OBJECTIVE: The adalimumab biosimilars FKB327 and GP2017 were approved for the therapy of patients with inflammatory bowel disease (IBD). Relatively few prospective studies with biosimilar adalimumab in patients with IBD have been published. The aim of this prospective observational study was to evaluate the effectiveness and safety of the biosimilar adalimumab. MATERIAL AND METHODS: Adalimumab biosimilars FKB327 (Hulio®) and GP2017 (Hyrimoz®) were indicated to 50 naive patients in terms of biological therapy with Crohn's disease (CD) or ulcerative colitis (UC). Effectiveness of therapy was evaluated via the Crohn's Disease Activity Index [CDAI] or the Mayo Scoring System [MSS] in patients with CD or UC, respectively, before and after 12 weeks. Additional goals were to evaluate weight changes, laboratory tests and complications or adverse events of this therapy. RESULTS: In CD patients, remission (CDAI <150) was achieved in 73.5% of cases, partial response (≥70-point decrease in CDAI score from baseline) in 11.8%, no response in 11.8% and 2.9% patients discontinued therapy. In UC patients, remission (total score on partial Mayo index ≤2 points) was achieved only in 18.8% of cases, partial response (≥2-point decrease in partial Mayo score from baseline) in 43.8%, no response in 25.0% and 12.5% patients discontinued therapy. There were statistically significant improvements in CDAI, MSS, haemoglobin, fecal calprotectin, albumin and CRP serum levels after 12 weeks of therapy. Seven adverse events were identified, three of which resulted in therapy being discontinued. CONCLUSIONS: This prospective observational study proved the effectiveness of the adalimumab biosimilars FKB327 and GP2017 in IBD.

2nd Department of Internal Medicine 3rd Faculty of Medicine FNKV Charles University Prague Prague Czech Republic

2nd Department of Internal Medicine University Hospital Plzeň Bory Plzeň Czech Republic

Department for the Treatment of Non specific Intestinal Inflammations IBD Center Turnov Hospital Turnov Turnov Czech Republic

Department of Internal Medicine 1st Faculty of Medicine Military University Hospital Charles University Prague Prague Czech Republic

Department of Internal Medicine 2nd Faculty of Medicine Motol University Hospital Charles University Prague Prague Czech Republic

Department of Internal Medicine and Gastroenterology Faculty of Medicine University Hospital Brno Masaryk University Brno Czech Republic

Department of Internal Medicine Regional Hospital of T Baťa Zlín Czech Republic

Department of Pediatric Surgery 2nd Faculty of Medicine University Hospital Motol Charles University Prague Prague Czech Republic

Laboratory of Cellular and Molecular Immunology Institute of Microbiology of the Czech Academy of Sciences Prague Czech Republic

Zobrazit více v PubMed

Podolsky DK, Camilleri M, Fitz JG, Kalloo AN, Shanahan F, Wang TC et al.. Yamada´s Textbook of Gastroenterology, 6th edition, John Wiley & Sons, New Jersey, 2016; 1364–1377

Feldman M, Friedman L, Brandt L, Chung RT, Rubin DT, Wilcox CM et al.. Sleisenger and Fordtran’s gastrointestinal and liver disease: pathophysiology, diagnosis, management, 11th edition. Elsevier, Philadelphia: 2016; 1868–1897.

Feagan BG, Panaccione R, Sandborn WJ, D’Haens GR, Schreiber S, Rutgeerts PJ, et al.. Effects of adalimumab therapy on incidence of hospitalization and surgery in Crohn’s disease: results from the CHARM study. Gastroenterology. 2008. Nov;135(5):1493–9. doi: 10.1053/j.gastro.2008.07.069 Epub 2008 Aug 3. . PubMed DOI

Ford AC, Sandborn WJ, Khan KJ, Hanauer SB, Talley NJ, Moayyedi P. Efficacy of biological therapies in inflammatory bowel disease: systematic review and meta-analysis. Am J Gastroenterol. 2011. Apr;106(4):644–59, quiz 660. doi: 10.1038/ajg.2011.73 Epub 2011 Mar 15. . PubMed DOI

Taxonera C, Estellés J, Fernández-Blanco I, Merino O, Marín-Jiménez I, Barreiro-de Acosta M, et al.. Adalimumab induction and maintenance therapy for patients with ulcerative colitis previously treated with infliximab. Aliment Pharmacol Ther. 2011. Feb;33(3):340–8. doi: 10.1111/j.1365-2036.2010.04531.x Epub 2010 Dec 7. . PubMed DOI

