Background Ustekinumab (UST), an inhibitor of the p40 subunit of interleukins 12 and 23, is an effective treatment for patients with Crohn’s disease (CD) and ulcerative colitis (UC). There is limited data on therapeutic outcomes and UST trough levels (UTL). We aimed to evaluate the association between UTL and corticosteroid-free clinical remission. We also assessed the relationship between UTL and endoscopic remission as a secondary outcome. Methods We performed a cross-sectional study on IBD patients receiving maintenance therapy with UST (>6 months). We included UTL, C reactive protein (CRP), faecal calprotectin (FC), and clinical and endoscopic indexes (Harvey Bradshaw [HBI] and simple endoscopic score [SES-CD] for CD patients; and partial Mayo score [PMS] and endoscopic Mayo score [EMS] for UC patients). Corticosteroid-free clinical remission (CSF-CR) was defined as HBI<5 or PMS<2 plus normal CRP and/or FC values without corticosteroids. Endoscopic remission was defined as SES-CD<3 or EMS<2. Results We included 105 patients; the mean age was 50 years, and 59% were female (Figure 1). Eighty-seven patients had CD, and 92% had previously received an anti-TNF. The median time on UST was 121 weeks at inclusion. Sixty-four patients received 90mg subcutaneous (SC) every 4 weeks, 40 patients 90mg SC every 8 weeks, and 1 patient 90mg SC every 12 weeks. Eighty percent were in CSF-CR, and 53% were in endoscopic remission. Median UTL were 2,7µg/mL (IQR: 1,7-4,1µg/mL); UST antibodies were not detected. Patients in CSF-CR and endoscopic remission did not show significantly higher UTL (3,4µg/mL vs. 2,5µg/mL, p=0,147; and 3,6µg/mL vs. 3,7µg/mL, p=0,903, respectively). No differences in UTL were detected between patients on monotherapy and combination therapy (2,9µg/mL vs. 3,3µg/mL, p=0,456). Conclusion No association between UTL and clinical or endoscopic activity was observed in our predominantly biologic-experienced cohort. Further prospective studies are needed to determine the role of therapeutic drug monitoring while on UST.
Background Current guidelines in inflammatory bowel disease (IBD) advocate for endoscopic biopsies to confirm cytomegalovirus (CMV) colitis by means of immunohistochemistry (IHC) or tissue polymerase chain reaction (tPCR). Clinical usefulness of whole-blood PCR (bPCR) remains controversial. Our aim was to asses diagnostic accuracy of bPCR to predict CMV colitis. Methods We extracted data from all patients between 2017 and 2022 with ulcerative colitis (UC), Crohn’s disease (CD) or unclassified colitis presenting with a moderate-to-severe flare of IBD, and who were tested for CMV infection with both IHC and bPCR at the same time. IHC was considered reference standard and was used to evaluate diagnostic accuracy of bPCR. Results 89 patients were included, of which 44 (49,4%) were women, and median age was 49 years (Figure 1). 48 (50,6%) had UC, 16 (19,1%) had CD, and 25 (29,2%) had unclassified colitis. 46 (51,7%) were receiving any IBD treatment by the time of enrolment, of which 34 (67,4%) were on corticosteroids. Among patients in the CMV colitis group we found a higher proportion of leucocyte counts in the normal concentration range (p=0,035) and higher endoscopic activity using the Mayo endoscopic score in CU (p=0,027). Of the study subjects, 25 (28,2%) had CMV colitis; and bPCR was positive in 23 (25,8%). Diagnostic accuracy of bPCR was 75,3%, being sensitivity and specificity 52% and 84,4%, respectively. The positive predictive value and negative predictive value were 56,5% and 81,8%. Numerically, patients in the CMV colitis group showed higher concentrations of CMV DNA PCR without reaching statistical significance (6416,2 copies/mL vs. 2256 copies/mL, p=0,295). The area under the receiver operating characteristic curve value was 0,646 (p=0,239). When setting a threshold of above 1336 copies/mL, sensitivity and specificity values were 40% and 92,2%, respectively, and the positive likelihood ratio (LR+) was 5,13 (Figure 2). Conclusion Although bPCR showed high specificity for diagnosing CMV colitis, the sensitivity values were low. In agreement with current guidelines, blood-based tests should not replace IHC or tPCR for detecting CMV reactivation in IBD. A threshold of above 1336 copies/mL showed a moderately high LR+, thus it should prompt consideration of early antiviral treatment.
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