Citations

Abstract Background Hospital readmissions pose a challenge for modern healthcare systems. Our aim was to assess the efficacy of telemedicine incorporating telemonitoring technologies in decreasing hospital readmissions with a focus on specific patient populations particularly prone to rehospitalization: patients with heart failure (HF) and/ or chronic obstructive pulmonary disease (COPD) through a systematic review. Methods Three major electronic databases, including PubMed, Scopus, and ProQuest’s ABI (Abstracted Business Information)/INFORM Global, were searched for trials employing telemedical technologies and quantifying the effect on the readmission rates in the HF and/or COPD populations. Our search was limited to English-language articles published between 2012 and 2022. Results Eighteen scientific articles referencing seventeen different clinical trials were isolated. Most studies were randomized controlled trials and the readmission related outcome most studied was all-cause readmissions followed by HF and acute exacerbation of COPD readmissions. 47% of the studies suggested that telemedicine might decrease the readmission related burden, while most of the remaining studies suggested that telemedicine had a neutral effect on hospital readmissions. Comparative analysis of studies focusing on the COPD or HF populations resulted in the observation of a clearer association in the reduction of the readmission-related burden in patients with COPD compared to patients with HF (83% vs 27%). Data regarding other relevant outcomes often assessed including all-cause mortality emergency department visits, healthcare costs, quality of life, medication adherence and reconciliation were extracted and qualitatively assessed. Conclusion This systematic review highlights the uncertainty surrounding the effectiveness of telemedicine in reducing the readmission rates of high-risk patients with chronic illnesses, with much of the uncertainty linked to the variability of the deliverable of telemedicine. Nonetheless, the fact that almost all trials found that patients receiving telemedicine benefited to some extent and the strong association in the reduction of readmissions in the COPD population are encouraging. Conduction of more high-quality studies is necessary to draw definitive conclusions.

Abstract Background Ulcerative colitis (UC) has a detrimental impact on patients’ health-related quality of life (HRQoL).1 Long-term treatment goals for patients with moderately to severely active UC include restoration of HRQoL. This post-hoc analysis evaluated the effect of induction and maintenance treatment with risankizumab (RZB) on HRQoL outcomes. Methods Data from two Phase 2b/3 clinical trials (INSPIRE induction: NCT03398148 and COMMAND maintenance: NCT03398135) were evaluated. Patients received RZB 1200 mg intravenous (IV) or placebo (PBO) induction treatment at weeks 0, 4, and 8. Patients with a clinical response per Adapted Mayo score to RZB IV were randomised 1:1:1 to subcutaneous (SC) RZB 180 or 360 mg, or placebo (PBO [RZB withdrawal] SC) every 8 weeks for 52 weeks of maintenance. The proportion of patients achieving a meaningful within-person change (MWPC) for each HRQoL outcome was reported. HRQoL outcomes included Functional Assessment of Chronic Illness Therapy-Fatigue, disease-specific instruments such as Inflammatory Bowel Disease Questionnaire (IBDQ) and Ulcerative Colitis Symptom Questionnaire (UCSQ), as well as generic quality-of-life questionnaires like Work Productivity and Activity Index-Ulcerative Colitis (WPAI-UC), 36-Item Short-Form Survey (SF-36), and EuroQoL 5 Dimensions 5 Levels. MWPCs were measured from baseline to induction Week 12 and to maintenance Week 52. Estimated differences in proportions with 95% confidence intervals and p-values between RZB and PBO were compared using the Cochran-Mantel-Haenszel test adjusting for baseline strata. Results For RZB 1200 mg IV (n=650) versus PBO IV-treated (n=325) patients, a greater proportion of patients achieved MWPC across all HRQoL outcomes at Week 12 of induction (p<0.01; Table). At Week 52 of maintenance, a greater proportion of patients treated with RZB 180 mg SC (N=179) versus PBO (withdrawal) SC (N=183) achieved MWPC across all HRQoL outcomes (p<0.05), except for absenteeism from WPAI-UC (p=0.33). For RZB 360 mg SC (N=186) versus PBO (withdrawal) SC, a greater proportion of patients achieved MWPC for UCSQ, IBDQ, and SF-36 physical component summary (all p<0.05). Conclusion In this analysis, a greater proportion of patients treated with RZB versus PBO achieved MWPC on various HRQoL outcomes after completing 12-week induction IV therapy. HRQoL improvements were sustained up to Week 52 of treatment. This suggests RZB has the potential to help patients achieve restoration of HRQoL as a long-term goal of treatment in patients with moderately to severely active UC. 1. Mavroudis G. Therap Adv Gastroenterol. 2022;15:17562848211062406.

