Prospective Evaluation of Serum Free Thiols in Inflammatory Bowel Disease: A Candidate to Replace C-Reactive Protein for Disease Activity Assessment?

BACKGROUND: Serum free thiols (SFTs) reflecting oxidative stress appear to correlate with inflammatory bowel disease (IBD) activity. We aimed to evaluate the performance of SFTs concentrations vs endoscopic and histological activity, compare SFTs with established biomarkers, and identify clinical and laboratory parameters independently associated with SFT levels in IBD patients. METHODS: Patients with confirmed IBD undergoing routine ileocolonoscopy for activity assessment were prospectively recruited, with serum samples obtained concurrently for SFTs and routine bloods, plus fecal calprotectin and immunochemical tests were collected ±30 days from ileocolonoscopy. Endoscopic activity was assessed via established indices and histological activity graded as inactive/mild/moderate. Receiver-operating characteristic curve analyses were utilized to assess performance of SFTs vs endoscopic activity, and multiple regression analysis was used to identify factors associated with SFT levels. RESULTS: A total of 141 (80 Crohn's disease, 61 ulcerative colitis) patients were recruited. Median SFTs were significantly lower in moderate vs inactive/mild endoscopic activity (309 µM vs 433/471 µM, respectively; P < .01). There was no significant difference in median SFTs across inactive/mild/moderate histological activity. SFTs achieved higher sensitivity than C-reactive protein in predicting moderate, endoscopically active disease (89% vs 78%; area under the curve, 0.80 each) yet was outperformed by fecal calprotectin (100%; area under the curve, 0.93). Advancing age and increasing albumin levels were independently associated with SFT levels, and thus are possible confounders. CONCLUSIONS: This prospective study has demonstrated the potential of SFTs as a serum biomarker in IBD. It was more sensitive than C-reactive protein, yet less sensitive than fecal biomarkers for prediction of endoscopically active IBD.

The synergy of dual faecal immunochemical and faecal calprotectin testing for accurate assessment of endoscopic and histological activity in inflammatory bowel disease.

Background: Faecal biomarkers are increasingly utilized for disease assessment in inflammatory bowel disease (IBD). Objectives: To characterize the relative and combined accuracy of faecal calprotectin (FC) and faecal immunochemical testing (FIT) for detecting endoscopic and histologically active disease in Crohn's disease (CD) and ulcerative colitis (UC), subdivided by disease location. Design: A prospective cohort study. Methods: Patients with confirmed IBD undergoing routine ileocolonoscopy for activity assessment were prospectively recruited and performed both FC and FIT ±30 days of ileocolonoscopy. Endoscopic activity was assessed via the simplified endoscopic score for CD, Mayo endoscopic score for UC and histological activity graded as nil/mild/moderate. Receiver-operator curve analyses were utilized to assess the performance of FC and FIT per disease subtype and location. Results: In all, 137 (79 CD, 57 UC) patients were recruited. FC was more sensitive than FIT in detecting active endoscopic (CD: 91% versus 69%, UC: 94% versus 82%) and histological (CD: 86% versus 55%, UC 88% versus 56%) disease. However, FIT was more specific than FC in detecting active endoscopic (CD: 94% versus 56%, UC: 85% versus 69%) and histological (CD: 93% versus 55%, UC: 96% versus 70%) diseases. FIT was more sensitive and specific than FC in detecting active colonic CD (endoscopic activity: 94% versus 93%, histological activity: 92% versus 77%, respectively); however, it was poorly sensitive for active ileal CD (43% versus 89%). Conclusion: FC demonstrated higher sensitivity and FIT higher specificity for active IBD. Hence, dual testing was synergistic, displaying excellent performance characteristics across most IBD locations and subtypes, holding promise for future clinical application. Trial registration: Not applicable.

Therapeutic Drug Monitoring for Biologic and Small-Molecule Therapies for Inflammatory Bowel Disease.

Background: Inflammatory bowel disease (IBD), encompassing ulcerative colitis and Crohn's disease, necessitates long-term medical therapy to manage symptoms and prevent complications. Therapeutic drug monitoring (TDM) has emerged as a strategy to optimize treatment efficacy, particularly with anti-tumour necrosis factor (anti-TNF) alpha drugs. This review explores the role of TDM for non-anti-TNF advanced therapies in IBD, focusing on vedolizumab, ustekinumab, tofacitinib, upadacitinib, risankizumab and ozanimod. Methods: The literature search, conducted through OVID (Medline) and PubMed, delves into proactive versus reactive TDM, timing of monitoring and methods for measuring drug levels and anti-drug antibodies. Results: While ustekinumab and vedolizumab exhibit exposure-response relationships, consensus on target levels and the role of TDM adjustments remains elusive. Limited data on risankizumab suggest a dose-dependent response, while for small molecule therapies (janus kinase inhibitors and ozanimod), the absence of real-world data and commercially available TDM tools pose challenges. Conclusion: At present, with the available data, there is a limited role for TDM in non-anti-TNF biologic and small-molecule therapies. This review underscores the need for further research to delineate the utility of TDM in guiding treatment decisions for these agents.

