Background Therapeutic drug monitoring (TDM) is a diagnostic tool in the monitoring of anti-TNF therapies. Yet, the benefit for TDM of new biologics such as ustekinumab (USK) is still controversial in real-world experiences. Methods This monocentric retrospective study aims to correlate USK trough levels (TLs) with clinical and endoscopic data. All patients have given written consent to the Biobank (B2011/005). Endoscopic disease was defined as quiescent in absence of endoscopic lesions, mild disease in presence of few superficial ulcerations, moderate in presence of several ulcers and severe in presence of numerous deep ulcers and/or inflammatory stenosis. 313 serum USK samples from 67 Crohn’s disease patients were used to measure USK TL (USK ELISA, apDia) while 88 samples (at week 16, and before and after optimisation) were used to measure anti-drug antibody (ADA), using a drug-tolerant affinity capture elution anti-ustekinumab assay Results Demographic and baseline data of our population are presented in Table 1. The median follow-up was 73 weeks (IQR 39–92). An optimisation due to loss of response was required in 44.8% of patients (n = 30) after a median time of 38 weeks (IQR 24–55). To evaluate the drug efficacy, an endoscopy was performed in 61% of cases at a median time of 35 weeks (IQR 27–47). TLs were 5.2 µg/ml (IQR 2.1–8.8), 1.7 µg/ml (IQR 0.3–4.3) and 2.6 µg/ml (IQR 0.6–4.1) at week 8, 16 and 24, respectively. TLs at week 8 were correlated to the induction IV dose administrated (r = 0.3, p = 0.03). At week 16, low TLs were associated with higher endoscopic activity in the follow-up (p = 0.02), although this was not the case at week 8 (p = 0.5) (Figure 1). Patients not requiring an optimisation had higher TLs in maintenance than patients requiring optimisation (2.45 µg/ml (IQR 1.3–4.4) vs. 1.15 µg/ml (IQR 0.1–2.24), p = 0.008). Obviously, optimisation significantly increased TLs (1.15 µg/ml (IQR 0.1–2.24) vs. 6.6 µg/ml (IQR 2.3–11.3), p < 0.001). ADA were undetectable in all the measured samples in maintenance. Conclusion This real-world experience confirms a drug exposure-endoscopic response relationship. Week 16 seems to be an appropriate time point to monitor drug exposure. Earlier USK TLs, at week 8, appear less valuable to be monitored due to the influence of initial IV dose. The absence of immunogenicity suggests that it is not a key driver in the loss of response.

Background In addition to physical and psychological factors, systemic inflammation, anaemia and/or malnutrition contribute to fatigue in Crohn’s disease (CD) and ulcerative colitis (UC). Despite recent advances in the management of the disease activity, fatigue is a major disabling symptom for inflammatory bowel disease (IBD) patients. Methods The aim of this prospective study is to evaluate the prevalence of IBD patients suffering from fatigue in a tertiary IBD referral centre and delineate its contributing factors. All patients with a confirmed IBD diagnosis were eligible. A given written consent has been obtained for each patient (P2019/053). Fatigue evaluation was assessed by FACIT-F. Self-report questionnaires were used to assess different factors related to fatigue: disease activity was assessed by patient-reported outcomes (PRO), anxiety by State and Trait Spielberger scores, depression by Beck score (BDI-II), sleep quality by Insomnia severity index (ISI) and Epworth scale, and quality of life by the Short Inflammatory Bowel Disease Questionnaire (SIBDQ). Biological values including haemoglobin, C-reactive protein (CRP), thyroid-stimulating hormone (TSH), folic acid and B12 vitamin were collected when available. Results Demographic data of the 128 included patients are presented in Table 1. This cohort was characterised by a high prevalence of CD complicated behaviours and UC pancolitis. 84.4% of patients (n = 108) were exposed to biologics at the time of completion of the questionnaire. The prevalence of fatigue was 65.6% stratified as severe (FACIT-F <20) and moderate (FACIT-F 20–40) in 21.1% and 44.5%, respectively. Fatigue was clearly associated with active disease in CD, anxiety, depression, poor quality of life, insomnia and somnolence but not with active disease in UC. All biological values were within normal ranges and did not influence fatigue. Older age at diagnosis was associated with lower FACIT-F score while disease duration was not (Table 2). No correlation was found between fatigue and any specific biologics (p = 0.08). Conclusion This prospective study reported a fatigue prevalence of 65.6% in a severe IBD cohort highly exposed to biologics. Beyond disease activity in CD, psychological factors (whether they are causes or consequences) such as anxiety, depression, poor quality of life and insomnia were associated with fatigue.