Background: Vedolizumab and TNF antagonists are biologicals with different modes of action. Vedolizumab a humanized monoclonal antibody that specifically binds to the α4β7 integrin, blocks the interaction of the α4β7 integrin with MAdCAM-1 and inhibits the migration of memory T-lymphocytes across the endothelium into inflamed gastrointestinal parenchymal tissue. TNF antagonists neutralize the proinflammatory cytokine TNF, but the mode of action still remains unclear. Induction of mucosal T-cell apoptosis and down-regulation of proinflammatory cytokines are only some of the identified mechanisms. 50% of IBD patients have a chronic active course of disease. Some of them suffer from a severe, so far therapy refractory disease course. A combination therapy of different biologicals might be effective in these patients.
Methods: 7 patients with IBD (4 with Crohn's disease and 3 with ulcerative colitis) were treated with vedolizumab in combination with a TNF antagonist as an individual healing attempt through a case by case decision. Patients were seen as standard clinical care at baseline, week 2, 6, 14 and week 30. CDAI, CRP and calprotectin were assessed at all visits. Sonography and ileocolonoscopy or sigmoidoscopy (in ulcerative colitis patients) was performed at baseline, week 14 and week 30. SES-CDEIS and complete Mayo score was assed also at baseline, week 14 and week 30.
Results: Mean CDAI at baseline: 410 (CD), Mayo score 11 (UC), CRP 39.76 mg/l (both UC and CD), fecal calprotectin 2100 mg/kg (UC), 883 (CD), SES-CDEIS 31 (CD). CRP at week 2: and 6: 35.74 mg/l and 21.21 mg/l (both UC and CD), calprotectin at week 2 and 6: 1956 mg/kg (UC), 798 (CD), 1287 mg/kg (UC), 580 (CD). Mean CDAI at week 2 and 6: 404 and 383 (CD). Mean CDAI at week 14: 262 (CD), Mayo score 8 (UC), CRP 15.71 mg/l (both UC and CD), fecal calprotectin 760 mg/kg (UC), 465 (CD), SES-CDEIS 22 (CD). Mean CDAI at week 30: 172 (CD), Mayo score 4 (UC), CRP 3.46 mg/l (both UC and CD), fecal calprotectin 377 mg/kg (UC), 215 (CD), SES-CDEIS 11 (CD). Even so none of the patients were in complete deep remission, a significantly improvement could be seen in disease symptoms like abdominal pain and stool frequency and a significant improvement in the mucosal inflammation could be assessed by endoscopy.
Conclusions: Combination therapy was well tolerated and effective. No severe infections or other severe adverse events could be seen so far. Further and larger clinical trials have to be performed in the future to investigate the efficacy and safety of anti-integrin antibodies and TNF antagonists as a combination therapy for a fast remission induction or as a maintenance combination therapy.