Publications

BACKGROUND: With an increasing number of therapeutic options available for the management of ulcerative colitis (UC), the variability in treatment and prescribing patterns is not well known. While recent guidelines have provided updates on how these therapeutic options should be used, patterns of long-term use of these drugs over the past 2 decades remain unclear.

METHODS: We analyzed a retrospective, nationwide cohort of more than 1.7 million prescriptions for trends in prescribing behaviors and to evaluate practices suggested in guidelines relating to ordering biologics, step-up therapy, and combination therapy. The primary outcome was 30-day steroid-free remission and secondary outcomes included hospitalization, cost, and additional steroid usage. A pipeline was created to identify cohorts of patients under active UC medical management grouped by prescribing strategies to evaluate comparative outcomes between strategies. Cox proportional hazards and multivariate regression models were utilized to assess postexposure outcomes and adjust for confounders.

RESULTS: Among 6 major drug categories, we noted major baseline differences in patient characteristics at first exposure corresponding to disease activity. We noted earlier use of biologics in patient trajectories (762 days earlier relative to UC diagnosis, 2018 vs 2008; P < .001) and greater overall use of biologics over time (2.53× more in 2018 vs 2008; P < .00001) . Among biologic-naive patients, adalimumab was associated with slightly lower rates of remission compared with infliximab or vedolizumab (odds ratio, 0.92; P < .005). Comparisons of patients with early biologic initiation to patients who transitioned to biologics from 5-aminosalicylic acid suggest lower steroid consumption for early biologic initiation (-761 mg prednisone; P < .001). Combination thiopurine-biologic therapy was associated with higher odds of remission compared with biologic monotherapy (odds ratio, 1.36; P = .01).

CONCLUSIONS: As biologic drugs have become increasingly available for UC management, they have increasingly been used at earlier stages of disease management. Large-scale analyses of prescribing behaviors provide evidence supporting early use of biologics compared with step-up therapy and use of thiopurine and biologic combination therapy.

Tricyclic antidepressants (TCAs) are frequently prescribed for chronic functional pain disorders. Although the mechanism of action targets pain perception, treating patients with TCAs for disorders conceptualized as "functional" can promote stigmatization in these patients because it hints at psychological dimensions of the disorder. The goal of this study was to understand how physicians prescribe TCAs in the face of this challenge. We interviewed eleven gastroenterologists in tertiary care clinics specializing in functional gastrointestinal disorders, such as irritable bowel syndrome. We found that the physicians interviewed (1) were aware of the stigma attached to taking antidepressants for a medical condition, (2) emphasized biological, as opposed to psychological, mechanisms of action, (3) while focusing on biological mechanisms, they nevertheless prescribed TCAs in a way that is highly attentive to the psychology of expectations, making specific efforts to adjust patients' expectations to be realistic and to reframe information that would be discouraging and (4) asked patients to persist in taking TCAs despite common and, at times, uncomfortable side effects. In this context of shared decision making, physicians described nuanced understanding and behaviours necessary for treating the complexity of functional disorders and emphasized the importance of a strong patient-provider relationship.

BACKGROUND: To demonstrate treatment efficacy in Crohn's disease (CD), regulatory authorities require that trials include an endoscopic remission/response end point; however, standardized endoscopic assessment of disease activity, such as the Simple Endoscopic Score for Crohn's Disease (SES-CD), is not typically recorded by clinicians in practice or outside of clinical trials. The novel Simplified Endoscopic Mucosal Assessment for Crohn's Disease (SEMA-CD) was developed to be easy to use in routine clinical practice and as a trial end point. We conducted a study to assess and validate the reliability and feasibility of SEMA-CD as a measure of endoscopic disease activity.

METHODS: Pre- and post-treatment ileocolonoscopy videos of pediatric (n = 36) and adult (n = 74) CD patients from 2 ustekinumab clinical trials were each scored with SEMA-CD by 2 to 3 professional central readers, blinded to clinical history and other video scorings; the correlation between SEMA-CD and SES-CD previously completed during the trials was assessed. Sensitivity to change, inter- and intrarater reliability, and comparative ease of scoring were also assessed.

RESULTS: The SEMA-CD strongly correlated with SES-CD (Spearman ρ = 0.89; 95% confidence interval, 0.86-0.92). Pre- to post-treatment changes in SEMA-CD vs in SES-CD were strongly correlated, and the correlation remained strong between the scores when compared by study population (pediatric, adult), disease severity, and video quality. Intra- and inter-rater reliability were good, and SEMA-CD was rated easier than SES-CD to score 63.0% of the time, although slightly more difficult than SES-CD to score <1.0% of the time.