Abstract Background The LIBERTY-CD study demonstrated a broad level of benefit for subcutaneous (SC) infliximab (IFX) maintenance therapy compared with placebo in patients (pts) with moderate-to-severe active Crohn’s disease (CD) who responded to intravenous IFX induction. Characterising subgroups of pts with different levels of response could help to better position SC IFX therapy. Methods This was a post hoc analysis of 231 pts from the CT-P13 SC arm of the randomised, parallel-group, placebo-controlled LIBERTY-CD study (NCT03945019). Unsupervised group-based trajectory modelling (GBTM) was conducted to deconvolute cohort-level data into response trajectories. Longitudinal patient reported outcomes (PRO-2: abdominal pain and stool frequency) were used to investigate whether pts who received SC IFX maintenance therapy cluster into response trajectories. Efficacy endpoints (clinical remission, endoscopic response and remission, corticosteroid-free remission and comprehensive disease control [CDC] rate) were analysed and compared between different trajectories. Trough levels of IFX (TLI) were evaluated by trajectory throughout the treatment period. Baseline characteristics were analysed in a descriptive manner to explore predictors for super-response. Results Four distinct trajectories were clearly separated and stabilised around Week (W) 10–14 (Figure): rapid and sustained improvement (super-responders, n=61), rapid, but slightly less drastic than super-responders, then sustained improvement (fast responders, n=56), gradual then sustained improvement (slow responders, n=63) and partial improvement during the maintenance phase (limited responders, n=51). Super-responders had the highest rates of W54 clinical remission (73.8%; p=0.002), endoscopic response (63.9%; p=0.009), corticosteroid-free remission (63.6%; p=0.007), endoscopic remission (42.6%; p=0.094) and CDC (37.7%; p=0.013) among trajectories (Table). Super-responders also maintained the highest TLI from W10 throughout the maintenance period. Super-responders showed a trend towards lower baseline body weight, body mass index and oral corticosteroid use, but higher Crohn’s Disease Activity Index score and prior biologic/Janus kinase inhibitor use compared to other trajectories. Conclusion Distinct subpopulations with different levels of responses were detected by GBTM using data from a large group of pts with moderate-to-severe active CD who were treated with SC IFX for 1 year. Super-responders with rapid and sustained improvements during SC IFX therapy had a higher likelihood of achieving desirable long-term outcomes, with substantial individual benefit (CDC). Baseline characteristics and TLI were associated with super-response.

Abstract Background Etrasimod is an oral, once-daily (QD), selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). Previous work has shown age can impact treatment safety and efficacy in patients with inflammatory bowel disease.1 This post hoc analysis investigated the impact of age on the safety and efficacy of etrasimod in patients with UC in the phase 3 ELEVATE UC clinical programme. Methods Data pooled from the ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369) trials were analysed in patients receiving etrasimod 2 mg QD and placebo. ELEVATE UC 52 had a treat-through design comprising a 12-week induction period followed by a 40-week maintenance period. ELEVATE UC 12 was a 12-week induction trial. Proportions and incidence rates (IRs) per 100 patient-years from pooled data of treatment-emergent adverse events (TEAEs) and events of interest were stratified by age (<40 years, 40–59 years, ≥60 years) and analysed in patients who received ≥1 dose of etrasimod or placebo. Efficacy analyses were evaluated in patients with baseline Modified Mayo score (MMS) 5–9 for the primary efficacy endpoint (clinical remission) and select secondary endpoints at Week 12 (both trials) and Week 52 (ELEVATE UC 52) stratified by age. Results There were 787 patients enrolled in the ELEVATE UC programme, of whom 420 (53.4%) were aged <40 years, 276 (35.1%) were aged 40–59 years and 91 (11.6%) were aged ≥60 years. The proportions and IRs of TEAEs and events of interest were mostly similar between age groups and treatment arms (Table). IRs of arthralgia, fatigue, hypertension and pyrexia were higher in older age groups, regardless of treatment arm. Serious AEs and AEs leading to treatment discontinuation were low and consistent across all age subgroups. Serious infections and infection events of interest were balanced across age groups and treatment arms. Regardless of age subgroup, significantly more patients treated with etrasimod 2 mg QD vs placebo achieved the primary and select secondary efficacy endpoints at Week 12 and Week 52 (Figure). Conclusion The safety profile of etrasimod 2 mg QD in the UC population was consistent across age groups, and with no new risks other than the estimated risks associated with increasing age.2 Patients receiving etrasimod in the ELEVATE UC programme showed significant clinical benefit as assessed by clinical remission, symptomatic remission and endoscopic improvement compared with placebo, regardless of age. References 1. Lichtenstein GR et al. Inflamm Bowel Dis 2023; 29: 27–41. 2. Luo J et al. JMIR Med Inform 2016; 4: e30.

