Endoscopic remission can be predicted by golimumab concentrations in patients with ulcerative colitis treated with the changed label

Abstract

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.

Effectiveness of golimumab in patients with ulcerative colitis: results of a real-life study in Switzerland

“…14 Real-world data remain important to assess performance of a drug under non-ideal conditions in clinical practice, when treatment cannot be limited to patients fulfilling narrow inclusion criteria, 15 with only about one in four real-life UC patients qualifying for participation in randomized controlled trials. 16 Some real-world data and post-marketing studies for golimumab in UC are available, 14,[17][18][19][20][21][22][23][24][25][26] these generally confirmed effectiveness and safety of golimumab treatment. In some of these studies, clinical response and remission, 18,22,23,25 and persistence rates, 17 were higher in anti-TNF naïve patients compared with non-naïve patients.…”

Systematic Literature Review of Real-World Evidence on Dose Escalation and Treatment Switching in Ulcerative Colitis

“… 35 Dose escalation by interval shortening alone was reported in 31 studies ( Supplementary Table 6 ); 21–23 , 26–28 , 31 , 32 , 34 , 36–38 , 41 , 44 , 46 , 47 , 49–52 , 55 , 58 , 59 , 64–68 , 70 , 71 , 74 , 75 this most commonly occurred with IFX (from 5 mg/kg every 8 to 4 weeks) and ADA (from 40 mg every 2 weeks to once weekly).

Figure 2 Proportion of patients treated with dose escalation due to loss of response 31 , 44 , 46 , 63 , 66–68 , 75 , 76 or any reason. 22–29 , 32 , 34 , 35 , 37 , 38 , 40–42 , 45 , 47–52 , 55 , 57–62 , 64 , 65 , 69 , 71 , 72 , 74 Studies originating in multiple countries and including multiple anti-TNF therapies were counted more than once, giving a total number of references higher than the 48 publications found.

…”

Editorial: golimumab thresholds to achieve stringent medium‐ and long‐term therapeutic outcomes in patients with ulcerative colitis

“…1,2 However, there are only limited data regarding golimumab and the ideal drug concentration threshold to target when applying TDM in clinical practice. [3][4][5][6][7] Taxonera et al performed a multicenter, cross-sectional, cohort study in 52 patients with ulcerative colitis (UC) treated with golimumab and found positive associations between maintenance golimumab trough concentrations (GTCs) with several stringent sole and composite outcomes, such as clinical remission (Partial Mayo Score…”

“…These results are in line with previous studies showing that higher golimumab concentrations are associated with higher rates of favourable therapeutic outcomes. [3][4][5][6][7] A post hoc analysis of the phase 2/3 PURSUIT randomised controlled trials (RCTs) identified golimumab concentrations thresholds of 0.9 μg/ml at week 28 and 1.4 μg/ml at week 44 with clinical remission at week 54. 4 This study has several inherent limitations.…”

“…Therapeutic drug monitoring (TDM) has emerged as a useful monitoring tool for optimising anti‐TNF therapy, especially infliximab and adalimumab 1,2 . However, there are only limited data regarding golimumab and the ideal drug concentration threshold to target when applying TDM in clinical practice 3–7 …”