Background Pivotal trials have shown that ustekinumab (UST) is effective in ulcerative colitis (UC). However, the population included in these trials do not always represent the cohort of patients treated in the “real world”. In this study, we aimed to describe the effectiveness and safety of UST in a clinical cohort of patients with UC Methods We performed a multi-center cohort study and included patients with active UC starting UST. Variables collected included demographics, previous and current UC medications, disease activity (measured using partial and endoscopic Mayo score [PMS and EMS]) at 8 weeks, 6 months and end of follow-up. We also abstracted UST drug level and anti-UST antibodies (AUA), albumin and C-reactive protein levels. Primary outcomes were clinical response at week 8 defined as a reduction of 3 points in the PMS or PMS<2. Secondary outcomes were clinical remission defined as a PMS <2 and endoscopic remission defined as a MES ≤1, and the development of an adverse event (AE) attributed to UST. Results Ninety-five patients were included with a median age of 42 years (IQR:32-57) and 53 (56%) were female. Median follow-up was 5 months (IQR:2.2-7.4). Only 4 (4.3%) were naïve to biologics or tofacitinib and 62 (66%) had previous exposure to at least 2 other biologics. No variables were found to be associated with response at week 8 (Figure 2). Those patients who responded at week 8 had higher median albumin levels vs those who did not (median of 4.4 [IQR: 4.1-4.6] vs 4.1 g/dL [IQR:3.8-4.3]; p=0.02). There were no differences in baseline CRP levels (1mg/dL [IQR:0.6-2.8] vs 0.6 mg/dL [0.3-1.5]; p=0.06). Among the 33 patients who had follow-up endoscopic assessment, 7 (21.2%) had achieved endoscopic remission and 4 (12%) achieved histologic remission. Median UST level was 4.1 mcg/ml (IQR:2.5-5.1) and no patients had detectable AUA. Five patients underwent colectomy (5.3%). Only 6 patients (6.6%) presented with an AE (all minor that included, rash, headaches, arthralgias and infection). Conclusion In a population enriched with refractory UC, UST was well tolerated and induce response and remission in a significant number of patients. The rate of response was lower in obese patients and those with extensive colitis but was not associated with previous exposure to biologics and/or tofacitinib. Larger studies with a longer follow-up are warranted. Figure 1: Rates of clinical response and remission in patients with UC receiving ustekinumab Figure 2: Association between several baseline characteristics and response to ustekinumab in UC
Background Patients with inflammatory bowel diseases (IBD) have lower bone mineral density (BMD). However, BMD does not reflect bone micro-structure/geometry, nor indicates the intrinsic properties of bone tissue. The trabecular bone score (TBS) delivers an indirect measurement of bone microarchitecture and predicts fracture risk independent of bone density. The aim of this study was to assess if patients with IBD present with lower TBS vs a healthy control (HC) population and to identify variables associated with lower TBS. Methods This prospective cohort study included patients with active Crohn’s disease (CD) or ulcerative colitis (UC) and a matched HC group. Patients with ostomies, short gut or known endocrine co-morbidities associated with low BMD, patients with osteoporosis on pharmacologic therapy were excluded. L1-L4 TBS and BMD parameters were determined by dual-energy X-ray absorptiometry (DXA) using a GE Lunar iDXA scan and TBS iNsight™ and GE enCORE™. Other collected variables included demographics, disease phenotype, laboratories (25-OH vitamin D [25OHD] and parathyroid hormone levels [PTH]), disease activity (c-reactive protein [CRP], simple endoscopic score [SES-CD] in CD, and endoscopic Mayo score [EMS] in UC). IBD severity was stratified based on endoscopy: mild (EMS=1 in UC or SES-CD=3–6), moderate (EMS=2 or SES-CD=7–15) and severe (EMS=3 or SES-CD>15). The primary outcome was the L1-L4 TBS. Secondary outcomes were left total and neck femoral BMD and the L1-L4 region BMD. Results A total of 141 patients were included (115 IBD and 26 HC). Patients with IBD had significantly lower TBS, femoral and L1-L4 BMD and Z-Scores when compared to controls (Figure 1). Endoscopic disease activity was not associated with TBS (Figure 2) or total/neck femur and L1-L4 BMD and Z-scores (p>0.05 for all). When stratifying levels by 25OHD quartiles, patients with 25OHD ≥28 ng/mL (the highest 50th percentile of the study population) had significantly higher TBS Z-scores when compared to those with 25OHD ≤28 ng/mL (0.3 [-0.2 – 1.1] vs -0.1 [-1.1 – 0.5], p=0.002). No associations were seen between TBS Z-scores and use of steroids, gender, type of IBD (UC vs CD), smoking status or when comparing females 50 years or older vs the rest of the group (p>0.05 for all). Moreover, there were no differences in TBS between patients who did or did not engage in resistance exercises (p=0.22) and/or regular aerobic exercises (RAPA ≥6) (p=0.84). Conclusion Patients with IBD present with lower TBS Z-scores when compared to HC and there is no correlation with disease activity. The only variable associated with lower TBS was a 25OHD <28 ng/mL. Further studies looking at the implications of these findings are warranted. FIGURE 1 FIGURE 2
Background The IBD Plexus® Registry, established by the US Crohn’s & Colitis Foundation, combines patient and provider reported survey data collected from doctors’ visits and historical data in electronic medical record (EMR) systems. This multi-resource dataset presents data discrepancies in assessing phenotypes of Crohn’s disease (CD). The aim of this analysis is to describe a strategic process to solve data challenges related to CD phenotype definitions based on the IBD Plexus data. Methods This cross-sectional, multicenter, US based study used data from 11/2016 to 06/2020 from the IBD Plexus® Sparc program to assess demographics, symptoms and treatments among CD patients. Data discrepancies between CD phenotype status reported and as described in historical EMRs were identified. Physicians may use the Montreal classification with/without the Paris modification for phenotype evaluation. To resolve this discrepancy, we explored and evaluated several study phenotype definitions: 1) using phenotypes at visits, the registry suggested method; 2) using phenotype and history of fistula/abscess or stricture in EMR; and 3) using definition 2 without anal stricture. The implementation included two steps: 1) severe conditions (penetrating, stricturing or both) were considered irreversible and defined using the data at any time before 30 days after the registry consent date; 2) the inflammatory condition was positive in the absence of any other reported severe condition during the entire study period. Results The frequency results by phenotypes show small differences across definitions (Figure 1). The discrepancy in frequency by definition1 demonstrated the phenotypes recorded at visits contradicted phenotypes in the EMR. For instance, 0.1%-3.2% or 0.1–0.7% of CD inflammatory patients had subtypes of stricture and subtypes of fistula/abscess, respectively. About 0.5% of CD stricturing patients had intra-abdominal abscess or other fistula (Figure 2). Among CD penetrating patients, 32.0% had history of ileal stricture (Figure 3). Including EMR phenotype variables in definition 2, all discrepancies were resolved. With verification, anal strictures are due to perianal disease which should not be used in the stricturing definition; therefore, the anal stricture was exempt from definition 3. All subtype phenotypes showed 0% discrepancy with study phenotype. A small percentage of positive anal stricture patients was allowed in definition 3. Figure 1. Figure 2. Figure 3. Figure 4. Conclusion When handling the mixture of patient reported and provider-reported data, data discrepancies have many causes. Clarifying the clinical rationale is a key process to resolve discrepancies and accurately define measures of interest.
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