheumatoid arthritis: Findings from an open-label treatment extension. Ann Rheum Dis. 2010;69(4):718-722.

Tynjälä P, Vähäsalo P, Tarkiainen M, et al. Aggressive combination drug therapy in very early polyarticular juvenile idiopathic arthritis (ACUTE-JIA): a multicentre randomised open-label clinical trial. Ann Rheum Dis. 2011;70(9):1605-12. Epub 2011 May 28.

3Brooklyn TN, Dunnill MG, Shetty A, Bowden JJ, Williams JD, Griffiths CE, Forbes A, Greenwood R, Probert CS. Infliximab for the treatment of pyoderma gangrenosum: a randomised, double blind, placebo controlled trial. Gut. 2006 Apr;55(4):505-9.

Lexi-Drugs Compendium. Infliximab: Pyoderma Gangrenosum. [Lexicomp Online Web site]. 11/20/14. Available at: http://online.lexi.com/lco/action/doc/retrieve/docid/1150/5256085 [via subscription only]. Accessed January 31, 2017.

Regueiro M, Valentine J, Plevy S, Fleisher MR, Lichtenstein GR. Infliximab for treatment of pyoderma gangrenosum associated with inflammatory bowel disease. Am J Gastroenterol. 2003 Aug;98(8):1821-6.

Schadt C. Pyoderma Gangrenosum: treatment and prognosis. 12/22/16. Available at: https://www.uptodate.com/contents/pyoderma-gangrenosum-treatment-and-prognosis?source=search_result&search=Pyoderma%20gangrenosum&selectedTitle=2~71#H1797000 [via subscription only]. Accessed January 31, 2017.

4Baughman RP, Drent M, Kavuru M et al. Infliximab therapy in patients with chronic sarcoidosis and pulmonary involvement. Am J Respir Crit Care Med. 2006; 174:795-802.

Doty JD, Mazur JE, & Judson MA: Treatment of sarcoidosis with infliximab. Chest 2005; 127(3):1064-1071.

Judson MA, Baughman RP, Costabel U, Flavin S, Lo KH, Kavuru MS, Drent M; Centocor T48 Sarcoidosis Investigators. Efficacy of infliximab in extrapulmonary sarcoidosis: results from a randomised trial. Eur Respir J. 2008;31(6):1189-96.

King TE. Treatment of pulmonary sarcoidosis: Disease refractory to glucocorticoid therapy. last updated: Jan 25, 2017. UpToDate Web Site. Available at: https://www.uptodate.com/contents/treatment-of-pulmonary-sarcoidosis-disease-refractory-to-glucocorticoid-therapy?source=search_result&search=sarcoidosis%20treatment&selectedTitle=2~150 . Accessed February 10, 2017.

Rossman MD, Newman LS, Baughman RP et al. A double-blind, randomized placebo-controled trial of inflximab in patients with active pulmonary sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2006;23:201-208.

5Ellman MH, Hanauer S, Sitrin M, et al. Crohn's disease arthritis treated with infliximab: an open trial in four patients. J Clin Rheumatol. 2001;7:67-71.

Podswiadek M, D'Incà R, Sturniolo GC, Oliviero F, Punzi L. Rheumatic Manifestations Associated with Inflammatory Bowel Diseases. Current Rheumatology Reviews. 2007;3(1):47-56.

Van Den Bosch F, Kruithof E, Baeten D, et al. Randomized double-blind comparison of chimeric monoclonal antibody to tumor necrosis factor alpha (infliximab) versus placebo in active spondylarthropathy. Arthritis Rheum. 2002;46(3):755-765.

6de Carvalho JF, Ribeiro AC, de Moraes JC, Gonçalves C, Goldenstein-Schainberg C, Bonfá E. Infliximab: a promising alternative therapy for refractory arthritis/urethritis/conjunctivitis triad. Isr Med Assoc J. 2009 Aug;11(8):511-3.

Gill H, Majitha V. Successful use of infliximab in the treatment of Reiter's syndrome: a case report and discussion. Clin Rheumatol. 2008; 27:121-123.

Gaylis N. Infliximab in the treatment of an HIV positive patient with Reiter's sydrome. J Rheumatol. 2003;30:407-411.