Reinisch W, Sandborn WJ, Hommes DW, D’Haens G, Hanauer S, Schreiber S, et al.. Adalimumab for induction of clinical remission in moderately to severely active ulcerative colitis: results of a randomised controlled trial. Gut. 2011. Jun;60(6):780–7. doi: 10.1136/gut.2010.221127 Epub 2011 Jan 5. . PubMed DOI

Chen X, Hou J, Yuan Y, Huang C, Liu T, Mo C, et al.. Adalimumab for Moderately to Severely Active Ulcerative Colitis: A Systematic Review and Meta-Analysis. BioDrugs. 2016. Jun;30(3):207–17. doi: 10.1007/s40259-016-0173-6 . PubMed DOI

Colombel JF, Sandborn WJ, Ghosh S, Wolf DC, Panaccione R, Feagan B, et al.. Four-year maintenance treatment with adalimumab in patients with moderately to severely active ulcerative colitis: Data from ULTRA 1, 2, and 3. Am J Gastroenterol. 2014. Nov;109(11):1771–80. doi: 10.1038/ajg.2014.242 Epub 2014 Aug 26. . PubMed DOI PMC

Declerck P, Danesi R, Petersel D, Jacobs I. The Language of Biosimilars: Clarification, Definitions, and Regulatory Aspects. Drugs. 2017. Apr;77(6):671–677. doi: 10.1007/s40265-017-0717-1 . PubMed DOI PMC

Moorkens E, Vulto AG, Huys I, Dylst P, Godman B, Keuerleber S, et al.. Policies for biosimilar uptake in Europe: An overview. PLoS One. 2017. Dec 28;12(12):e0190147. doi: 10.1371/journal.pone.0190147 . PubMed DOI PMC

Ishii-Watabe A, Kuwabara T. Biosimilarity assessment of biosimilar therapeutic monoclonal antibodies. Drug Metab Pharmacokinet. 2019. Feb;34(1):64–70. doi: 10.1016/j.dmpk.2018.11.004 Epub 2018 Dec 7. . PubMed DOI

Kurki P, van Aerts L, Wolff-Holz E, Giezen T, Skibeli V, Weise M. Interchangeability of Biosimilars: A European Perspective. BioDrugs. 2017. Apr;31(2):83–91. doi: 10.1007/s40259-017-0210-0 . PubMed DOI

Sullivan PM, DiGrazia LM. Analytic characterization of biosimilars. Am J Health Syst Pharm. 2017. Apr 15;74(8):568–579. doi: 10.2146/ajhp150971 . PubMed DOI

Tesser JR, Furst DE, Jacobs I. Biosimilars and the extrapolation of indications for inflammatory conditions. Biologics. 2017. Feb 17;11:5–11. doi: 10.2147/BTT.S124476 . PubMed DOI PMC

Weise M, Kurki P, Wolff-Holz E, Bielsky MC, Schneider CK. Biosimilars: the science of extrapolation. Blood. 2014. Nov 20;124(22):3191–6. doi: 10.1182/blood-2014-06-583617 Epub 2014 Oct 8. . PubMed DOI

Genovese MC, Glover J, Greenwald M, Porawska W, El Khouri EC, Dokoupilova E, et al.. FKB327, an adalimumab biosimilar, versus the reference product: results of a randomized, Phase III, double-blind study, and its open-label extension. Arthritis Res Ther. 2019. Dec 12;21(1):281. doi: 10.1186/s13075-019-2046-0 . PubMed DOI PMC

Blauvelt A, Lacour JP, Fowler JF Jr, Weinberg JM, Gospodinov D, Schuck E, et al.. Phase III randomized study of the proposed adalimumab biosimilar GP2017 in psoriasis: impact of multiple switches. Br J Dermatol. 2018. Sep;179(3):623–631. doi: 10.1111/bjd.16890 Epub 2018 Jul 15. . PubMed DOI

Bortlik M, Ďuricová D, Douda T, Konecný M, Kozeluhová J, Novotný A et al.. Guidelines for the administration of biological therapy in patients with inflammatory bowel diseases: Fourth, updated edition. Gastroenterologie a hepatologie. 2019,73:11–24.

