Supratherapeutic Infliximab Levels Do Not Predict Risk of Short-term Complications in Adults With Crohn's Disease.

BACKGROUND: It is uncertain if higher infliximab trough levels (TLs) confer a greater risk of infectious/noninfectious complications (IC/NIC). We aimed to assess the risk of IC and NIC in patients with different TLs. METHODS: We retrospectively evaluated a cohort of Crohn's disease (CD) patients treated with infliximab who underwent therapeutic drug monitoring (TDM), at a tertiary inflammatory bowel disease center, between January 1, 2010, and December 1, 2019. TDM was defined as checking of infliximab trough and antibody levels within a 48-hour period before administration. Patients with a minimum of 3-month assessment pre-TDM and post-TDM were included. In the case of multiple TDMs, the highest TL was considered, and patients were distributed across 4 predefined TL groups (A: <5 µg/mL, B: 5 to 10 µg/mL, C: 10 to 15 µg/mL, and D: ≥15 µg/mL). Rates of IC and NIC during the 3-month prior and following TDM were compared across the groups. In addition, duration of exposure, in terms of months up to TDM, was collected to analyze differences in rates of IC and NIC. RESULTS: Our study included 341 CD patients (median age: 35 y, 58% men). IC and NIC occurred in 52 (15%) and 30 (9%) patients, respectively. Rates of IC and NIC were similar across the 4 TL groups ( P =0.9 and 0.7, respectively for IC and NIC). On multivariable analysis, exposure to infliximab >40 months (as determined by receiver operating characteristic curve analysis) was associated with decreased odds for IC (adjusted odds ratio=0.51, P =0.04), but not NIC (adjusted odds ratio=0.72, P =0.46). CONCLUSIONS: In this large CD cohort, there was no association between infliximab TL and risk of short-term IC or NIC. Interestingly, a shorter duration of exposure predicted higher rates of IC. This supports the safety of targeting higher infliximab TLs when necessary and greater vigilance during the early stages of treatment.

Delineation of Crohn's Disease Trajectories Using Change in Lémann Index: A Natural History Study.

BACKGROUND: Crohn's disease (CD) causes lifelong, progressive bowel damage, which may be quantified using the Lémann Index (LI). We aimed to analyze patterns of LI and its association with 5-year clinical course, in an independent cohort of CD patients. METHODS: CD patients with 5-year follow-up from a registry maintained at a tertiary center were included. LI was calculated using a computerized metric from the first (LI1) and last (LI2) clinical encounters during the 5 years. Groups were created based on change in score (LI2-LI1) or the delta Lémann Index (DLI) as showing improvement, no change, or deterioration and used for association analysis with patterns of health care utilization, disease activity, and quality-of-life scores. RESULTS: A total of 363 CD patients with 5-year follow-up formed the study population [median age 43 y (interquartile range (IQR), 33.3 to 55 y); 57% female; median disease duration 12 y (IQR, 3 to 19 y), overall surgical exposure 69.7%]. Median (IQR) LI1, LI2, and DLI were 8 (0 to 54), 9 (0 to 75), and 0 (-22 to -47), respectively. Patients were stratified based on DLI into 3 groups: A: DLI<0; B: DLI=0; and C: DLI>0; which comprised 16.5%, 35.3%, and 48.2% of the cohort, respectively. Patients in group C had significantly higher CD-related surgical exposure, health care utilization, and annual use of steroids and biological agents. DLI showed independent significant positive correlation with perianal disease (P=0.044), steroid use (P=0.007), clinical visits (P<0.001), and new surgeries (P=0.001). CONCLUSIONS: Change in LI over time could function as a marker of disease trajectory for risk substratification and prognostication in CD.

Correlation of anemia status with worsening bowel damage as measured by Lémann Index in patients with Crohn's disease.

BACKGROUND: There is evidence that anemia in Crohn's disease (CD) is a predictor of disease severity. AIM: To evaluate if patterns of anemia over time showed correlation with aggressive disease trajectory, as characterized by change in Lémann Index (LI), which is a metric that quantifies bowel damage. METHODS: CD patients with 5 year (y) follow-up from a prospective registry were included. LI was calculated from the first (LI1) and last (LI2) clinical encounters. The change in score (LI2-LI1) or the Delta LI (DLI) was recorded. Patterns of anemia, healthcare utilization and disease activity scores were analyzed. RESULTS: A total of 389 CD patients with 5y follow-up formed the study population [median age 40y (IQR: 31-53); 57.3% female; median disease duration 12y (IQR: 6-20.5), overall surgical exposure 69%]. Patients with anemia had significantly higher LI1, LI2, DLI and also significantly higher healthcare utilization and indices of disease activity, than patients without anemia (p<0.001). CD patients with anemia for any duration during the study had OR of 2.15 (95% CI 1.29-3.57, p=0.003) for worsening bowel damage over the 5y. CONCLUSION: Based on a longitudinal analysis of CD patients, anemia status over time shows significant correlation with increasing Lémann index and aggressive disease trajectory.

Acute disseminated encephalomyelitis following seasonal influenza vaccination in an elderly patient.

Although such occurrences are rare, it should be recognized that certain vaccines might trigger serious neurological immune phenomena such as Guillain-Barre syndrome, seizures, cranial neuropathy, and acute disseminated encephalomyelitis (ADEM). Here we report on an elderly woman with ADEM following seasonal influenza vaccination who recovered after plasma exchange.