The Nocebo Effect in a Non-Medical Switching Program from Originator to Biosimilar Infliximab in Inflammatory Bowel Disease.

BACKGROUND: Despite growing awareness of the nocebo effect, few studies have evaluated the nocebo effect using combined assessment of patient-reported outcome measures (PROMs), clinical indices, and objective biomarkers in inflammatory bowel disease (IBD) patients switching from originator to biosimilar medicines. OBJECTIVE: This study aimed to compare these outcomes across switch and non-switch cohorts to evaluate the nocebo effect in patients with IBD. METHODS: Parallel cohorts of IBD patients who (1) switched from originator to biosimilar (CT-P13) infliximab and (2) continued biosimilar (CT-P13) infliximab were evaluated over 32 weeks. Clinical disease activity, objective biomarkers and PROMs were assessed at baseline, and weeks 16 and 32 across both cohorts. The PROM of interest was patient-perceived disease activity evaluated using a 0-100 visual analogue scale (VAS) per the IBD-Control Questionnaire. RESULTS: Of 81 patients, 47 switched from originator to biosimilar (CT-P13) infliximab. A negative change from baseline patient-reported disease control was observed across the switch cohort compared with the non-switch cohort at week 16 (mean VAS - 8.21 vs. 1.26; p = 0.03), but not at week 32 (mean VAS - 1.21 vs. 1.38; p = 0.58). Corresponding clinical and objective biomarker assessments over these timepoints were comparable across both cohorts. CONCLUSION: This study demonstrated a temporary yet discernible nocebo effect in the first 16 weeks following non-medical switching that was not sustained at week 32. Negative patient perceptions may be overcome by a patient-inclusive approach to non-medical switching in conjunction with close clinical follow-up and disease monitoring.

Testing for HIV among men who have sex with men needs a paradigm shift in Australia, given the minimal increase between 2003 and 2013 in Melbourne, Australia.

UNLABELLED: Background Increasing the frequency of HIV testing in men who have sex with men (MSM) will reduce the incidence of HIV. Trends in HIV testing among MSM in Melbourne, Australia over the last 11 years have been investigated. METHODS: A retrospective study was conducted using electronic medical records of the first presentation of MSM who attended the Melbourne Sexual Health Centre between 2003 and 2013. Factors associated with HIV testing (year, demographic characteristics and sexual practices) were examined in multivariable logistic regression analyses. Jonckheere-Terpstra tests were used to examine the significance of trends in the mean time since the last HIV test. RESULTS: Of 17578 MSM seen; 13489 attended for the first time during the study period. The proportion of first attendances who had previously tested and reported a HIV test in the last 12 months increased from 43.6% in 2003 to 56.9% in 2013 (adjusted ptrend=0.030), with a corresponding decrease in median time since the last HIV test from 19 months [interquartile range (IQR) 6-42] in 2003 to 10 months (IQR4-24) in 2013 (ptrend <0.001). The proportion of high-risk MSM (who reported unprotected anal intercourse and/or >20 partners in 12 months) who reported an HIV test in the last 12 months was unchanged (ptrend = 0.242). CONCLUSIONS: Despite HIV testing becoming more frequent, the magnitude of change over the last decade is insufficient to substantially reduce HIV incidence. A paradigm shift is required to remove barriers to testing through strategies such as point-of-care rapid testing or access to testing without seeing a clinician.

High prevalence of rectal gonorrhoea among men reporting contact with men with gonorrhoea: Implications for epidemiological treatment.

BACKGROUND: This study aimed to determine the prevalence of gonorrhoea and factors associated with rectal gonorrhoea among men reporting sexual contact with men with gonorrhoea. METHODS: Men who presented to Melbourne Sexual Health Centre reporting sexual contact with a male with gonorrhoea were prospectively identified between March 2011 and December 2013. These men were screened for pharyngeal and rectal gonorrhoea using culture. The prevalence of gonorrhoea among contacts was compared to that among all men who have sex with men (MSM) screened at the clinic over the same period. RESULTS: Among 363 contacts of gonorrhoea the prevalence of rectal gonorrhoea was 26.4% (95% CI: 21.8%-31.0%) compared to 3.9% (95% CI: 3.7%-4.2%) among clinic attendees (p < 0.001). The prevalence of pharyngeal gonorrhoea among contacts was 9.4% (95% CI: 6.4%-12.4%) compared to 2.1% (95% CI: 1.9%-2.4%) among clinic attendees (p < 0.001). Among contacts who reported not always using condoms during receptive anal sex with casual partners, rectal gonorrhoea was cultured in 42.4% compared with 12.7% among contacts reporting no receptive anal sex (p < 0.001) and 20.2% among those reporting always using condoms (p < 0.001). On multivariate analysis rectal gonorrhoea was associated with inconsistent condom use during receptive anal sex with casual partners (adjusted odds ratio (AOR): 4.16; 95% CI: 1.87-9.26) and a reported past history of gonorrhoea (AOR: 1.77; 95% CI: 1.01-3.14). CONCLUSIONS: The high proportion of positive cases of gonorrhoea among contacts in this study supports epidemiological treatment of MSM presenting as contacts of gonorrhoea.