Endoscopic remission can be predicted by golimumab concentrations in patients with ulcerative colitis treated with the changed label.
Journal
European journal of gastroenterology & hepatology
ISSN: 1473-5687
Titre abrégé: Eur J Gastroenterol Hepatol
Pays: England
ID NLM: 9000874
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
pubmed:
18
8
2020
medline:
7
8
2021
entrez:
18
8
2020
Statut:
ppublish
Résumé
In 2018, the European Medicines Agency (EMA) replaced a fixed 50 mg every 4-week maintenance regimen of golimumab for ulcerative colitis (UC) patients weighing <80 kg with new, flexible dosing that allows reactive dose optimization to 100 mg if clinically needed. We analyzed the endoscopic remission rates and pharmacokinetics of this new dosing regimen in real-life settings. We prospectively recruited 30 consecutive (17 with body weight <80 kg) patients with UC who received golimumab with the new EMA label. The primary endpoint was endoscopic remission (Mayo ≤1) assessed by centrally-read endoscopy at week 14 and year 1. Golimumab concentrations, measured at nine prespecified timepoints, were correlated with endoscopic remission and identified cut-offs. Endoscopic remission was achieved in 15/30 (50%) and 10/30 (33%) patients at week 14 and year 1, respectively. Reactive dose optimization to 100 mg maintenance was needed in 13/17 (76%) patients. Golimumab concentrations at week 6 predicted week 14 and year 1 endoscopic remission. Week 6 concentrations >10.7 µg/ml were a strong predictor for achievement and maintenance of endoscopic remission during the first year of treatment, while concentrations <5.1 µg/ml identified the opposite. One-third of the patients reached and maintained endoscopic remission during the first year of golimumab treatment, but the need for dose optimization to 100 mg every 4 weeks of maintenance was high in patients weighing <80 kg. Golimumab concentrations <5.1 µg/ml at week 6 identified patients who are unlikely to reach and maintain endoscopic remission with the new, flexible EMA label.
Sections du résumé
BACKGROUND
In 2018, the European Medicines Agency (EMA) replaced a fixed 50 mg every 4-week maintenance regimen of golimumab for ulcerative colitis (UC) patients weighing <80 kg with new, flexible dosing that allows reactive dose optimization to 100 mg if clinically needed. We analyzed the endoscopic remission rates and pharmacokinetics of this new dosing regimen in real-life settings.
METHODS
We prospectively recruited 30 consecutive (17 with body weight <80 kg) patients with UC who received golimumab with the new EMA label. The primary endpoint was endoscopic remission (Mayo ≤1) assessed by centrally-read endoscopy at week 14 and year 1. Golimumab concentrations, measured at nine prespecified timepoints, were correlated with endoscopic remission and identified cut-offs.
RESULTS
Endoscopic remission was achieved in 15/30 (50%) and 10/30 (33%) patients at week 14 and year 1, respectively. Reactive dose optimization to 100 mg maintenance was needed in 13/17 (76%) patients. Golimumab concentrations at week 6 predicted week 14 and year 1 endoscopic remission. Week 6 concentrations >10.7 µg/ml were a strong predictor for achievement and maintenance of endoscopic remission during the first year of treatment, while concentrations <5.1 µg/ml identified the opposite.
CONCLUSION
One-third of the patients reached and maintained endoscopic remission during the first year of golimumab treatment, but the need for dose optimization to 100 mg every 4 weeks of maintenance was high in patients weighing <80 kg. Golimumab concentrations <5.1 µg/ml at week 6 identified patients who are unlikely to reach and maintain endoscopic remission with the new, flexible EMA label.
Identifiants
pubmed: 32804854
doi: 10.1097/MEG.0000000000001843
pii: 00042737-202101000-00010
doi:
Substances chimiques
Antibodies, Monoclonal
0
golimumab
91X1KLU43E
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
54-61Références
Taxonera C, Iborra M, Bosca-Watts MM, Rubio S, Nantes Ó, Higuera R, et al. Early dose optimization of golimumab induces late response and long-term clinical benefit in moderately to severely active ulcerative colitis. Curr Med Res Opin. 2019; 35:1297–1304
Drobne D, Kurent T, Golob S, Švegl P, Rajar P, Hanžel J, et al. Optimised infliximab monotherapy is as effective as optimised combination therapy, but is associated with higher drug consumption in inflammatory bowel disease. Aliment Pharmacol Ther. 2019; 49:880–889
Drobne D, Kurent T, Golob S, Svegl P, Rajar P, Terzic S, et al. Success and safety of high infliximab trough levels in inflammatory bowel disease. Scand J Gastroenterol. 2018; 53:940–946
Roblin X, Rinaudo M, Del Tedesco E, Phelip JM, Genin C, Peyrin-Biroulet L, Paul S. Development of an algorithm incorporating pharmacokinetics of adalimumab in inflammatory bowel diseases. Am J Gastroenterol. 2014; 109:1250–1256
