Milestones in the research, development, and therapeutic use of infliximab

Czech version

Authors: K. Urbánek
Authors‘ workplace: Ústav farmakologie LF UP a FN Olomouc
Published in: Gastroent Hepatol 2026; 80(2): 161-169
Category:
doi: https://doi.org/10.48095/ccgh2026161

Overview

The chimeric monoclonal antibody against tumour necrosis factor (TNF), for which we now use the generic name infliximab, was developed by J. Le and J. Vilček at New York University School of Medicine in collaboration with Centocor (later Janssen Biotech) under the name cA2. In 1992, M. Feldmann and R. Maini used it in the first proof-of-concept study in rheumatoid arthritis to prove the hypothesis that TNF is at the top of the inflammatory cascade of autoimmune inflammation. In 1998, the US FDA approved it under the trade name Remicade for the treatment of Crohn‘s disease. Between 1999 and 2006, it was registered for the treatment of several other autoimmune diseases. The first biologically similar medicinal product (biosimilar) was registered in 2014 under the name CT-P13, which was developed by Celltrion. Infliximab has significantly advanced the pharmacotherapy options for autoimmune diseases, but it has also contributed to the study of their pathophysiology and to the advancement of biological treatment in general.

Keywords:

infliximab – research and development – indications – clinical trials – biosimilars

Sources

1. van Loo G, Bertrand MJM. Death by TNF: a road to inflammation. Nat Rev Immunol 2023; 23(5): 289 –⁠ 303. doi: 10.1038/ s41577-022-00792-3.

2. Carswell EA, Old LJ, Kassel RL et al. An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci U S A 1975; 72(9): 3666 –⁠ 3670. doi: 10.1073/ pnas.72.
9.3666.

3. Beutler B, Greenwald D, Hulmes JD et al. Identity of tumour necrosis factor and the macrophage-secreted factor cachectin. Nature 1985; 316(6028): 552 –⁠ 554. doi: 10.1038/ 316552a0.

4. Dayer JM, Beutler B, Cerami A. Cachectin/
tumor necrosis factor stimulates collagenase and prostaglandin E2 production by human synovial cells and dermal fibroblasts. J Exp Med 1985; 162(6): 2163 –⁠ 2168. doi: 10.1084/ jem.162.6.2163.

5. Riechmann L, Clark M, Waldmann H et al. Reshaping human antibodies for therapy. Nature 1988; 332(6162): 323 –⁠ 327. doi: 10.1038/ 332 323a0.

6. Nadler LM, Roberts WC. Lee Marshall Nadler, MD: a conversation with the editor. Proc (Bayl Univ Med Cent) 2007; 20(4): 381 –⁠ 389. doi: 10.1080/ 08998280.2007.11928327.

7. Smith SL. Ten years of Orthoclone OKT3 (muromonab-CD3): a review. J Transpl Coord 1996; 6(3): 109 –⁠ 119. doi: 10.7182/ prtr.1.6.3.8145 l3u185493182.

8. Reichert JM. Monoclonal antibodies in the clinic. Nat Biotechnol 2001; 19(9): 819 –⁠ 822. doi: 10.1038/ nbt0901-819.

9. Knight DM, Trinh H, Le J et al. Construction and initial characterization of a mouse-human chimeric anti-TNF antibody. Mol Immunol 1993; 30(16): 1443 –⁠ 1453. doi: 10.1016/ 0161-5890(93)90106 -⁠ l.

10. Vilcek J, Feldmann M. Historical review: cytokines as therapeutics and targets of therapeutics. Trends Pharmacol Sci 2004; 25(4): 201 –⁠ 209. doi: 10.1016/ j. tips.2004.02.011.

11. Melsheimer R, Geldhof A, Apaolaza I et al. Remicade (infliximab): 20 years of contributions to science and medicine. Biologics 2019; 13 : 139 –⁠ 178. doi: 10.2147/ BTT.S
207246.

