Identifying Patients at High Risk of Loss of Response to Infliximab Maintenance Therapy in Paediatric Crohn’s Disease

Abstract Background 70% of patients with Crohn’s disease (CD) require intestinal resection.1 Post-operative recurrence (POR) is common with 70% of patients requiring further surgery in the pre-biologic era.2 ECCO guidelines suggest identifying patients at risk of recurrence (disease phenotype, smoking, prior resection), the use of imidazole antibiotics following surgery and assessment for recurrence within 12 months. The ECCO guidelines recommend ileocolonoscopy, although alternative modalities can be used. The Rutgeerts score predicts POR and is recommended to establish the need for preventative treatment.3 The aim of this study was to undertake a region-wide audit of practice with regards to post-operative CD in the Northern region. Methods A regional, multicentre, retrospective audit was conducted by GRANT, a network of gastroenterology trainees in Northern England. Data collection was performed for CD patients who had an ileocaecal resection between 1/9/16 and 1/9/17. Patients with an end-ileostomy were excluded. Patients were identified using clinical coding and data collection sheets were completed. Results Seven of 9 Hospital Trusts returned data. The number of eligible patients was 38 with a mean age of 41 years. Seventy-six per cent (29/38) patients had at least one risk factor rendering them ‘high-risk’ for POR (Figure 1). Only 13% (5/38) of patients received imidazole antibiotics postoperatively and only 29% (11/38) had an ileocolonoscopy within 12 months. However, 32% (12/38) had an alternative assessment of POR, with calprotectin being the most popular. An escalation in treatment following assessment was required in 25% (9/38) of patients. Postoperatively, 40% (15/38) of patients had no maintenance therapy before POR assessment; 26% (10/38) continued on the same therapy as preoperatively and34% (13/38) had augmented pre-operative therapy. Conclusion The majority of patients in Northern England who have an ileocaecal resection for CD are high risk for recurrence and many patients are not being assessed. Endoscopic POR predates clinical POR [4] and, without monitoring, the opportunity to augment therapy and prevent clinical recurrence can be missed. In Northern England, less invasive disease monitoring is being used to assess for POR and this audit would suggest that these have a comparable rate of identifying a need to escalate maintenance therapy. A postoperative CD management bundle is being developed and will be implemented to assess whether this drives improvement.

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Swapping Versus Dose Optimization in Patients Losing Response to Adalimumab With Adequate Drug Levels

Inflammatory Bowel Diseases ◽

10.1093/ibd/izab158 ◽

2021 ◽

Author(s):

Xavier Roblin ◽

Capucine Genin ◽

Stéphane Nancey ◽

Nicolas Williet ◽

Pauline Veyrard ◽

...

Keyword(s):

Ulcerative Colitis ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Maintenance Therapy ◽

Group Treatment ◽

Treatment Discontinuation ◽

Dose Optimization ◽

Secondary Loss ◽

Loss Of Response ◽

Trough Levels

Abstract Background In cases of loss of response due to mechanistic failure under antitumor necrosis factor agents, it is recommended to switch to another class of biologics. Two different strategies were compared in patients with inflammatory bowel disease (IBD) who were treated with nonoptimized adalimumab (ADA) and experienced a loss of response despite therapeutic trough levels of adalimuma—either ADA dose optimization or switching to vedolizumab or ustekinumab. Methods Patients under maintenance therapy with ADA monotherapy (40 mg every 14 days) and who experienced a secondary loss of response with trough levels > 4.9 μg/mL were included prospectively in this nonrandomized study. The primary end point was the survival rate without therapeutic discontinuation after ADA dose optimization or switching to another class of biologics. Results Adalimumab was optimized (n = 61 patients, 42 Crohn’s disease, 19 ulcerative colitis) or swapped for vedolizumab (n = 40, 20 ulcerative colitis) or ustekinumab (n = 30, 30 Crohn’s disease). At 24 months, 11 out of 70 patients (14.8%) in the swap group discontinued treatment compared with 36 out of 61 (59.6%) patients in the optimization group (P < 0.001). The median time without therapeutic discontinuation was significantly longer in the swap group (>24 months) than in the optimization group (13.3 months, P < 0.001). In the optimization group, treatment discontinuation was positively associated with baseline fecal calprotectin >500 μg/g (HR, 3.53; 95% CI, 1.16–10.72; P = 0.026) and inversely associated with variation of trough levels of adalimumab (>2 µg/mL from baseline to week 8 after optimization; HR, 0.51; 95% CI, 0.13–0.82; P = 0.03). In the swap group, no factor was associated with treatment discontinuation. Conclusion In IBD patients under ADA maintenance therapy who experience a secondary loss of response and in whom trough levels are >4.9µg/mL, swapping to another class is better than optimizing ADA, which is, however, appropriate in a subgroup of patients.

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