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infliximab (Remicade)

Biosimilars: - FDA-approved April 2016 infliximab-dyyb (Inflectra) [11] - FDA-approved April 2017 infliximab-abda (Renflexis) [12] Indications: - Crohn's disease, ulcerative colitis [4,6,7,8] - rheumatoid arthritis [8] - severe psoriasis refractory to standard therapy [6] - psoriatic arthritis [8] - ankylosing spondylitis [8] - subcorneal pustular dermatosis [9] Contraindications: 1) hypersensitivity to murine proteins 2) discontinue use in patients with serious infections or sepsis 3) do not initiate therapy in patients with active infections, including chronic or localized infections* 4) heart failure [3] 5) concurrent use of other biologic agent (abatacept, rituximab, anakinra, other TNF inhibitor) * Screening for tuberculosis recommended prior to initiating therapy Pregnancy category: B [8] Precautions: - may exacerbate multiple sclerosis Dose: 1) Crohn's disease: a) 5 mg/kg IV b) additional doses at 2 & 6 weeks after initial dose 2) rheumatoid arthritis a) 10 mg/kg IV b) used in combination with methotrexate c) additional infusion(s) 6-12 weeks after initial infusion 3) IV infusion over 2 hours 4) normal saline is used as a diluent Store lyophylized at 2-8 degrees C Monitor: - screening for tuberculosis [8] - CBC, LFTs, serum creatinine at baseline & every 2-3 months thereafter [8] Pharmacokinetics: 1) maximum concentration of 118 ug/mL 2) median volume of distribution: 3 liters - corticosteroid use increases volume of distribution from 2.8-3.3 liters 3) terminal 1/2life of 9.5 days Adverse effects: 1) infusion-related reactions: a) fever/chills b) pruritus/urticaria c) chest d) hypertension or hypotension e) dyspnea f) edema/weight gain g) headache h) nausea 2) may increase risk of tuberculosis [2] 3) may worsen heart failure [3] 4) may increase risk of serious infections [5,10] - no increase in infections when given within 4 weeks of hip replacement or knee replacement [14] 5) may increase risk of malignancy [5] - non-Hodgkin's lymphoma [8] 6) drug-induced lupus erythematosus [8] 7) serum sickness-like reaction to murine light & heavy chain variable regions Drug interactions: - recommended that live vaccines NOT be given concurrently Laboratory: - infliximab in serum/plasma - infliximab Ab in serum/plasma Mechanism of action: 1) chimeric (mouse-human) monoclonal antibody to TNF-alpha (partially humanized mouse monoclonal Ab) [8] 2) binds to both transmembrane & soluble TNF-alpha 3) inhibits binding of TNF-alpha to TNFRSF1A/TNFRSF1B TNF receptors Notes: - 2017 Medicare part D cost: $17,335/year, out of pocket $3432 [15]

Interactions

drug adverse effects of immunosuppressive agents monitor with immunosuppressive agents

Related

tumor necrosis factor [TNF]-alpha; tumor necrosis factor ligand superfamily member 2; cachectin (TNF, TNFA, TNFSF2)

Specific

infliximab-abda (Renflexis) infliximab-dyyb (Inflectra, Remisima, CT-P13)

General

recombinant protein; chimer pharmaceutical monoclonal antibody tumor necrosis factor (TNF) inhibitor

References

  1. DrugDex Drug Evaluation, 2000
  2. Prescriber's Letter 8(10):58 2001
  3. Prescriber's Letter 10(7):39 2003
  4. Prescriber's Letter 12(9): 2005 Drug Therapy for Ulcerative colitis Detail-Document#: 211112 (subscription needed) http://www.prescribersletter.com
  5. Prescriber's Letter 13(7): 2006 Safety Concerns of Anti-TNF Antibody Therapy Detail-Document#: 220711 (subscription needed) http://www.prescribersletter.com
  6. Fidder H et al. Long-term safety of infliximab for the treatment of inflammatory bowel disease: A single-centre cohort study. Gut 2009 Apr; 58:501. PMID: 18832524
  7. FDA NEWS RELEASE: Sept. 23, 2011 FDA approves Remicade to treat ulcerative colitis in children older than 6 years http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm272997.htm
  8. Medical Knowledge Self Assessment Program (MKSAP) 16, 17, 18, 19. American College of Physicians, Philadelphia 2012, 2015, 2018, 2022
  9. Deprecated Reference
  10. Kalb RE, Fiorentino DF, Lebwohl MG et al Risk of Serious Infection With Biologic and Systemic Treatment of Psoriasis: Results From the Psoriasis Longitudinal Assessment and Registry (PSOLAR). JAMA Dermatol. 2015 May 13 PMID: 25970800
  11. FDA News Release. April 5, 2016 FDA approves Inflectra, a biosimilar to Remicade http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm494227.htm
  12. Brooks M FDA Clears Second Remicade Biosimilar (Renflexis) Medscape. April 21, 2017 http://www.medscape.com/viewarticle/878963
  13. Keane J, Gershon S, Wise RP et al Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med. 2001 Oct 11;345(15):1098-104. PMID: 11596589 Free Article http://www.nejm.org/doi/full/10.1056/NEJMoa011110
  14. George MD, Baker JF, Hsu JY et al. Perioperative timing of infliximab and the risk of serious infection after elective hip and knee arthroplasty. Arthritis Care Res (Hoboken) 2017 Dec; 69:1845 PMID: 28129484 http://onlinelibrary.wiley.com/doi/10.1002/acr.23209/abstract
  15. Yazdany J, Dudley RA, Lin GA et al Out-of-Pocket Costs for Infliximab and Its Biosimilar for Rheumatoid Arthritis Under Medicare Part D. JAMA. 2018;320(9):931-933 PMID: 30193264 https://jamanetwork.com/journals/jama/fullarticle/2698912