Oili KS, Niinisalo H, Korpilahde T, et al. Treatment of reactive arthritis with infliximab. Scand J Rheumatol. 2003; 32:122-24.

Schafranski MD. Infliximab for reactive arthritis secondary to Chlamydia trachomatis infection. Rheumatol Int. 2010 Mar;30(5):679-80.

Yu D. Reactive arthritis. 07/21/16. Available at: https://www.uptodate.com/contents/reactive-arthritis?source=search_result&search=spondyloarthritis&selectedTitle=7~150#H28 (via subscription only). Accessed January 23, 2017.

7 Bartolucci P, Ramanoelina J, Cohen P, et al: Efficacy of the anti-TNF-alpha antibody infliximab against refractory systemic vasculitides: an open pilot study on 10 patients. Rheumatology 2002; 41:1126-1132.

de Menthon M, Cohen P, Pagnoux C, et al. Infliximab or rituximab for refractory Wegener's granulomatosis: long-term follow up. A prospective randomised multicentre study on 17 patients. Clin Exp Rheumatol. 2011 Jan-Feb;29(1 Suppl 64):S63-71. Epub 2011 May 11.

Kleinert J., Lorenz M., Kostler W., et al: Refractory Wegener's granulomatosis responds to tumor necrosis factor blockade. Wien Klin Wochenschr 2004; 116(9-10):334-338.

Lamprecht P, Voswinkel J, Lilienthal T, et al: Effectiveness of TNF-alpha blockade with infliximab in refractory Wegener's granulomatosis. Rheumatology (Oxford) 2002; 41(11):1303-1307.

Truven Health Analytics. DrugDex®. infliximab. 10/20/15. [Micromedex® Solutions Web site]. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed November 2, 2015.

8 Menter A, Feldman SR, Weinstein GD, et al. A randomized comparison of continuous vs. intermittent infliximab maintenance regimens over 1 year in the treatment of moderate-to-severe plaque psoriasis. J Am Acad Dermatol. 2007 Jan;56(1):31.e1-15.

Reich K, Nestle FO, Papp K, Ortonne JP, Evans R, Guzzo C, Li S, Dooley LT, Griffiths CE; EXPRESS study investigators. Infliximab induction and maintenance therapy for moderate-to-severe psoriasis: a phase III, multicentre, double-blind trial. Lancet. 2005 Oct 15-21;366(9494):1367-74.

9 Cantini F, Niccoli L, Nannini C, et al. Efficacy of infliximab in refractory Behçet's disease-associated and idiopathic posterior segment uveitis: a prospective, follow-up study of 50 patients. Biologics. 2012;6:5-12.

Elsevier's Clinical Pharmacology Compendium. infliximab. [Clinical Pharmacology Web site]. 09/21/17. Available at: https://www.clinicalkey.com/pharmacology/monograph/2284?sec=monindi&n=Remicade [via subscription only]. Accessed October 2, 2017.

Gallagher M, Quinones K, Cervantes-Castaneda RA, et al. Biological response modifier therapy for refractory childhood uveitis. Br J Ophthalmol. 2007; 91(10):1341-1344.

Rajaraman RT, Kimura Y, Li S, Haines K, Chu DS. Retrospective case review of pediatric patients with uveitis treated with infliximab. Ophthalmology. 2006 Feb;113(2):308-14.

Saurenmann RK, Levin AV, Rose JB, et al. Tumour necrosis factor alpha inhibitors in the treatment of childhood uveitis. Rheumatology (Oxford). 2006 Aug;45(8):982-9.

Simonini G, Zannin ME, Caputo R, et al. Loss of efficacy during long-term infliximab therapy for sight-threatening childhood uveitis. Rheumatology (Oxford). 2008 Oct;47(10):1510-4.

Tynjala P, Lindahl P, Honkanen V, et al. Infliximab and etanercept in the treatment of chronic uveitis associated with refractory juvenile idiopathic arthritis. Ann Rheum Dis. 2007; 66(4):548-550.




Version Effective Date: 04/22/2019
Version Issued Date: 04/22/2019
Version Reissued Date: N/A

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