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Long-Term Efficacy and Safety of Golimumab for Ulcerative Colitis in a Pediatric Inflammatory Bowel Disease Center in Japan

  • Tokita, Kazuhide (Center for Pediatric Inflammatory Bowel Disease, Division of Gastroenterology, National Center for Child Health and Development) ;
  • Shimizu, Hirotaka (Center for Pediatric Inflammatory Bowel Disease, Division of Gastroenterology, National Center for Child Health and Development) ;
  • Takeuchi, Ichiro (Center for Pediatric Inflammatory Bowel Disease, Division of Gastroenterology, National Center for Child Health and Development) ;
  • Shimizu, Toshiaki (Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine) ;
  • Arai, Katsuhiro (Center for Pediatric Inflammatory Bowel Disease, Division of Gastroenterology, National Center for Child Health and Development)
  • Received : 2022.02.14
  • Accepted : 2022.08.09
  • Published : 2022.11.15

Abstract

Purpose: Golimumab (GLM) is an anti-tumor necrosis factor (TNF)-α antibody preparation known to be less immunogenic than infliximab (IFX) or adalimumab. Few reports on GLM in pediatric patients with ulcerative colitis (UC) are available. This study aimed to review the long-term durability and safety of GLM in a pediatric center. Methods: The medical records of 17 pediatric patients (eight boys and nine girls) who received GLM at the National Center for Child Health and Development were retrospectively reviewed. Results: The median age at GLM initiation was 13.9 (interquartile range 12.0-16.3) years. Fourteen patients had pancolitis, and 11 had severe disease (pediatric ulcerative colitis activity index ≥65). Ten patients were biologic-naive, and 50% achieved corticosteroid-free remission at week 54. Two patients discontinued prior anti-TNF-α agents because of adverse events during remission. Both showed responses to GLM without unfavorable events through week 54. However, the efficacy of GLM in patients who showed primary nonresponse or loss of response to IFX was limited. Four of the five patients showed non-response at week 54. Patients with severe disease had significantly lower corticosteroid-free remission rate at week 54 than those without severe disease. No severe adverse events were observed during the study period. Conclusion: GLM appears to be safe and useful for pediatric patients with UC. Patients with mild to moderate disease who responded to but had some adverse events with prior biologics may be good candidates for GLM. Its safety and low immunogenicity profile serve as favorable options for selected children with UC.

Keywords

Acknowledgement

This work was supported by a Grant-in-Aid for the National Center for Child Health and Development (2019A-3) and Research Grants for Research on Intractable Disease (20FC1042) from the Ministry of Health, Labour and Welfare, Japan.