Torres J, Bonovas S, Doherty G, Kucharzik T, Gisbert JP, Raine T, et al.. ECCO Guidelines on Therapeutics in Crohn’s Disease: Medical Treatment. J Crohns Colitis. 2020. Jan 1;14(1):4–22. doi: 10.1093/ecco-jcc/jjz180 . PubMed DOI

Harbord M, Eliakim R, Bettenworth D, Karmiris K, Katsanos K, Kopylov U, et al.. Third European Evidence-based Consensus on Diagnosis and Management of Ulcerative Colitis. Part 2: Current Management. J Crohns Colitis. 2017. Jul 1;11(7):769–784. doi: 10.1093/ecco-jcc/jjx009 Erratum in: J Crohns Colitis. 2017 Dec 4;11(12):1512. . PubMed DOI

Hanauer SB, Sandborn WJ, Rutgeerts P, Fedorak RN, Lukas M, MacIntosh D, et al.. Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn’s disease: the CLASSIC-I trial. Gastroenterology. 2006. Feb;130(2):323–33; quiz 591. doi: 10.1053/j.gastro.2005.11.030 . PubMed DOI

Farkas K, Rutka M, Ferenci T, Nagy F, Bálint A, Bor R, et al.. Infliximab biosimilar CT-P13 therapy is effective and safe in maintaining remission in Crohn’s disease and ulcerative colitis—experiences from a single center. Expert Opin Biol Ther. 2017. Nov;17(11):1325–1332. doi: 10.1080/14712598.2017.1363885 Epub 2017 Aug 18. . PubMed DOI

Keil R, Wasserbauer M, Zádorová Z, Hajer J, Drastich P, Wohl P, et al.. Clinical monitoring: infliximab biosimilar CT-P13 in the treatment of Crohn’s disease and ulcerative colitis. Scand J Gastroenterol. 2016. Sep;51(9):1062–8. doi: 10.3109/00365521.2016.1149883 Epub 2016 Mar 22. . PubMed DOI PMC

Schmitz EMH, Boekema PJ, Straathof JWA, van Renswouw DC, Brunsveld L, Scharnhorst V, et al.. Switching from infliximab innovator to biosimilar in patients with inflammatory bowel disease: a 12-month multicentre observational prospective cohort study. Aliment Pharmacol Ther. 2018. Feb;47(3):356–363. doi: 10.1111/apt.14453 Epub 2017 Dec 5. . PubMed DOI

Kamat N, Kedia S, Ghoshal UC, Nehra A, Makharia G, Sood A, et al.. Effectiveness and safety of adalimumab biosimilar in inflammatory bowel disease: A multicenter study. Indian J Gastroenterol. 2019. Feb;38(1):44–54. doi: 10.1007/s12664-018-0922-1 Epub 2019 Jan 15. . PubMed DOI

Chandra A, Kanth R, Thareja S. Efficacy And Safety Of Adalimumab Biosimilar (Exemptia) In Moderate-To-Severe Steroid-Refractory Ulcerative Colitis Patients: Real-Life Outcomes In Resource-Constrained Setting At 24-Weeks Follow-Up. Biologics. 2019. Nov 25;13:191–200. doi: 10.2147/BTT.S214518 . PubMed DOI PMC

Ribaldone DG, Caviglia GP, Pellicano R, Vernero M, Saracco GM, Morino M, et al.. Effectiveness and safety of adalimumab biosimilar ABP 501 in Crohn’s disease: an observational study. Rev Esp Enferm Dig. 2020. Mar;112(3):195–200. doi: 10.17235/reed.2020.6693/2019 . PubMed DOI

Sturm A, Maaser C, Calabrese E, Annese V, Fiorino G, Kucharzik T, et al.. ECCO-ESGAR Guideline for Diagnostic Assessment in IBD Part 2: IBD scores and general principles and technical aspects. J Crohns Colitis. 2019. Mar 26;13(3):273–284. doi: 10.1093/ecco-jcc/jjy114 . PubMed DOI

Papay P, Ignjatovic A, Karmiris K, Amarante H, Milheller P, Feagan B, et al.. Optimising monitoring in the management of Crohn’s disease: a physician’s perspective. J Crohns Colitis. 2013. Sep;7(8):653–69. doi: 10.1016/j.crohns.2013.02.005 Epub 2013 Apr 4. . PubMed DOI

Sostegni R, Daperno M, Scaglione N, Lavagna A, Rocca R, Pera A. Review article: Crohn’s disease: monitoring disease activity. Aliment Pharmacol Ther. 2003. Jun;17 Suppl 2:11–7. doi: 10.1046/j.1365-2036.17.s2.17.x . PubMed DOI

