Anneline Cremer

Infliximab Trough Levels at Induction to Predict Treatment Failure During Maintenance

Background: Infliximab (IFX) is indicated for the treatment of inflammatory bowel diseases (IBD). Nevertheless, loss of response (LOR) to IFX is reported in up to 10% to 30% of patients within the first year of treatment. Our objective was to evaluate the impact of the pharmacokinetics of IFX at induction on treatment failure. Methods: This is a longitudinal cohort study on 269 patients with IBD treated with IFX in a single center. A total of 2331 blood samples were prospectively collected from 2007 until March 2015 with a retrospective analysis of clinical data. IFX trough levels (TLs) were measured by enzyme-linked immunosorbent assay. Antibodies to IFX were measured by drug-sensitive bridging assay. Results: During follow-up, patients were defined according to treatment outcome. At week 6, median IFX TL in patients requiring a switch to another treatment due to LOR (LOR switched group) (2.32 &mgr;g/mL [0.12–19.93 &mgr;g/mL]) was lower than in patients with long-term response (long-term responders) (8.66 &mgr;g/mL [0.12–12.09 &mgr;g/mL], P = 0.007) and in patients responding to optimization (LOR optimized group) (7.28 &mgr;g/mL [0.17–14.91 &mgr;g/mL], P = 0.021). At week 2, median IFX TL was lower in the LOR switched group (5.7 &mgr;g/mL [0.15–12.09 &mgr;g/mL]) compared with the long-term responders (11.92 &mgr;g/mL [0.14–19.93 &mgr;g/mL], P = 0.041) but no significant difference was reached with the LOR optimized group (11.91 &mgr;g/mL [0.23–12.09 &mgr;g/mL], P = 0.065). In the LOR switched group, median IFX TL at induction (weeks 2 and 6) was significantly lower when patients had been previously exposed to anti–tumor necrosis factor compared with naive patients (0.91 &mgr;g/mL [0.12–4.4 &mgr;g/mL] versus 6.6 &mgr;g/mL [0.15–19.93 &mgr;g/mL], P = 0.044). Conclusions: This study suggests that patients who do not respond to any optimization strategy have lower IFX TLs during induction at week 6. IFX TLs measured early on at induction might predict treatment failure to IFX during maintenance.

Correction of all-trans retinoic acid deficiency in alcoholic cirrhosis lessens the excessive inflammatory monocyte response: a translational study.

Patients with alcoholic liver disease (ALD) have vitamin A (VA) deficiency and an enhanced immune response associated with disease severity. All‐trans retinoic acid (ATRA), a VA‐active metabolite, has anti‐inflammatory effects and its deficiency could contribute to the exacerbated proinflammatory reaction. The aim of this study was to investigate the effects of ATRA/VA deficiency and supplementation on the monocyte response in ALD.

Expert opinion for use of faecal calprotectin in diagnosis and monitoring of inflammatory bowel disease in daily clinical practice

Background Despite many publications regarding the role of faecal calprotectin (FC) in inflammatory bowel disease (IBD), clear recommendations for its use in clinical practice are currently lacking in the literature. Aim The aim of this article is to provide practical guidance for clinicians for the use of FC in the detection and management of patients with IBD. Methods All relevant publications were analysed and practical statements were proposed based on a Delphi consensus approach. Results Different commercial assays have been developed but international standardisation is lacking. FC can help in the diagnosis process of IBD. In IBD, FC can predict response to therapy, detect subclinical inflammation and help to drive treatment decisions to achieve better endoscopic and clinical outcomes. After Crohn’s surgery FC can identify patients with early endoscopic recurrence. Conclusion Although major therapeutic changes should not be based on FC alone, FC is a valuable tool to optimise the care for IBD patients.

Trough Levels at Induction: Impact on Long Term Response when Re-Initiating Infliximab

Infliximab (IFX) is indicated for the treatment of inflammatory bowel disease (IBD) (ulcerative colitis(UC) or Crohn disease(CD)). Nevertheless, a significant proportion of patients will experience a loss of response (LOR) to IFX over time which may require despite optimization a switch to another anti-TNF or to swap out to another biotherapy. We have recently reported that week 2 and 6 IFX through levels (TLs) can be predictive of treatment failure and long term response. Only one study has shown that week 14 TLs can be predictive of long term response on re-initiation of IFX therapy. Our objective is to evaluate early on at induction IFX TLs and antibodies to IFX (ATI) in patients previously exposed to anti-TNF. 269 IBD patients (194 CD-75 UC) have been treated with IFX on follow-up. 2331 samples were prospectively collected but measured retrospectively by ELISA in parallel with clinical data. 91 samples (TL measured <1μg/ml) were analyzed for IFX ATI using drug-sensitive bridging ELISA. At follow-up, patients were subdivided into three groups: long-term responders, patients who had LOR but responded to optimization or patients who had LOR but did not respond to optimization and were switched to another biotherapy. Each group was subdivided according to naïve or previous treatment with anti-TNF (IFX or Adalimumab) status. During induction (week 2 and 6 combined), in the LOR switched group, median IFX TL was significantly lower in previously exposed patients than in naïve patients (0.92μg/ ml[0.12-4.4μg/ml]VS6.6μg/ml[0.15-19.93μg/ml], p=0.044)(Figure 1A). Inversely, there was no statistical difference between median TL in the LOR optimized group between naïve and previously exposed patients(9.38μg/ml[0.17-14.91μg/ml]vs11.82μg/ml[0.17-14.91μg/ ml], p=0.52) as well as in naïve and previously exposed Long-term responders(9.57μg/ ml[1.44-11.97μg/ml] vs 11.91μg/ml[0.12-19.93μg/ml], p=0.92). Overall, among the previously exposed patients, the LOR switched group had a lower median IFX TL (0.92μg/ ml[0.12-4.40μg/ml]) compared to the Long-term responders(9.57μg/ml[0.44-11.97μg/ml], p=0.015) and LOR optimized group(11,82μg/ml[0.23-12.09μg/ml], p=0.005)(Figure 2). The percentage of ATI occurrence was statistically lower in the Long-term responders(5.7%) than in the LOR optimized(37.5%), p= 0.002 and LOR switched groups(40%), p=0.002. Interestingly, among the LOR switched group, the percentage of ATI occurrence was similar in patients whether naïve or previously exposed to anti-TNF (38,8%VS42,9%, p= 0.86)(Figure 1B). The same observation was found in the LOR optimized group(25%VS45% p=0.45). In LOR switched group, patients previously exposed to anti-TNF seem to have lower IFX TLs at induction (at week 2 and 6) than naïve patients. This may not be related to immunogenicity as the presence of ATI was similar in patients whether naïve or previously exposed to anti-TNF.

Sa1942 Infliximab Trough Level Measured During Treatment Induction May Be Predictive of the Loss of Response to Infliximab During Treatment Maintenance in Inflammatory Bowel Disease Patients: A Longitudinal Observational Retrospective Study

Infliximab Trough Level Measured During Treatment Induction May Be Predictive of the Loss of Response to Infliximab During Treatment Maintenance in Inflammatory Bowel Disease Patients: A Longitudinal Observational Retrospective Study Claire Liefferinckx, Charlotte Minsart, Anneline Cremer, Jean-François Toubeau, Leila Amininejad, Eric Quertinmont, André Van Gossum, Denis Franchimont, Jacques Devière