CONCLUSIONS: The SEMA-CD is reliable, reproducible, sensitive to change, and easy to use in both pediatric and adult patients with CD.

BACKGROUND AND AIMS: Overuse of screening colonoscopy increases cost and procedural adverse events, but inadequate surveillance can miss the development of colorectal cancer. We measured compliance with the 2020 U.S. Multi-Society Task Force on Colorectal Cancer (USMSTF) polypectomy surveillance guidelines in clinical records and a survey.

METHODS: We performed a retrospective study comparing surveillance intervals for first-time average-risk colonoscopies with the 2020 USMSTF guidelines. Cases were analyzed from 3 intervals (March 2021 to May 2021, November 2021 to January 2022, and April 2022 to May 2022), collectively termed the postguideline period, and a baseline period from November 2019 to January 2020. Real-world compliance rates were compared with results of a survey conducted between November 2020 and February 2021.

RESULTS: Overall compliance was 48.9% among 532 colonoscopies, ranging from 8.3% for low-risk adenomas (LRAs), 88.3% for high-risk adenomas, 63.1% for sessile serrated polyps (SSPs), and 88.6% for hyperplastic polyps. Compliance for LRA increased from the baseline period (.8% vs 8.3%, P = .003), and 95.3% of nonadherent LRA cases followed the 2012 USMSTF guidelines. Compliance for LRAs was 18.6% among respondents who provided a compliant surveillance interval for LRAs in the survey. Noncompliance was associated with finishing training >10 years ago (odds ratio, 1.9; 95% confidence interval, 1.4-2.7) and performing over 800 colonoscopies annually (odds ratio, 2.0; 95% confidence interval, 1.5-2.6).

CONCLUSIONS: Adoption of the 2020 USMSTF surveillance guidelines remains low at 2 years. Further research into outcomes for patients with LRAs and SSPs may increase guideline adoption.

INTRODUCTION: Medicare patients in the United States may face high out-of-pocket (OOP) costs for specialty inflammatory bowel disease (IBD) medications.

METHODS: We conducted a study of Medicare OOP costs for specialty IBD medications between 2020 and 2022 and compared them to incomes of typical Medicare beneficiaries.

RESULTS: In 2022, median OOP costs ranged from 6.4% to 59.2% of annual income for a Medicare patient with approximately median income. Inflation-adjusted OOP costs for most medications increased between 2020 and 2022 though decreased for infliximab and its biosimilars.

DISCUSSION: OOP costs may limit many Medicare beneficiaries' access to specialty IBD medications.

INTRODUCTION: We evaluated the real-world effectiveness and safety of ustekinumab (UST) in patients with Crohn's disease (CD).

METHODS: This study used a retrospective, multicenter, multinational consortium of UST-treated CD patients. Data included patient demographics, disease phenotype, disease activity, treatment history, and concomitant medications. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions were assessed using time-to-event analysis, and clinical predictors were assessed by using multivariate Cox proportional hazard analyses. Serious infections and adverse events were defined as those requiring hospitalization or treatment discontinuation.

RESULTS: A total of 1,113 patients (51.8% female, 90% prior antitumor necrosis factor exposure) were included, with a median follow-up of 386 days. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions at 12 months were 40%, 32%, 39%, and 30%, respectively. Biologic-naive patients achieved significantly higher rates of clinical and endoscopic remissions at 63% and 55%, respectively. On multivariable analyses, prior antitumor necrosis factor (hazard ratio, 0.72; 95% confidence interval, 0.49-0.99) and vedolizumab exposure (hazard ratio, 0.65; 95% confidence interval, 0.48-0.88) were independently associated with lower likelihoods of achieving endoscopic remission. In patients who experienced loss of remission, 77 of 102 (75%) underwent dose optimization, and 44 of 77 (57%) achieved clinical response. An additional 152 of 681 patients (22.3%) were dose-optimized because of primary nonresponse incomplete response to UST, of whom 40.1% (61 of 152) responded. Serious infections occurred in 3.4% of patients while other noninfectious adverse events (lymphoma [n = 1], arthralgia [n = 6], rash [n = 6], headache [n = 3], hepatitis [n = 3], hair loss [n = 3], neuropathy [n = 1], and vasculitis [n = 1]) occurred in 2.4% of patients.

DISCUSSION: UST represents a safe and effective treatment option for CD, with 40% of patients from a highly refractory cohort achieving clinical remission by 12 months. The greatest treatment effect of UST was seen in biologic-naive patients, and dose escalation may recapture clinical response.