Janseen Biologics B.V. SIMPONI (Golimumab): Summary of Product Characteristics. 2019. Available at: https://www.ema.europa.eu/en/documents/product-information/simponi-epar-product-information_en.pdf . [Accessed 22 March 2020]
Magro F, Lopes S, Silva M, Coelho R, Portela F, Branquinho D, et al.; Portuguese IBD Group [GEDII]. Low golimumab trough levels at week 6 are associated with poor clinical, endoscopic and histological outcomes in ulcerative colitis patients: pharmacokinetic and pharmacodynamic sub-analysis of the Evolution Study. J Crohns Colitis. 2019; 13:1387–1393
Tursi A, Allegretta L, Buccianti N, Della Valle N, Elisei W, Forti G, et al. Effectiveness and safety of golimumab in treating outpatient ulcerative colitis: a real-life prospective, multicentre, observational study in Primary Inflammatory Bowel Diseases Centers. J Gastrointestin Liver Dis. 2017; 26:239–244
Berends SE, Strik AS, Jansen JM, de Boer NK, van Egmond PS, Brandse JF, et al. Pharmacokinetics of golimumab in moderate to severe ulcerative colitis: the GO-KINETIC study. Scand J Gastroenterol. 2019; 54:700706
Taxonera C, Rodríguez C, Bertoletti F, Menchén L, Arribas J, Sierra M, et al.; Collaborators. Clinical outcomes of golimumab as first, second or third anti-TNF agent in patients with moderate-to-severe ulcerative colitis. Inflamm Bowel Dis. 2017; 23:1394–1402
Orlandini B, Dragoni G, Variola A, Massella A, Bagnoli S, Campi R, Rogai F. Clinical efficacy and safety of golimumab in biologically experienced and naive patients with active ulcerative colitis: a real-life experience from two Italian IBD centers. J Dig Dis. 2018; 19:468–474
Bosca-Watts MM, Cortes X, Iborra M, Huguet JM, Sempere L, Garcia G, et al. Short-term effectiveness of golimumab for ulcerative colitis: observational multicenter study. World J Gastroenterol. 2016; 22:10432–10439
Bossuyt P, Baert F, D’Heygere F, Nakad A, Reenaers C, Fontaine F, et al.; Belgian IBD Research and Development Group. Early mucosal healing predicts favorable outcomes in patients with moderate to severe ulcerative colitis treated with golimumab: data from the real-life BE-SMART cohort. Inflamm Bowel Dis. 2019; 25:156–162
O’Connell J, Rowan C, Stack R, Harkin G, Parihar V, Chan G, et al. Golimumab effectiveness and safety in clinical practice for moderately active ulcerative colitis. Eur J Gastroenterol Hepatol. 2018; 30:1019–1026
Peyrin-Biroulet L, Sandborn W, Sands BE, Reinisch W, Bemelman W, Bryant RV, et al. Selecting therapeutic targets in inflammatory bowel disease (STRIDE): determining therapeutic goals for treat-to-target. Am J Gastroenterol. 2015; 110:1324–1338
Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. N Engl J Med. 1987; 317:1625–1629
Jairath V, Khanna R, Zou GY, Stitt L, Mosli M, Vandervoort MK, et al. Development of interim patient-reported outcome measures for the assessment of ulcerative colitis disease activity in clinical trials. Aliment Pharmacol Ther. 2015; 42:1200–1210
Vuitton L, Peyrin-Biroulet L, Colombel JF, Pariente B, Pineton de Chambrun G, Walsh AJ, et al. Defining endoscopic response and remission in ulcerative colitis clinical trials: an international consensus. Aliment Pharmacol Ther. 2017; 45:801–813
Detrez I, Dreesen E, Van Stappen T, de Vries A, Brouwers E, Van Assche G, et al. Variability in golimumab exposure: a “real-life” observational study in active ulcerative colitis. J Crohn’s Colitis. 2016; 10:575–581
Adedokun OJ, Xu Z, Marano CW, Strauss R, Zhang H, Johanns J, et al. Pharmacokinetics and exposure-response 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
Philip G, Cornillie F, Adedokun JO, Melsheimer R, Rutgeerts P, Colombel JF, Marano C. Early dose optimisation of golimumab in nonresponders to induction treatment for ulcerative colitis is effective and supported by pharmacokinetic data. J Crohns Colitis. 2019; 13:1257–1264
Berger AE, Duru G, de Vries A, Marini JC, Aoucheta D, Cornillie F, et al. Comparison of immunoassays for measuring serum levels of golimumab and antibodies against golimumab in ulcerative colitis: a retrospective observational study. Ther Drug Monit. 2019; 41:459–466
Strik AS, Berends SE, Mathôt RA, D’Haens GR, Löwenberg M. Golimumab for moderate to severe ulcerative colitis. Expert Rev Gastroenterol Hepatol. 2017; 11:401–406
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. J Gastroenterol. 2017; 52:1101–1111
Thorlund K, Druyts E, Eapen S, Mills E. Cost-effectiveness of golimumab versus infliximab and adalimumab for the treatment of moderate to severe ulcerative colitis. Value Heal. 2014; 17:A38
Ferrante M, Vermeire S, Fidder H, Schnitzler F, Noman M, Van Assche G, et al. Long-term outcome after infliximab for refractory ulcerative colitis. J Crohns Colitis. 2008; 2:219–225