Adalimumab Drug Levels at Secondary Loss of Response Do Not Predict Response to Dose-intensification in Crohn's Disease: A Retrospective, International Multicenter Study.

BACKGROUND: The exposure-response relationship is less established for adalimumab (ADA) compared with infliximab in inflammatory bowel disease (IBD). Evidence supporting therapeutic drug monitoring post dose-intensification of ADA is limited. We aimed to explore the association between ADA drug levels and Crohn's disease (CD) activity at loss of response, and at 6 and 12 months post dose-intensification. METHODS: We performed a retrospective study of adult patients with CD receiving dose-intensified weekly ADA following secondary loss of response at 3 tertiary centers across 5 years. ADA trough levels were analyzed using a drug-sensitive enzyme-linked immunosorbent assay at loss of response, and 6 and 12 months after dose-intensification. Rates of clinical remission, objective remission (C-reactive protein <5 mg/L, fecal calprotectin <150 µg/g, or absence of inflammation at endoscopy or imaging), and ADA failure were investigated. RESULTS: A total of 131 CD patients were included, with a median disease duration of 9 (interquartile range, 4-17) years. 51% were biologic exposed prior to ADA and 50% received concomitant immunomodulators. Baseline drug levels measured at secondary loss of response did not discriminate between subsequent responders and non-responders at either 6 or 12 months post dose-intensification. However, both higher drug levels at 6 and 12 months and a higher increment from baseline were associated with improved outcomes. On receiver-operating characteristic analyses, post-escalation ADA drug levels >10.7 µg/mL (area under the receiver-operating characteristic curve [AUROC], 0.66; P = .013) and >10.9 µg/mL (AUROC, 0.67; P = .032) were associated with objective remission at 6 and 12 months, respectively. CONCLUSIONS: Drug levels following dose-intensification rather than at the time of secondary loss of response were associated with subsequent CD remission.

Literature supporting therapeutic drug monitoring at secondary loss of response and post dose-intensification of adalimumab is limited. Adalimumab drug levels following dose-intensification rather than at the time of secondary loss of response are associated with subsequent Crohn's disease remission.

Early Assessment With Gastrointestinal Ultrasound in Patients Hospitalised for a Flare of Ulcerative Colitis and Predicting the Need for Salvage Therapy: A Pilot Study.

Approximately 30% of patients hospitalised with severe ulcerative colitis do not respond to corticosteroids, but the decision to introduce salvage therapy is delayed to at least the third day of treatment, according to the widely applied Oxford criteria to assess response. This pilot study aimed to determine if gastrointestinal ultrasound performed on admission can predict steroid-refractory disease. In 10 consecutive patients with severe ulcerative colitis, gastrointestinal ultrasound was performed within 24 h of admission. Six patients failed corticosteroids and required infliximab salvage therapy. Colonic bowel wall thickness was a median of 4.6 mm (range 4.2-5.6 mm) in those responding to steroids compared with 6.2 mm (6-7.9 mm) in those requiring salvage therapy (p = 0.009). Any colonic segment with a bowel wall thickness of >6 mm was associated with the need for salvage therapy (p = 0.033). Gastrointestinal ultrasound may provide an early indication of poor corticosteroid response and enable a timelier introduction of salvage therapy in patients with severe ulcerative colitis.

Risk stratification in acute variceal bleeding: Comparison of the AIMS65 score to established upper gastrointestinal bleeding and liver disease severity risk stratification scoring systems in predicting mortality and rebleeding.

BACKGROUND AND AIM: Risk stratification is recommended in all patients with acute variceal bleeding (AVB). It remains unclear whether liver disease severity or upper gastrointestinal bleeding (UGIB) scoring algorithms offer superior predictive ability. We aimed to validate the AIMS65 score as a predictor of mortality in AVB, and to compare AIMS65 with established UGIB and liver disease severity risk stratification scores. METHODS: International Classification of Diseases, Tenth Revision codes identified patients presenting with AVB to three tertiary centers over a 48-month period. Patients were risk-stratified using AIMS65, Rockall, pre-endoscopy Rockall, Child-Pugh, Model for End-stage Liver Disease (MELD) and United Kingdom MELD (UKELD) scores. Primary outcomes were inpatient and 6-week mortality and inpatient rebleeding. RESULTS: Two hundred and twenty-three patients were included. Inpatient and 6-week mortality were 13.9% and 15.5% respectively. Prediction of inpatient mortality by AIMS65 (area under the receiver-operating characteristic curve [AUROC: 0.84]) was equivalent to UGIB (Rockall: 0.79, pre-Rockall: 0.78) and liver risk scores (MELD: 0.81, UKELD: 0.79, Child-Pugh: 0.78). AIMS65 score ≥3 best defined high- and low-risk groups for inpatient mortality (mortality 37.7% vs 4.9%). AIMS65 (AUROC: 0.62) was equivalent to UGIB risk scores (pre-Rockall: 0.64, Rockall: 0.70) in predicting inpatient rebleeding and superior to liver risk scores (MELD: 0.56, UKELD: 0.57, Child-Pugh: 0.60). CONCLUSIONS: AIMS65 is equivalent to established UGIB and liver disease severity risk stratification scores in predicting mortality, and superior to liver scores in predicting rebleeding.