BACKGROUND AND AIMS: The aim of this study was to assess how 6-thioguanine nucleotide (6-TGN) levels and use of oral methotrexate relate to the pharmacokinetics of biologics.

METHODS: This was a prospective cohort study including patients with inflammatory bowel diseases on maintenance doses of infliximab, vedolizumab, or ustekinumab on monotherapy or combination with a thiopurine or oral methotrexate. We collected 6-TGN concentrations, biomarker levels, and clinical and endoscopic disease activity. The primary outcomes were infliximab, vedolizumab, and ustekinumab concentrations as well as anti-drug antibodies (ADAs).

RESULTS: A total of 369 patients were recruited (113 infliximab, 133 vedolizumab, and 123 ustekinumab). Patients with 6-TGN levels ≥146 pmol per 8 × 108 red blood cells (RBCs), and those receiving combination therapy with thiopurine or oral methotrexate had significantly higher infliximab concentrations when compared with monotherapy (median levels of 17.4 μg/mL on thiopurine with 6-TGN ≥146 pmol per 8 × 108 RBCs, 17.1 on methotrexate, and 3.9 on infliximab monotherapy; P = .001 for both comparisons). However, there was no association between the use of immunomodulators and 6-TGN concentrations with vedolizumab (median levels of 8.8 on thiopurine with 6-TGN ≥152 pmol per 8 × 108 RBCs, 6.8 on methotrexate, and 10.5 on vedolizumab monotherapy; P > .05 for both comparisons) or ustekinumab median concentrations (median levels of 5.0 on thiopurine with 6-TGN ≥154 pmol per 8 × 108 RBCs, 5.2 on methotrexate and 7.0 on ustekinumab monotherapy; P > .05 for both comparisons). Fourteen (12%) patients had anti-infliximab antibodies, while 1 patient had ADAs in each of the other drug cohorts.

CONCLUSIONS: Achieving higher 6-TGN levels or the use of methotrexate improved the pharmacokinetics of infliximab. Conversely, these data do not support the use of combination therapy to augment pharmacokinetics with vedolizumab or ustekinumab.

Many patients with inflammatory bowel disease [IBD] are treated with anti-tumour necrosis factor [TNF] therapies, of which infliximab [IFX] is most commonly used. Loss of response [LOR] to anti-TNF therapy due to immunogenic failure accounts for 20% of subsequent medical intervention and is defined, using a drug-sensitive assay, as low or undetectable concentration of drug with high titres of anti-drug antibodies [ADAb]. We performed a systematic review to investigate the use of a drug-tolerant assay during both induction and maintenance, to monitor patients treated with anti-TNFs. After the search on PubMed, 90 publications were reviewed. Most ADAb detection methods are drug-sensitive, cannot detect ADAb in the presence of drug, and therefore cannot be used close to drug administration when the drug concentration is too high. To overcome this major limitation, several drug-tolerant techniques have been developed and will be discussed in this review. Using drug-tolerant assays, ADAb against IFX or adalimumab [ADM] can be detected during induction and predict primary non-response or LOR. Drug-sensitive assays do not allow detection of ADAb during the induction phase when IFX or ADM concentration is typically high.

BACKGROUND: We examined whether the difficulties of patients with somatoform disorders (SFDs) in integrating medical reassurance can be altered by preventing patients from devaluing reassuring information through defensive cognitive strategies.

METHOD: Patients with SFD (n = 60), patients with major depression (n = 32), and healthy volunteers (n = 37) watched a videotaped doctor's report, which provided medical reassurance for gastroenterological complaints. Subsequently, participants were asked about their perception of the report. In the SFD sample, patients' appraisal of the reassuring was experimentally modulated: In one condition, doubts about the validity of the doctor's diagnostic assessment were triggered; in another condition, the devaluation of medical reassurance was blocked through underscoring the validity of the doctor's diagnostic assessment; and a control condition received no manipulation.

RESULTS: As evident on all outcome variables, patients with SFD had more difficulty integrating medical reassurance than depressed and healthy people. Within the SFD sample, participants from the experimental condition blocking the devaluation of medical reassurance rated the likelihood of an undetected serious disease to be significantly lower than the other two conditions. They also reported less emotional concern and a lower desire to seek the opinion of another doctor.

CONCLUSIONS: By comparing patients with SFD to both a healthy and a clinical control group, the current study suggests that the difficulty in processing reassuring medical information is a specific psychopathological feature of SFD. Furthermore, our results suggest that the integration of medical reassurance can be improved by preventing patients from devaluing reassuring information through dismissive cognitive strategies. (PsycInfo Database Record (c) 2023 APA, all rights reserved).