Abstract Background Filgotinib (FIL), an oral, once-daily, Janus kinase 1 inhibitor, was approved for Ulcerative Colitis (UC) treatment after the phase 2b/3 SELECTION trial (NCT02914522). In SELECTION, a greater proportion of FIL200 mg (FIL200)-treated than placebo-treated patients achieved comprehensive disease control (CDC), a stringent multi-component endpoint. We examined the long-term outcomes of achieving CDC in patients continuing on FIL200 in the ongoing long-term extension (LTE) study SELECTIONLTE (NCT02914535). Methods This interim analysis included adult patients with UC who completed SELECTION and received ≤144 weeks of FIL200 in the LTE (up to data cut-off 24/02/22). CDC (biomarker remission, endoscopic improvement, IBDQ remission and partial Mayo Clinic Score [pMCS] remission achieved concurrently) was assessed at SELECTION week 58 (LTE baseline [BL]). Mean pMCS and IBDQ score, use of corticosteroids (CS) and incidence of TEAEs and serious TEAEs in the LTE were compared between SELECTION CDC achievers and non-achievers. A mixed model for repeated measures was fitted on pMCS and IBDQ score, with CDC achiever status, study visit and the interaction between CDC achiever status and study visit as fixed effects; p values were nominal. Results We analysed 148 patients (CDC achievers, n=41; CDC non-achievers, n=107). Mean pMCS was stable in CDC achievers (0.44, LTE BL; 0.50, LTE week 144) and decreased in CDC non-achievers (1.49, LTE BL; 0.77, LTE week 144; Figure). Mean IBDQ score was stable in CDC achievers (204.05, LTE BL; 197.21, LTE week 144) and increased in CDC non-achievers (181.55, LTE BL; 196.37, LTE week 144; Figure). There was a significant beneficial effect of achieving CDC on pMCS and IBDQ score overall (pMCS: fixed effect estimate: −0.5542, p=0.0025; IBDQ score: fixed effect estimate: 13.1585, p=0.0042). There was a significant interaction between achieving CDC and study visit for IBDQ score (p=0.0183), with the benefit of achieving CDC lessening by week 144. Generally, a lower proportion of CDC achievers used CS than non-achievers; 2.4–7.3% of CDC achievers used CS vs 1.9–15.9% of CDC non-achievers. Incidence of TEAEs and serious TEAEs were stable over time and similar between CDC achievers and non-achievers. Conclusion Follow-up for ~3 years showed high levels of long-term benefit with continued FIL200 treatment. Achieving comprehensive disease control at the end of the randomized trial with FIL200 was associated with long-term efficacy, improved HRQoL and low overall use of CS. This may demonstrate the value of filgotinib-induced achievement of CDC in UC disease course. The safety profile of FIL200 was consistent between CDC achievers and non-achievers, suggesting an acceptable long-term benefit–risk profile.