References

  1. Benchimol EI, Fortinsky KJ, Gozdyra P, Van den Heuvel M, Van Limbergen J, Griffiths AM. Epidemiology of pediatric inflammatory bowel disease: a systematic review of international trends. Inflamm Bowel Dis 2011;17:423-39. https://doi.org/10.1002/ibd.21349
  2. Bequet E, Sarter H, Fumery M, Vasseur F, Armengol-Debeir L, Pariente B, et al. Incidence and phenotype at diagnosis of very-early-onset compared with later-onset paediatric inflammatory bowel disease: a population-based study [1988-2011]. J Crohns Colitis 2017;11:519-26.
  3. Ishige T, Tomomasa T, Hatori R, Tatsuki M, Igarashi Y, Sekine K, et al. Temporal trend of pediatric inflammatory bowel disease: analysis of national registry data 2004 to 2013 in Japan. J Pediatr Gastroenterol Nutr 2017;65:e80-2. https://doi.org/10.1097/MPG.0000000000001547
  4. Ungaro R, Mehandru S, Allen PB, Peyrin-Biroulet L, Colombel JF. Ulcerative colitis. Lancet 2017;389:1756-70. https://doi.org/10.1016/S0140-6736(16)32126-2
  5. D'Haens GR, Panaccione R, Higgins PD, Vermeire S, Gassull M, Chowers Y, et al. The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn's and Colitis Organization: when to start, when to stop, which drug to choose, and how to predict response?. Am J Gastroenterol 2011;106:199-212; quiz 213. Erratum in: Am J Gastroenterol 2011;106:375.
  6. Hyams J, Damaraju L, Blank M, Johanns J, Guzzo C, Winter HS, et al. Induction and maintenance therapy with infliximab for children with moderate to severe ulcerative colitis. Clin Gastroenterol Hepatol 2012;10:391-9.e1. https://doi.org/10.1016/j.cgh.2011.11.026
  7. Hyams JS, Lerer T, Griffiths A, Pfefferkorn M, Stephens M, Evans J, et al. Outcome following infliximab therapy in children with ulcerative colitis. Am J Gastroenterol 2010;105:1430-6. https://doi.org/10.1038/ajg.2009.759
  8. Aloi M, Bramuzzo M, Arrigo S, Romano C, D'Arcangelo G, Lacorte D, et al. Efficacy and safety of adalimumab in pediatric ulcerative colitis: a real-life experience from the SIGENP-IBD registry. J Pediatr Gastroenterol Nutr 2018;66:920-5. https://doi.org/10.1097/MPG.0000000000001883
  9. Takeuchi I, Kaburaki Y, Arai K, Shimizu H, Hirano Y, Nagata S, et al. Infliximab for very early-onset inflammatory bowel disease: a tertiary center experience in Japan. J Gastroenterol Hepatol 2020;35:593-600. https://doi.org/10.1111/jgh.14836
  10. Freling E, Baumann C, Cuny JF, Bigard MA, Schmutz JL, Barbaud A, et al. Cumulative incidence of, risk factors for, and outcome of dermatological complications of anti-TNF therapy in inflammatory bowel disease: a 14-year experience. Am J Gastroenterol 2015;110:1186-96. https://doi.org/10.1038/ajg.2015.205
  11. Shealy DJ, Cai A, Staquet K, Baker A, Lacy ER, Johns L, et al. Characterization of golimumab, a human monoclonal antibody specific for human tumor necrosis factor α. MAbs 2010;2:428-39. https://doi.org/10.4161/mabs.12304
  12. Sandborn WJ, Feagan BG, Marano C, Zhang H, Strauss R, Johanns J, et al. Subcutaneous golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology 2014;146:85-95; quiz e14-5. https://doi.org/10.1053/j.gastro.2013.05.048
  13. Sandborn WJ, Feagan BG, Marano C, Zhang H, Strauss R, Johanns J, et al. Subcutaneous golimumab maintains clinical response in patients with moderate-to-severe ulcerative colitis. Gastroenterology 2014;146:96-109.e1. https://doi.org/10.1053/j.gastro.2013.06.010
  14. Hibi T, Imai Y, Senoo A, Ohta K, Ukyo Y. Efficacy and safety of golimumab 52-week maintenance therapy in Japanese patients with moderate to severely active ulcerative colitis: a phase 3, double-blind, randomized, placebo-controlled study-(PURSUIT-J study). J Gastroenterol 2017;52:1101-11. https://doi.org/10.1007/s00535-017-1326-1
  15. Hyams JS, Chan D, Adedokun OJ, Padgett L, Turner D, Griffiths A, et al. Subcutaneous golimumab in pediatric ulcerative colitis: pharmacokinetics and clinical benefit. Inflamm Bowel Dis 2017;23:2227-37. https://doi.org/10.1097/MIB.0000000000001262
  16. Xu Y, Adedokun OJ, Chan D, Hu C, Xu Z, Strauss RS, et al. Population pharmacokinetics and exposureresponse modeling analyses of golimumab in children with moderately to severely active ulcerative colitis. J Clin Pharmacol 2019;59:590-604.
