Introduction
Prior evidence suggests a positive exposure-response relationship between vedolizumab (VDZ) serum concentrations and treatment outcomes in ulcerative colitis (UC). The exposure-response relationship for more stringent histological and endoscopic outcomes, however, has not yet been characterised.
Aims & Methods
LOVE-UC was a multicentre international (Belgium, the Netherlands, and Hungary) open label prospective study in patients with moderately to severely active UC treated with standard doses of VDZ for 1 year. VDZ serum concentrations were measured at trough prior to every infusion. Endoscopy was performed at baseline, week 26, and week 52. Biopsies from the most severely affected area and endoscopic videos were scored by blinded central readers. Symptomatic remission was defined as a rectal bleeding score of 0 and stool frequency score of ≤1. Clinical remission was defined as a total Mayo score of ≤2 with no sub-score >1. Endoscopic improvement and remission were defined as a Mayo endoscopic score of ≤1 and 0, respectively. Histological remission was defined as a Robarts Histopathology Index <3 without neutrophils. Non-responder imputation was used if endoscopic or histological assessment was unavailable.
Results
A total of 121 patients (61 male, 62 with prior exposure to tumour necrosis factor antagonists, mean total Mayo score at baseline of 9) received at least one infusion of VDZ. At week 26, 57.0% (69/121) of patients were in symptomatic remission, 45.5% (55/121) in clinical remission, 50.4% (61/121) had endoscopic improvement, and 24.8% (30/121) had endoscopic remission. 35.5% (43/121) of patients had combined histological remission and endoscopic improvement, 19.8% (24/121) of patients had combined histological and endoscopic remission. Patients with higher VDZ serum concentrations at week 6 were more likely to meet these endpoints at week 26 (Table 1). More stringent outcomes were associated with higher concentration thresholds at week 6 (area under the receiver operating characteristic curve): 23.5 mg/L (0.608; P = 0.054) for symptomatic remission, 28.5 mg/L (0.607, P = 0.052) for clinical remission, 30.2 mg/L (0.647; P = 0.008) for endoscopic improvement, 31.5 mg/L (0.621; P = 0.054) for endoscopic remission, 30.2 mg/l (0.678; P = 0.002) for combined histological remission and endoscopic improvement, and 30.2 mg/L (0.673; P= 0.011) for combined histological and endoscopic remission.
Table 1. Median vedolizumab serum concentrations at week 6 based on treatment outcomes at week 26 in ulcerative colitis.
Treatment outcome at week 26
| Median (interquartile range) vedolizumab serum concentration in mg/L at week 6 | P-value
|
|---|
| Outcome achieved
| Outcome not achieved
|
|
Symptomatic remission
| 33.3 (26.3–38.0)
| 28.0 (21.8–38.9)
| 0.060
|
Clinical remission
| 34.0 (27.0–38.6)
| 28.0 (22.8–38.7)
| 0.061
|
Endoscopic improvement
| 34.0 (27.6–41.0)
| 28.0 (22.0–38.1)
| 0.009
|
Endoscopic remission
| 35.0 (27.0–41.0)
| 30.0 (23.0–38.0)
| 0.048
|
Histological remission
| 34.0 (27.0–41.0)
| 28.0 (22.5–37.5)
| 0.006
|
Combined histological remission and endoscopic improvement
| 36.0 (30.2–41.0)
| 28.0 (22.0–37.3)
| 0.001
|
Combined histological and endoscopic remission
| 37.0 (30.4–41.0)
| 30.0 (23.0–37.0)
| 0.010
|
Conclusion
VDZ serum concentrations were positively associated with clinical, endoscopic, and histological treatment outcomes in UC. More stringent outcomes were associated with higher concentration thresholds. The discriminative ability of serum concentrations to differentiate responders from non-responders was limited as indicated by the receiver operating characteristic curves.
Disclosure
JH received speaker’s fees from Abbvie, Janssen, and Takeda; consulting fees from Alimentiv Inc. FB reports grants/research supports from AbbVie, Amgen, Takeda, Janssen, honoraria or consultation fees from AbbVie, Amgen, Arena, MSD, Celgene, Kabi-Fresenius, Takeda, Ferring, Pfizer, Norgine, Janssen and participation in a company sponsored speaker's bureau for AbbVie, MSD, Takeda, Ferring, Pfizer, Janssen. ML served as speaker and/or principal investigator for Abbvie, Celgene, Covidien, Dr. Falk, Ferring Pharmaceuticals, Gilead, GlaxoSmithKline, Janssen-Cilag, Merck Sharp & Dohme, Pfizer, Protagonist therapeutics, Receptos, Takeda, Tillotts, Tramedico and has received research grants from AbbVie, Merck Sharp & Dohme, Achmea healthcare and ZonMW. MF reports research support from AbbVie, Amgen, Biogen, Janssen, Pfizer, Takeda and Viatris; speaker’s fees from AbbVie, Amgen, Biogen, Boehringer Ingelheim, Falk, Ferring, Janssen-Cilag, Lamepro, MSD, Mylan, Pfizer, Sandoz, Takeda and Truvion Healthcare consultancy fees from AbbVie, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Janssen-Cilag, Medtronic, MSD, Pfizer, Regeneron, Samsung Bioepis, Sandoz, Takeda and Thermo Fisher. PB reports research grants from Abbvie, Amgen, Celltrion, Mylan, Pfizer and Takeda; Lecture fees from AbbVie, Celltrion, Janssen, Lilly and Takeda; Lecture fee; and consulting fees Abbvie, Arena pharmaceuticals, BMS, Celltrion, Dr Falk, Galapagos, Janssen, Lilly, Pentax, PSI-CRO, Roche, Takeda and Tetrameros. FH has served on advisory boards or as speaker for Abbvie, Janssen-Cilag, MSD, Takeda, Pfizer, Celltrion, Teva, Sandoz and Dr Falk, and has received funding (Grants/Honoraria) from Janssen-Cilag, Abbvie and Takeda. DF has received educational grants from AbbVie, Takeda, MSD, and Janssen; and has received honoraria fees for lectures or consultancy from Ferring, Falk, Chiesi, AbbVie, MSD, Centocor, Pfizer, Amgen, Janssen, Mundipharma, Takeda, and Hospira. HP scientific grants, advisory board, lecture or travel fees from Abbvie, Janssen, Takeda, Pfizer, Ferring, MSD, Fresenius Kabi, Johnson & Johnson, Sandoz. SV received grants from AbbVie, J&J, Pfizer, Takeda and Galapagos; consulting and/or speaking fees from: AbbVie, Abivax, AbolerIS Pharma, AgomAb, Alimentiv, Arena Pharmaceuticals, AstraZeneca, Avaxia, BMS, Boehringer Ingelheim, Celgene, CVasThera, Cytoki Pharma, Dr Falk Pharma, Ferring, Galapagos, Genentech-Roche, Gilead, GSK, Hospira, Imidomics, Janssen, J&J, Lilly, Materia Prima, MiroBio, Morphic, MrMHealth, Mundipharma, MSD, Pfizer, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance, Tillots Pharma AG, Zealand Pharma. GD received consultancy fees from AbbVie, Alimentiv, Bristol Meiers Squibb, Boehringer Ingelheim, Celltrion, Eli Lilly, Galapagos, GlaxoSmithKline, Gossamer Bio, Pfizer, Immunic, Johnson and Johnson, Takeda, Prometheus Biosciences, Prometheus Laboratories, Protagonist, Samsung, Seres, Tillotts, Ventyx. All other authors report no conflicts of interest.