Abstract Background Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). Adverse events (AEs) pertaining to tolerability, laboratory and serious AEs are described elsewhere1,2; we present a post hoc analysis of the incidence, onset and duration of the most commonly occurring non-serious AEs in the etrasimod UC clinical programme. Methods Data from the pooled Placebo-controlled UC cohort, derived from the phase 2 OASIS (NCT02447302) and phase 3 ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369) double-blind clinical trials, were included. Cohorts comprised OASIS and ELEVATE UC 12 12-week induction periods alongside the ELEVATE UC 52 12-week induction and 40-week maintenance periods utilising a "treat-through" design. Patients (pts) with moderately to severely active UC were eligible for the etrasimod UC clinical programme. Pts were randomised to etrasimod 1 mg once daily (QD; OASIS only), etrasimod 2 mg QD or placebo. Proportions and incidence rates (IRs) of non-serious AEs (MedDRA v24.1 Preferred Terms of headache, pyrexia, nausea, fatigue and dizziness) were analysed in the Placebo-controlled UC cohort. Results Among 943 pts (any dose of etrasimod, N=629 [288.1 pt years (PY)]; placebo, N=314 [115.1 PY]), there were 77, 36, 30, 15 and 23 headache, pyrexia, nausea, fatigue and dizziness AEs, respectively. All were non-serious and did not lead to treatment discontinuation, apart from one case of pyrexia in which early termination visits were incomplete. Proportions and IRs (per 100 PY) for headache and dizziness AEs were higher with etrasimod (any dose) vs placebo (IRs: 13.45 vs 8.63 and 6.52 vs 1.69, respectively); IRs for other non-serious AEs were similar in etrasimod (any dose) and placebo groups (Table). Onset of AEs varied over time and most AEs were short in duration (Figure shows onset and duration for headache and dizziness AEs). Most AEs were deemed not related to study treatment by the site investigator. Pts with dizziness on Days 1–3 had similar changes in heart rate vs those with dizziness after Day 3. No consistent trend in heart rate was observed in pts receiving etrasimod with early dizziness. Conclusion Among pts in the etrasimod UC clinical programme, all headache, pyrexia, nausea, fatigue and dizziness events were non-serious. IRs were similar for most non-serious AEs across treatment groups, excluding headache and dizziness. Most non-serious AEs were short in duration and judged as not related to study treatment, suggesting they may not impact on the overall tolerability of etrasimod. References 1. Sandborn WJ et al. Gastroenterology 2020; 158: 550–61. 2. Sandborn WJ et al. Lancet 2023; 401: 1159–71.

Abstract Background Upadacitinib (UPA) is an oral Janus kinase inhibitor approved for the treatment of moderately to severely active Crohn’s disease (CD).1 The U-ENDURE (NCT03345823) maintenance study and long-term extension (LTE) evaluate the long-term efficacy and safety of UPA maintenance therapy. Here, we report the results of the U-ENDURE LTE. Methods Patients (pts) completing the U-ENDURE 52-week (wk) maintenance study were eligible to participate in the LTE and continue their previously assigned treatment (placebo [PBO], UPA 15 mg [UPA15] once daily [QD], or UPA 30 mg [UPA30] QD; blinded until the last pt completed maintenance wk52). Clinical response, clinical remission, endoscopic response, endoscopic remission, as well as high-sensitivity C-reactive protein (hs-CRP) and faecal calprotectin (FCP) were evaluated as-observed up to wk48 of the LTE among pts (PBO [N = 89], UPA15 [N = 107], UPA30 [N = 173]); excluding pts who received open-label UPA30 rescue therapy. Safety was assessed in all pts (PBO [N = 223], UPA15 [N = 221], UPA30 [N = 229]) from wk0 of the maintenance study up to LTE wk204 (cut-off date: 01 Aug 2023). Results At LTE wk0, the SF/APS clinical remission rates were 73.0%, 78.3%, and 80.3% for PBO, UPA15, and UPA30, respectively (Figure 1A). Similar rates were reported at LTE wk0 for CDAI clinical remission (PBO 75.3%, UPA15 81.3%, UPA30 80.9%; Figure 1B) and clinical response (CR-100: PBO 79.5%, UPA15 84.9%, UPA30 84.4%). Rates of clinical remission were stable through wk48 of the LTE. Endoscopic response (PBO 32.9%, UPA15 59.6%, UPA30 66.5%) and remission rates (PBO 27.8%, UPA15 42.4%, UPA30 47.3%) at LTE wk0 were sustained through wk48 with UPA while decreased with PBO (Figure 1C-D). At LTE wk0, the mean [95% CI] change from induction BL in hs-CRP was 1.8 [–0.4, 4.1], –13.2 [–17.9, –8.6], and –12.8 [–16.8, –8.9] for PBO, UPA15, and UPA30, respectively; sustained through wk48. Similar results were observed with FCP (mean [95% CI] change from induction BL: PBO 126 [–103, 356], UPA15 –2946 [–4121, –1772], UPA30 –1871 [–2577, –1165]). Severe adverse events (AEs) and serious AEs were lower with UPA treatment compared with PBO (Table 1). The rates of most AEs of special interest were similar between UPA and PBO; however, numerically higher rates of herpes zoster, adjudicated gastrointestinal perforations, neutropenia, lymphopenia, creatine phosphokinase elevation, and hepatic disorders were reported in pts treated with UPA vs PBO (Table 1). Conclusion In pts completing wk48 of the LTE, sustained efficacy was observed in clinical and endoscopic endpoints with over 2 years of UPA treatment, while maintaining an overall positive safety profile in pts with CD. Reference: 1. Loftus EV Jr, et al. N Engl J Med. 2023;388:1966–80

