DOSING AND FREQUENCY REQUIREMENTS FOR INTRAVENOUS INFLIXIMAB (REMICADE) AND RELATED BIOSIMILARS (E.G., UNBRANDED INFLIXIMAB, INFLIXIMAB-ABDA [RENFLEXIS], INFLIXIMAB-AXXQ [AVSOLA], INFLIXIMAB-DYYB [INFLECTRA], 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 (i.e., 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 |
Acute graft-versus-host disease (aGVHD) 10
| Infliximab 10 mg/kg IV weekly for a maximum of 9 doses
|
| Anklyosing spondylitis and Nonradiographic Axial Spondyloarthritis 1 | Induction: 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) |
Behcet's syndrome 13
| Induction: 5 mg/kg IV at weeks 0, 2, and 6
Maintenance: 5 mg/kg IV every 6-8 weeks (up to a maximum of 10 mg/kg IV every 8 weeks)
|
Crohn's disease (moderate to severe) or fistulizing Crohn's disease1, 7
| Adults:
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 10 mg/kg and/or decreasing the interval between infusions to 4-6 weeks.
|
Hidradenitis Suppurativa 11
| Induction: 5-10 mg/kg IV at weeks 0, 2, and 6
Maintenance: 5-10 mg/kg IV every 4 weeks, and with decreasing dosage as tolerated. |
Toxicities Related to Immune Checkpoint Inhibitors 12
| Infliximab 5 mg/kg IV at weeks 0, 2, and 6 |
| 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) 2 | Induction: 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 arthritis1 | 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) |
| 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 arthritis1 | Induction: 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 gangrenosum3 | Induction: 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 4
| Induction: 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)1, 14 | 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)
- 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 |
REFERENCES
1 Remicade (Infliximab) [package insert]. Horsham, PA. Janssen Biotech. Revised 10/2021. Available at: http://www.remicade.com/. Accessed December 13, 2023.
Unbranded infliximab [package insert]. Horsham, PA. Janssen Biotech. 10/2021. Available at: https://www.infliximab.com/. Accessed December 13, 2023.
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):718-22.
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.
3 Brooklyn TN, Dunnill MG, Shetty A, et al. 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. [Lexicomp Online Web site]. 12/22/2023. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed December 26, 2023.
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. [UpToDate Web Site]. 12/04/2023. Available at: https://www.uptodate.com/contents/pyoderma-gangrenosum-treatment-and-prognosis?source=search_result&search=Pyoderma gangrenosum&selectedTitle=2~71#H1797000 [via subscription only]. Accessed December 19, 2023.
4 Baughman 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.
Baughman RP, Valeyre D,
Korsten P, et al. ERS clinical practice guidelines on treatment of
sarcoidosis. Eur Respir J. 2021;58(6):2004079.
Doty JD, Mazur JE, & Judson MA: Treatment of sarcoidosis with infliximab. Chest 2005; 127(3):1064-1071.
Judson MA, Baughman RP, Costabel U, et al; Centocor T48 Sarcoidosis Investigators. Efficacy of infliximab in extrapulmonary sarcoidosis: results from a randomised trial. Eur Respir J. 2008;31(6):1189-96.
Sakkat A, Cox G, Khalidi N, et al. Infliximab therapy in refractory sarcoidosis: a multicenter real-world analysis. Respir Res. 2022;23(1):54.
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.
5 Ellman 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.
Inman RD. Treatment of arthritis associated with inflammatory bowel disease. 03/11/2022. [UpTo Date Website]. Available at: https://www.uptodate.com/contents/treatment-of-arthritis-associated-with-inflammatory-bowel-disease?search=spondyloarthritis&topicRef=7787&source=see_link [via subscription only]. Accessed December 26, 2023.
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.
6 de 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; 27:121-3.
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;30(5):679-80.
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 Atienza-Mateo B, Martin-Varillas JL, Calvo-Rio V, et al. Comparative
Study of Infliximab Versus Adalimumab in Refractory Uveitis due to Behcet's
Disease: National Multicenter Study of 177 Cases. Arthritis Rheumatol. Dec
2019; 71(12): 2081-2089.
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]. 12/27/2023. Available at: https://www.clinicalkey.com/pharmacology/monograph/2284?sec=monindi [via subscription only]. Accessed December 26, 2023.
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.
Kunimi K, Usui Y, Asakage M, et al. Anti-TNF- Therapy for Refractory Uveitis Associated with Behcet's Syndrome and Sarcoidosis: A Single Center Study of 131 Patients. Ocul Immunol Inflamm. Aug 20 2020: 1-8.