12. Monaco C, Nanchahal J, Taylor P et al. Anti-TNF therapy: past, present and future. Int Immunol 2015; 27(1): 55 –⁠ 62. doi: 10.1093/ intimm/
dxu102.

13. Elliott MJ, Maini RN, Feldmann M et al. Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to tumor necrosis factor alpha. Arthritis Rheum 1993; 36(12): 1681 –⁠ 1690. doi: 10.1002/ art.1780361206.

14. Maini RN, Breedveld FC, Kalden JR et al. Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis. Arthritis Rheum 1998; 41(9): 1552 –⁠ 1563. doi: 10.1002/ 1529-0131(199809)41 : 9<1552::AID-ART5>3.0.CO;2-W.

15. Derkx B, Taminiau J, Radema S et al. Tumour-necrosis-factor antibody treatment in Crohn‘s disease. Lancet 1993; 342(8864): 173 –⁠ 174. doi: 10.1016/ 0140-6736(93)91375-v.

16. van Dullemen HM, van Deventer SJ, Hommes DW et al. Treatment of Crohn‘s disease with anti-tumor necrosis factor chimeric monoclonal antibody (cA2). Gastroenterology 1995; 109(1): 129 –⁠ 135. doi: 10.1016/ 0016-5085(95)
90277-5.

17. Targan SR, Hanauer SB, van Deventer SJ et al. A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn‘s disease. Crohn‘s disease cA2 study group. N Engl J Med 1997; 337(15): 1029 –⁠ 1035. doi: 10.1056/ NEJM199710093371502.

18. Present DH, Rutgeerts P, Targan S et al. Infliximab for the treatment of fistulas in patients with Crohn‘s disease. N Engl J Med 1999; 340(18): 1398 –⁠ 1405. doi: 10.1056/ NEJM 199905063401804.

19. Maini R, St Clair EW, Breedveld F et al. Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. ATTRACT Study Group. Lancet 1999; 354(9194): 1932 –⁠ 1939. doi: 10.1016/ s0140-
6736(99)05246-0.

20. Hanauer SB, Feagan BG, Lichtenstein GR
et al. Maintenance infliximab for Crohn‘s disease: the ACCENT I randomised trial. Lancet 2002; 359(9317): 1541 –⁠ 1549. doi: 10.1016/ S0140-6736(02)08512-4.

21. Sands BE, Anderson FH, Bernstein CN et al. Infliximab maintenance therapy for fistulizing Crohn‘s disease. N Engl J Med 2004; 350(9): 876 –⁠ 885. doi: 10.1056/ NEJMoa030815.

22. Braun J, Brandt J, Listing J et al. Treatment of active ankylosing spondylitis with infliximab: a randomised controlled multicentre trial. Lancet 2002; 359(9313): 1187 –⁠ 1193. doi: 10.1016/ s0140-6736(02)08215-6.

23. van der Heijde D, Dijkmans B, Geusens P et al. Efficacy and safety of infliximab in patients with ankylosing spondylitis: results of a randomized, placebo-controlled trial (ASSERT). Arthritis Rheum 2005; 52(2): 582 –⁠ 591. doi: 10.1002/ art.20852.

24. Rutgeerts P, Sandborn WJ, Feagan BG et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med 2005; 353(23): 2462 –⁠ 2476. doi: 10.1056/ NEJMoa
050516.

25. Antoni C, Krueger GG, de Vlam K et al. Infliximab improves signs and symptoms of psoriatic arthritis: results of the IMPACT 2 trial. Ann Rheum Dis 2005; 64(8): 1150 –⁠ 1157. doi: 10.1136/ ard.2004.032268.

26. Reich K, Nestle FO, Papp K et al. Infliximab induction and maintenance therapy for moderate-to-severe psoriasis: a phase III, multicentre, double-blind trial. Lancet 2005; 366(9494): 1367 –⁠ 1374. doi: 10.1016/ S0140-6736(05) 67566-6.