Abstract Background Risankizumab (RZB), a monoclonal antibody targeting interleukin-23 p19, was evaluated for maintenance therapy in patients with moderately to severely active ulcerative colitis (UC) and clinical response to RZB intravenous (IV) induction treatment in a phase 3 double-blind, placebo (PBO)-controlled withdrawal (WD) maintenance study, COMMAND (NCT03398135). Methods Patients with moderately to severely active UC who achieved a clinical response per Adapted Mayo score after 12 or 24 weeks (wks) of RZB IV treatment in the phase 2b and phase 3 INSPIRE induction studies (NCT03398148)1 were randomized 1:1:1 in COMMAND to RZB 180 mg (RZB180), 360 mg (RZB360), or PBO (RZB withdrawal) subcutaneous (SC) treatment every 8 wks for 52 wks. The efficacy analysis included responders to 12 wk of RZB IV, while the safety analysis included responders to 12 or 24 wk of RZB IV. The primary endpoint was clinical remission per Adapted Mayo score at wk 52. Key secondary endpoints included endoscopic improvement, HEMI, endoscopic remission, steroid-free clinical remission, maintenance of clinical remission, no bowel urgency, and no abdominal pain at wk 52. Results At baseline of induction, demographics and disease characteristics were similar between treatment groups; 75% of 548 patients had history of inadequate response or intolerance to ≥ 1 advanced therapy (AT). Patients receiving RZB180 (40.2%) and RZB360 (37.6%) achieved significantly higher rates of clinical remission vs WD (25.1%) (adjusted treatment difference vs WD: 16.3% and 14.2%, respectively; P ≤ .01) (Fig. 1A). Greater proportions of patients achieved endoscopic improvement, HEMI, endoscopic remission, steroid-free clinical remission, maintenance of clinical remission, no bowel urgency, and no abdominal pain with RZB180 and RZB360 vs WD (Fig. 1B). The overall rates of adverse events (AEs), and serious infections were similar among treatment groups (Table 1). Serious (presented as events/100 patient-years [E/100 PY]) (RZB180: 5.9; RZB360: 6.3; WD: 11.4) and severe AEs (RZB180: 1.6; RZB360: 4.0; WD: 8.0) were lower in the RZB arms vs WD. No active tuberculosis, adjudicated anaphylaxis, serious hypersensitivity, or adjudicated major adverse cardiovascular events were reported in any treatment group. Conclusion In patients with moderately to severely active UC responding to 12-week RZB induction therapy, RZB maintenance dosing with 180 mg and 360 mg SC was superior to placebo in achieving clinical remission as well as other key clinical, endoscopic, and histological-endoscopic endpoints. RZB was well-tolerated, with no new safety concerns observed.

Abstract During the 20th century, inflammatory bowel disease (IBD) was considered a disease of early-industrialized regions in North America, Europe, and Oceania. At the turn of the 21st century, incidence of IBD increased in newly-industrialized and emerging regions in Africa, Asia, and Latin America, while prevalence in early-industrialized regions started to grow steadily. Changes in incidence and prevalence denote evolution of IBD across four epidemiologic stages: Stage 1 (Emergence), characterized by low incidence and prevalence; stage 2 (Acceleration in Incidence), characterized by rapidly rising incidence and low prevalence; and stage 3 (Compounding Prevalence), characterized by decelerating, plateauing, or declining incidence and steadily rising prevalence. A fourth stage (Prevalence Equilibrium) has been proposed where the slope of prevalence plateaus due to shifting demographics of an aging IBD population, but it has not yet been evidenced. To date, these stages have been theoretical without specific incidence/prevalence indicators defining transition points. Using real-world data from 490 population-based studies comprising 80 global regions and spanning over a century (1920–2023), we show spatiotemporal transitions across stages 1–3 and model transition towards stage 4. Understanding the evolution of IBD across epidemiologic stages allows healthcare systems to better prepare for the future worldwide burden of IBD.

Delirium is common in hospitalised patients, and there is currently no specific treatment. Identifying and treating underlying somatic causes of delirium is the first priority once delirium is diagnosed. Several international guidelines provide clinicians with an evidence-based approach to screening, diagnosis and symptomatic treatment. However, current guidelines do not offer a structured approach to identification of underlying causes. A panel of 37 internationally recognised delirium experts from diverse medical backgrounds worked together in a modified Delphi approach via an online platform. Consensus was reached after five voting rounds. The final product of this project is a set of three delirium management algorithms (the Delirium Delphi Algorithms), one for ward patients, one for patients after cardiac surgery and one for patients in the intensive care unit.