Anne-Mette Haase, Jens Kelsen, Jørgen Agnholt, Mia Bendix
Calibrated logistic regression provided the best overall performance, with an internal cross-validation area under the receiver operating characteristic curve (AUROC) of 0.783 (95% confidence interval [CI], 0.755-0.809) and an external AUROC of 0.710 (95% CI, 0.600-0.820). The corresponding Brier scores were 0.180 (95% CI, 0.169-0.191) and 0.215 (95% CI, 0.170-0.263), respectively. Medication adherence was the strongest predictor of relapse, followed by fecal calprotectin, C-reactive protein and Coptidis Rhizoma dose. The learned policy increased herbal intensity with increasing fecal calprotectin and achieved a higher estimated mean reward than observed clinician behavior (0.552 ± 0.018 versus 0.063 ± 0.021). Policy-concordant visits were associated with a higher next-visit remission rate than discordant visits (70.0% versus 59.6%).
OBJECTIVE: Remission in patients with inflammatory bowel disease appears to plateau at 30-50% within the first year of biological monotherapy. Patients with Crohn's disease (CD) and ulcerative colitis (UC) on monotherapy with biologics or small molecules may face this therapeutic ceiling, not reaching remission in relation to bowel inflammation and/or extraintestinal manifestations (EIM). Dual therapy, combining two advanced therapies, has been proposed for this challenging population. We aimed to investigate real-life safety, steroid free- and clinical response in dual therapy.
MATERIALS AND METHODS: Medical records from September 2018 to September 2023 were reviewed for CD and UC patients undergoing dual therapy with biologics and/or small molecules due to refractory bowel inflammation or EIM in outpatient gastroenterology clinics at Aarhus University Hospital and Regional Hospital Randers. Patients treated for at least three months were included and followed until treatment discontinuation or the end of the study. Patient characteristics, clinical outcomes, adverse events, and clinical response data were collected at baseline and follow-up.
RESULTS AND CONCLUSIONS: Seventy-four patients (47 with CD and 27 with UC) received a total of 79 dual therapies. The median dual therapy duration was 488 days for CD and 412 days for UC. The most common combinations were adalimumab/ustekinumab in CD (46%) and adalimumab/vedolizumab in UC (35%). Clinical response at follow-up was achieved in 50% of CD patients and 45% of UC patients and steroid-free follow-up in 80% of CD patients and 52% of UC patients. Severe adverse events (SAEs) occurred in eight out of 79 dual therapies. Treatment failure and adverse events within the first three months of dual therapy were not included. This study demonstrates substantial rate of clinical response and an acceptable safety profile in complex IBD patients receiving dual therapy. Still, the risk of SAEs must be balanced against the therapeutic benefit.