27. Grimstad Ø. Tumor necrosis factor and the tenacious a. JAMA Dermatol 2016; 152(5): 557. doi: 10.1001/ jamadermatol.2015.4322.

28. Papadakis KA, Targan SR. Tumor necrosis factor: biology and therapeutic inhibitors. Gastroenterology 2000; 119(4): 1148 –⁠ 1157. doi: 10.1053/ gast.2000.18160.

29. Falvo JV, Tsytsykova AV, Goldfeld AE. Transcriptional control of the TNF gene. Curr Dir Autoimmun 2010; 11 : 27 –⁠ 60. doi: 10.1159/ 000289196.

30. Horiuchi T, Mitoma H, Harashima S et al. Transmembrane TNF-alpha: structure, function and interaction with anti-TNF agents. Rheumatology (Oxford) 2010; 49(7): 1215 –⁠ 1228. doi: 10.1093/ rheumatology/ keq031.

31. van Loo G, Bertrand MJM. Death by TNF: a road to inflammation. Nat Rev Immunol 2023; 23(5): 289 –⁠ 303. doi: 10.1038/ s41577-022-
00792-3.

32. Rahman MU, Strusberg I, Geusens P et al. Double-blinded infliximab dose escalation in patients with rheumatoid arthritis. Ann Rheum Dis 2007; 66(9): 1233 –⁠ 1238. doi: 10.1136/ ard.2006.065995.

33. Maser EA, Villela R, Silverberg MS et al. Association of trough serum infliximab to clinical outcome after scheduled maintenance treatment for Crohn‘s disease. Clin Gastroenterol Hepatol 2006; 4(10): 1248 –⁠ 1254. doi: 10.1016/ j. cgh.2006.06.025.

34. Ordás I, Mould DR, Feagan BG et al. Anti-TNF monoclonal antibodies in inflammatory bowel disease: pharmacokinetics-based dosing paradigms. Clin Pharmacol Ther 2012; 91(4): 635 –⁠ 646. doi: 10.1038/ clpt.2011.328.

35. Feuerstein JD, Nguyen GC, Kupfer SS et al. American Gastroenterological Association Institute Guideline on therapeutic drug monitoring in inflammatory bowel disease. Gastroenterology 2017; 153(3): 827 –⁠ 834. doi: 10.1053/ j. gastro.2017.07.032.

36. Urbánek K. První biosimilární monoklonální protilátka –⁠ infliximab. Klin Farmakol Farm 2014; 28(1): 19 –⁠ 22.

37. Jørgensen KK, Olsen IC, Goll GL et al. Switching from originator infliximab to biosimilar
CT-P13 compared with maintained treatment with originator infliximab (NOR-SWITCH):
a 52-week, randomised, double-blind, non-inferiority trial. Lancet 2017; 389(10086): 2304 –⁠ 2316. doi: 10.1016/ S0140-6736(17)30068-5.

38. Iannone F, Conti F, Cauli A et al. Subcutaneously-administered infliximab in the management of rheumatoid arthritis: a short narrative review of current clinical evidence. J Inflamm Res 2022; 15 : 3259 –⁠ 3267. doi: 10.2147/ JIR.240593.

39. Westhovens R, Wiland P, Zawadzki M et al. Efficacy, pharmacokinetics and safety of subcutaneous versus intravenous CT-P13 in rheumatoid arthritis: a randomized phase I/ III trial. Rheumatology (Oxford) 2021; 60(5): 2277 –⁠ 2287. doi: 10.1093/ rheumatology/ keaa580.

40. Nam K, Kwon TS, Di Biasio F et al. Perceived benefits and cost savings of liquid formulation of intravenous infliximab: perspectives of seven European countries. Expert Opin Biol Ther 2025; 25(9): 1017 –⁠ 1024. doi: 10.1080/ 14712598.2025.2544756.