  17. Turner D, Ruemmele FM, Orlanski-Meyer E, Griffiths AM, de Carpi JM, Bronsky J, et al. Management of paediatric ulcerative colitis, part 2: acute severe colitis-an evidence-based consensus guideline from the European Crohn's and Colitis Organization and the European Society of Paediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr 2018;67:292-310. https://doi.org/10.1097/MPG.0000000000002036
  18. Turner D, Otley AR, Mack D, Hyams J, de Bruijne J, Uusoue K, et al. Development, validation, and evaluation of a pediatric ulcerative colitis activity index: a prospective multicenter study. Gastroenterology 2007;133:423-32. https://doi.org/10.1053/j.gastro.2007.05.029
  19. Levine A, Griffiths A, Markowitz J, Wilson DC, Turner D, Russell RK, et al. Pediatric modification of the Montreal classification for inflammatory bowel disease: the Paris classification. Inflamm Bowel Dis 2011;17:1314-21. https://doi.org/10.1002/ibd.21493
  20. Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med 1987;317:1625-9. https://doi.org/10.1056/NEJM198712243172603
  21. Lobaton T, Bessissow T, De Hertogh G, Lemmens B, Maedler C, Van Assche G, et al. The Modified Mayo Endoscopic Score (MMES): a new index for the assessment of extension and severity of endoscopic activity in ulcerative colitis patients. J Crohns Colitis 2015;9:846-52. https://doi.org/10.1093/ecco-jcc/jjv111
  22. Ordas I, Eckmann L, Talamini M, Baumgart DC, Sandborn WJ. Ulcerative colitis. Lancet 2012;380:1606-19. https://doi.org/10.1016/S0140-6736(12)60150-0
  23. Taxonera C, Rodriguez C, Bertoletti F, Menchen L, Arribas J, Sierra M, et al. Clinical outcomes of golimumab as first, second or third anti-TNF agent in patients with moderate-to-severe ulcerative colitis. Inflamm Bowel Dis 2017;23:1394-402. https://doi.org/10.1097/MIB.0000000000001144
  24. Pugliese D, Privitera G, Rogai F, Variola A, Viola A, Laterza L, et al. Two-year effectiveness and safety of golimumab in ulcerative colitis: an IG-IBD study. United European Gastroenterol J 2021;9:102-9. https://doi.org/10.1177/2050640620974308
  25. Raine T, Bonovas S, Burisch J, Kucharzik T, Adamina M, Annese V, et al. ECCO guidelines on therapeutics in ulcerative colitis: medical treatment. J Crohns Colitis 2022;16:2-17. https://doi.org/10.1093/ecco-jcc/jjab178
  26. Singh S, Proudfoot JA, Dulai PS, Xu R, Feagan BG, Sandborn WJ, et al. Comparative efficacy and speed of onset of action of infliximab vs golimumab in ulcerative colitis. Clin Gastroenterol Hepatol 2020;18:424-31.e7. https://doi.org/10.1016/j.cgh.2019.05.019
  27. Adedokun OJ, Xu Z, Marano CW, Strauss R, Zhang H, Johanns J, et al. Pharmacokinetics and exposureresponse relationship of golimumab in patients with moderately-to-severely active ulcerative colitis: results from phase 2/3 PURSUIT induction and maintenance studies. J Crohns Colitis 2017;11:35-46. https://doi.org/10.1093/ecco-jcc/jjw133
  28. Turner D, Ruemmele FM, Orlanski-Meyer E, Griffiths AM, de Carpi JM, Bronsky J, et al. Management of paediatric ulcerative colitis, part 1: ambulatory care-an evidence-based guideline from European Crohns and Colitis Organization and European Society of Paediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr 2018;67:257-91. Erratum in: J Pediatr Gastroenterol Nutr 2020;71:794. https://doi.org/10.1097/MPG.0000000000002967
  29. Stordal K, Jahnsen J, Bentsen BS, Moum B. Pediatric inflammatory bowel disease in southeastern Norway: a five-year follow-up study. Digestion 2004;70:226-30. https://doi.org/10.1159/000082893
  30. Ito N, Takeuchi I, Kyodo R, Hirano Y, Sato T, Usami M, et al. Features and outcomes of children with ulcerative colitis who undergo a diagnostic change: a single-center experience. Pediatr Gastroenterol Hepatol Nutr 2021;24:357-65. https://doi.org/10.5223/pghn.2021.24.4.357
  31. Soto Lopes MS, Trope BM, Rochedo Rodriguez MP, Grynszpan RL, Cuzzi T, Ramos-E-Silva M. Paradoxical reaction to golimumab: tumor necrosis factor α inhibitor inducing psoriasis pustulosa. Case Rep Dermatol 2013;5:326-31. https://doi.org/10.1159/000350930
  32. Mateo S, Garcia-Martinez FJ, Sanchez-Aguilar D, Amarelo J, Toribio J. Psoriasiform exfoliative erythroderma induced by golimumab. Clin Exp Dermatol 2014;39:813-5. https://doi.org/10.1111/ced.12402