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.
10 Couriel D, Saliba R, Hicks K, et al. Tumor necrosis factor-alpha blockade for the treatment of acute GVHD. Blood. 2004;104(3):649-54.
Kobbe G, Schneider P, Rohr U, et al. Treatment of
severe steroid refractory acute graft-versus-host disease with infliximab, a
chimeric human/mouse antiTNF alpha antibody. Bone Marrow Transplant . 2001;28:47-49.
National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Hematopoietic Cell Transplantation. v.3.2023. [NCCN Web site]. 10/09/2023. Available at: https://www.nccn.org/store/login/login.aspx?ReturnURL=https://www.nccn.org/professionals/physician_gls/pdf/hct.pdf [via subscription only]. Accessed December 19, 2023.
Patriarca F, Sperotto A, Damiani D, et al. Infliximab treatment for steroid-refractory acute graft-versus-host disease. Haematologica. 2004;89(11):1352-9.
Yalniz FF, Hefazi M, McCullough K, et al. Safety and Efficacy of Infliximab Therapy in the Setting of Steroid-Refractory Acute Graft-versus-Host Disease. Biol Blood Marrow Transplant. 2017;23(9):1478-1484.
11 Alikhan A, Sayed C, Alavi A, et al. North American clinical management guidelines for hidradenitis suppurativa: A publication from the United States and Canadian Hidradenitis Suppurativa Foundations: Part II: Topical, intralesional, and systemic medical management. J Am Acad Dermatol. 2019 Jul;81(1):91-101.
Ghias MH, Johnston AD, Kutner AJ, Micheletti RG, Hosgood HD, Cohen SR. High-dose, high-frequency infliximab: A novel treatment paradigm for hidradenitis suppurativa. J Am Acad Dermatol. 2020 May;82(5):1094-1101.
Lesage C, Adnot-Desanlis L, Perceau G, et al. Efficacy and tolerance of prolonged infliximab treatment of moderate-to-severe forms of hidradenitis suppurativa. Eur J Dermatol. 2012 Sep-Oct;22(5):640-4.
Moriarty B, Jiyad Z, Creamer D. Four-weekly infliximab
in the treatment of severe hidradenitis suppurativa. Br J Dermatol. 2014
Apr;170(4):986-7.
12 Brahmer JR, Lacchetti C, Schneider BJ, et al; National Comprehensive Cancer Network. 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(17):1714-1768.
13 Giardina A, Ferrante A, Ciccia F, et al. One year study of efficacy and safety of infliximab in the treatment of patients with ocular and neurological Behcet's disease refractory to standard immunosuppressive drugs. Rheumatol Int 2011;31:33-7.
Hibi T, Hirohata S, Kikuchi H, et al. Infliximab therapy for intestinal, neurological, and vascular involvement in Behcet disease: Efficacy, safety, and pharmacokinetics in a multicenter, prospective, open-label, single-arm phase 3 study. Medicine (Baltimore). Jun 2016; 95(24): e3863.
Robertson LP, Hickling P. Treatment of recalcitrant orogenital ulceration of Behcet's syndrome with infliximab. Rheumatology. 2001; 40:473-4.
Smith EL, Yazici Y. Treatment of Behçet syndrome. 08/15/2022. Available at: https://www.uptodate.com/contents/treatment-of-behcet-syndrome?search=behcet treatment&source=search_result&selectedTitle=1~129&usage_type=default&display_rank=1. Accessed December 19, 2023.
14 Brandse JF, van den Brink GR, Wildenberg ME, et al. Loss of infliximab into feces is associated with lack of response to therapy in patients with severe ulcerative colitis. Gastroenterology. 2015;149(2):350-355.
Church PC, Ho S, Sharma A, et al. Intensified infliximab induction is associated with improved response and decreased colectomy in steroid-refractory paediatric ulcerative colitis. J Crohns Colitis. 2019;13(8):982-9.
Turner D, Ruemmele FM, Orlanski-Meyer E, et al. Management of Pediatric Ulcerative Colitis, Part 1: Ambulatory Care-An Evidence-based Guideline From European Crohn's and Colitis Organization and European Society of Paediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 2018;67(2):257-91.
Turner D, Ruemmele FM, Orlanski-Meyer E, et al. Management of Pediatric Ulcerative Colitis, Part 2: Ambulatory Care-An Evidence-based Guideline From European Crohn's and Colitis Organization and European Society of Paediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 2018;67(2):292-310.
