Search
Close
Search
Advanced Search
Search Menu
AI Discovery Assistant

Abstract

Background

Inflammation and thrombosis are intertwined. Therefore, ulcerative colitis (UC) and Crohn’s disease (CD) patients tend to have an altered clot-lysis (CL) profile, which may reflect their higher risk for venous thromboembolic events (VTE). Blocking TNF by infliximab (IFX) has been shown to normalise the CL profile of IBD patients responding to the therapy.1 We aimed to investigate whether the gut-specific, anti-integrin vedolizumab (VDZ) exhibits a similar effect on the CL profile of IBD patients upon treatment response.

Methods

Forty-two IBD patients initiating IFX (n = 20) or VDZ (n = 22) therapy for active UC (median total Mayo score 8) or CD (median Harvey-Bradshaw Index (HBI) 9), and 22 healthy controls (HC) were prospectively included. None of the patients had a history of VTE. Plasma was collected before the first infusion (Week 0, Week 0) and after induction therapy (Week 14). From the CL profile, area under the curve (AUC; global marker for coagulation/fibrinolysis), 50% clot-lysis time (CLT; marker for fibrinolytic capacity), amplitude (marker for clot formation) and time to peak (tmax; marker for clot formation rate) were deduced.1 Disease remission (Week 14) was defined by partial Mayo score ≤2 and Mayo endoscopic sub-score ≤1 (UC) or HBI ≤5 and C-reactive protein concentration (CRP) ≤5 mg/l (when baseline CRP was elevated) (CD). Results were expressed relative to the values of the plasma pool of HC ( = 100%).

Results

Prior to biological treatment, AUC and amplitude were significantly higher in IBD patients as compared with HC (161 [111–211] % vs. 101 [79–133) %; p = 0.001 and 127 [104–148] % vs. 94 [85–114] %; p = 0.001, respectively). Upon induction therapy, response to either IFX or VDZ therapy was accompanied by a significant decrease in AUC (p = 0.014, p = 0.010) and amplitude (p = 0.027, p = 0.020) to values observed as those in HC (Table 1). Baseline AUC and amplitude were already lower in Week 14 VDZ responders compared with non-responders (p = 0.096 and p = 0.048). From Week 0 to Week 14, tmax was significantly prolonged in IFX responders (p = 0.004), whereas the opposite was observed for VDZ responders (p = 0.044) (Table 1). No patient developed a VTE during 1-year study follow-up.

Table 1.
Open in new tab

The haemostatic parameters of HC and IBD patients before and after IFX or VDZ induction therapy. Values are expressed as median [IQR] and relative to the values of the plasma pool of HC (=100%). RESP, responder; NA, not applicable.

Earlier anti-TNF (n, %)Week 0Week 0Week 0Week 0Week 14Week 14Week 14Week 14
Tmax (min)50% CLT (%)AUC (%)Amplitude (%)Tmax (min)50% CLT (%)AUC (%)Amplitude (%)
HC (n = 22)NA44 [26––57]103 [95––112]101 [79––133]94 [85–114]NANANANA
IBD –VDZ RESP. (n = 10)5034 [16–61]103 [81–143]125 [96–180]116 [103–139]31 [18–47]101 [78–136]104 [78–145]101 [89–120]
VDZ NON-RESP. (n = 12)8330 [18–39]122 [108–154]184 [132–273]140 [124–166]24 [16–44]135 [110–148]203 [176–256]137 [128–178]
IBD –IFX RESP. (n = 10)3026 [21–39]123 [98–136]167 [78–212]126 [98–166]36 [27–45]96 [81–100]85 [68–100]89 [65–99]
IFX NON-RESP. (n = 10)4030 [20–42]115 [93–138]128 [106–167]110 [93–128]32 [24–39]108 [96–118]123 [87–147]102 [91–130]
Earlier anti-TNF (n, %)Week 0Week 0Week 0Week 0Week 14Week 14Week 14Week 14
Tmax (min)50% CLT (%)AUC (%)Amplitude (%)Tmax (min)50% CLT (%)AUC (%)Amplitude (%)
HC (n = 22)NA44 [26––57]103 [95––112]101 [79––133]94 [85–114]NANANANA
IBD –VDZ RESP. (n = 10)5034 [16–61]103 [81–143]125 [96–180]116 [103–139]31 [18–47]101 [78–136]104 [78–145]101 [89–120]
VDZ NON-RESP. (n = 12)8330 [18–39]122 [108–154]184 [132–273]140 [124–166]24 [16–44]135 [110–148]203 [176–256]137 [128–178]
IBD –IFX RESP. (n = 10)3026 [21–39]123 [98–136]167 [78–212]126 [98–166]36 [27–45]96 [81–100]85 [68–100]89 [65–99]
IFX NON-RESP. (n = 10)4030 [20–42]115 [93–138]128 [106–167]110 [93–128]32 [24–39]108 [96–118]123 [87–147]102 [91–130]
Table 1.
Open in new tab