D’Haens G, Sandborn WJ, Feagan BG, Geboes K, Hanauer SB, Irvine EJ, et al.. A review of activity indices and efficacy end points for clinical trials of medical therapy in adults with ulcerative colitis. Gastroenterology. 2007. Feb;132(2):763–86. doi: 10.1053/j.gastro.2006.12.038 Epub 2006 Dec 20. . PubMed DOI

Mosli MH, Zou G, Garg SK, Feagan SG, MacDonald JK, Chande N, et al.. C-Reactive Protein, Fecal Calprotectin, and Stool Lactoferrin for Detection of Endoscopic Activity in Symptomatic Inflammatory Bowel Disease Patients: A Systematic Review and Meta-Analysis. Am J Gastroenterol. 2015. Jun;110(6):802–19; quiz 820. doi: 10.1038/ajg.2015.120 Epub 2015 May 12. . PubMed DOI

Consigny Y, Modigliani R, Colombel JF, Dupas JL, Lémann M, Mary JY; Groupe d’Etudes Thérapeutiques des Affections Inflammatoires Digestives (GETAID). A simple biological score for predicting low risk of short-term relapse in Crohn’s disease. Inflamm Bowel Dis. 2006. Jul;12(7):551–7. doi: 10.1097/01.ibd.0000225334.60990.5b . PubMed DOI

Roblin X, Marotte H, Leclerc M, Del Tedesco E, Phelip JM, Peyrin-Biroulet L, et al.. Combination of C-reactive protein, infliximab trough levels, and stable but not transient antibodies to infliximab are associated with loss of response to infliximab in inflammatory bowel disease. J Crohns Colitis. 2015. Jul;9(7):525–31. doi: 10.1093/ecco-jcc/jjv061 Epub 2015 Apr 19. . PubMed DOI

Heida A, Park KT, van Rheenen PF. Clinical Utility of Fecal Calprotectin Monitoring in Asymptomatic Patients with Inflammatory Bowel Disease: A Systematic Review and Practical Guide. Inflamm Bowel Dis. 2017. Jun;23(6):894–902. doi: 10.1097/MIB.0000000000001082 . PubMed DOI PMC

Gisbert JP, Bermejo F, Pérez-Calle JL, Taxonera C, Vera I, McNicholl AG, et al.. Fecal calprotectin and lactoferrin for the prediction of inflammatory bowel disease relapse. Inflamm Bowel Dis. 2009. Aug;15(8):1190–8. doi: 10.1002/ibd.20933 . PubMed DOI

Zittan E, Kelly OB, Kirsch R, Milgrom R, Burns J, Nguyen GC, et al.. Low Fecal Calprotectin Correlates with Histological Remission and Mucosal Healing in Ulcerative Colitis and Colonic Crohn’s Disease. Inflamm Bowel Dis. 2016. Mar;22(3):623–30. doi: 10.1097/MIB.0000000000000652 . PubMed DOI

Schoepfer AM, Beglinger C, Straumann A, Safroneeva E, Romero Y, Armstrong D, et al.. Fecal calprotectin more accurately reflects endoscopic activity of ulcerative colitis than the Lichtiger Index, C-reactive protein, platelets, hemoglobin, and blood leukocytes. Inflamm Bowel Dis. 2013. Feb;19(2):332–41. doi: 10.1097/MIB.0b013e3182810066 . PubMed DOI

Rahier JF, Magro F, Abreu C, Armuzzi A, Ben-Horin S, Chowers Y, et al.. Second European evidence-based consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease. J Crohns Colitis. 2014. Jun;8(6):443–68. doi: 10.1016/j.crohns.2013.12.013 Epub 2014 Mar 6. . PubMed DOI

Reddy JG, Loftus EV Jr. Safety of infliximab and other biologic agents in the inflammatory bowel diseases. Gastroenterol Clin North Am. 2006;35:837–55. doi: 10.1016/j.gtc.2006.09.008 . PubMed DOI

Colombel JF, Sandborn WJ, Rutgeerts P, Enns R, Hanauer SB, Panaccione R, et al.. Adalimumab for maintenance of clinical response and remission in patients with Crohn’s disease: the CHARM trial. Gastroenterology. 2007. Jan;132(1):52–65. doi: 10.1053/j.gastro.2006.11.041 Epub 2006 Nov 29. . PubMed DOI