- Fecal Incontinence
|Is the Pharmacokinetic Profile of a First Anti-TNF Predictive of the Clinical Outcome and Pharmacokinetics of a Second Anti-TNF?
Roblin X1, Vérot C1, Paul S2, Duru G3, Williet N1, Boschetti G4, Del Tedesco E1, Peyrin-Biroulet L5, Marc Phelip J1, Nancey S4, Flourie B4. Inflamm Bowel Dis. 2018 Apr 26. doi: 10.1093/ibd/izy111. [Epub ahead of print]
1 Department of Gastroenterology, University Hospital of Saint-Etienne, Saint-Etienne, France.
2 Department of Immunology, University Hospital of Saint-Etienne, Saint-Etienne, France.
3 Department of Statistics, University Claude Bernard Lyon 1, Lyon, France.
4 Department of Gastroenterology, Hospices Civils de Lyon, University Claude Bernard Lyon and INSERM, Lyon, France.
5 Department of Gastroenterology, University Hospital of Nancy, Nancy, France.
AIM: The aim of this study was to evaluate prospectively the clinical outcomes and pharmacokinetics of a second anti-TNF according to the pharmacokinetics of the first anti-TNF in patients with inflammatory boweldisease (IBD).
METHODS: In patients in loss of response (LOR) to a first optimized anti-TNF and switched to a second anti-TNF, pharmacokinetics of anti-TNF were measured at the switch time, 30 weeks later, at the time of LOR, or at the end of the study (102 weeks).
RESULTS: At the switch time, patients (n = 59) belonged to 4 groups according to the pharmacokinetics of the first anti-TNF: group 1 (n = 18), therapeutic trough levels; group 2 (n = 13) undetectable trough levels with antibodies against anti-TNF; group 3 (n = 13) without antibodies against anti-TNF; and group 4 (n = 15) subtherapeutic trough levels. After switching, the failure rates at week 30 and during the follow-up were as follows, respectively: in group 1 with therapeutic levels, 50% and 78%, despite therapeutic levels of the second anti-TNF in 83% of cases; in group 2 with undetectable levels and antibodies, 15% and 69% with undetectable levels of the second anti-TNF and antibodies in 85% of cases; in group 3 with undetectable levels without antibodies, 0% and 31% with therapeutic levels in 77% of cases; in group 4 with subtherapeutic levels, 13% and 33% with therapeutic levels in 73% of cases. Clinical remission rates were significantly lower (P ≤ 0.05) in groups 1 and 2 with therapeutic or undetectable levels with antibodies than in the 2 other groups.
CONCLUSION: In the case of LOR with therapeutic levels of the first anti-TNF or undetectable levels with antibodies, the switch to a second anti-TNF results in pharmacokinetic profile similar to the first one and again in LOR in most of the patients.