The haemostatic parameters of HC and IBD patients before and after IFX or VDZ induction therapy. Values are expressed as median [IQR] and relative to the values of the plasma pool of HC (=100%). RESP, responder; NA, not applicable.

Earlier anti-TNF (n, %)Week 0Week 0Week 0Week 0Week 14Week 14Week 14Week 14
Tmax (min)50% CLT (%)AUC (%)Amplitude (%)Tmax (min)50% CLT (%)AUC (%)Amplitude (%)
HC (n = 22)NA44 [26––57]103 [95––112]101 [79––133]94 [85–114]NANANANA
IBD –VDZ RESP. (n = 10)5034 [16–61]103 [81–143]125 [96–180]116 [103–139]31 [18–47]101 [78–136]104 [78–145]101 [89–120]
VDZ NON-RESP. (n = 12)8330 [18–39]122 [108–154]184 [132–273]140 [124–166]24 [16–44]135 [110–148]203 [176–256]137 [128–178]
IBD –IFX RESP. (n = 10)3026 [21–39]123 [98–136]167 [78–212]126 [98–166]36 [27–45]96 [81–100]85 [68–100]89 [65–99]
IFX NON-RESP. (n = 10)4030 [20–42]115 [93–138]128 [106–167]110 [93–128]32 [24–39]108 [96–118]123 [87–147]102 [91–130]
Earlier anti-TNF (n, %)Week 0Week 0Week 0Week 0Week 14Week 14Week 14Week 14
Tmax (min)50% CLT (%)AUC (%)Amplitude (%)Tmax (min)50% CLT (%)AUC (%)Amplitude (%)
HC (n = 22)NA44 [26––57]103 [95––112]101 [79––133]94 [85–114]NANANANA
IBD –VDZ RESP. (n = 10)5034 [16–61]103 [81–143]125 [96–180]116 [103–139]31 [18–47]101 [78–136]104 [78–145]101 [89–120]
VDZ NON-RESP. (n = 12)8330 [18–39]122 [108–154]184 [132–273]140 [124–166]24 [16–44]135 [110–148]203 [176–256]137 [128–178]
IBD –IFX RESP. (n = 10)3026 [21–39]123 [98–136]167 [78–212]126 [98–166]36 [27–45]96 [81–100]85 [68–100]89 [65–99]
IFX NON-RESP. (n = 10)4030 [20–42]115 [93–138]128 [106–167]110 [93–128]32 [24–39]108 [96–118]123 [87–147]102 [91–130]
Conclusions

Response to both IFX and VDZ induction therapy is reflected in a diminution of the CL profile of the IBD patient. Upon response, time to clot formation was prolonged by IFX but shortened by VDZ responders. Inhibition of the α4β7 integrin: fibronectin interaction by VDZ might play a role and deserves further investigation.

Reference

1. Bollen et al. Short-term effect of infliximab is reflected in the clot lysis profile of patients with inflammatory bowel disease: a prospective study. Inflamm Bowel Dis, 2015;21: 570–8.

Topic:
Issue Section:
03. Poster presentations > c. Clinical: Therapy and observation
This content is only available as a PDF.
Copyright © 2018 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com
You do not currently have access to this article.
Download all slides