Loftus, Edward V

AbstractBackgroundThis retrospective study gathered medical/pharmacy claims data on patients with inflammatory bowel disease (IBD) between January 01, 2000 and March 31, 2019 from the IBM MarketScan commercial claims database to assess the real-world impact of fatigue on healthcare costs in patients newly diagnosed with IBD.MethodsEligible participants were ≥18 years, newly diagnosed with IBD (≥2 separate claims), and had ≥12 months of continuous database enrollment before and after fatigue diagnosis. The date of fatigue diagnosis was the index date; participants were followed for 12 months post-index. Patients with (cases) or without (controls) fatigue were matched 1:1 by propensity score matching. Patients with evidence of prior IBD diagnosis/treatment, or those with a chronic disease other than IBD wherein fatigue is the primary symptom, were excluded. Healthcare resource utilization (HCRU), including hospitalizations, inpatient and outpatient visits, and associated costs were compared between cases and controls.ResultsMatched IBD cohorts (21 321 cases/21 321 controls) were identified (42% Crohn’s disease [CD] and 58% ulcerative colitis [UC]) with similar baseline characteristics (average age: 46 years; 60% female). Cases versus controls had significantly more all-cause outpatient visits (incidence rate ratio [IRR], 95% confidence intervals [95% CI]: 1.64 [1.61, 1.67], P < .001) and all-cause hospitalizations (IRR [95% CI]: 1.92 [1.81, 2.04], P < .001); as well as significantly higher all-cause total direct healthcare costs (mean: $24 620 vs. $15 324; P < .001). Similar findings were observed for IBD-related outcomes, as well as in CD- and UC-specific subgroups.ConclusionsPresence of fatigue is associated with an increase in HCRU and total medical costs among patients newly diagnosed with IBD.

Abstract Background We evaluated the health-related quality of life (HRQoL) benefits of upadacitinib (UPA) induction and maintenance treatment in a phase 3 study of patients with ulcerative colitis (UC) across a broad range of patient-centered outcomes. Methods Patients received UPA 45 mg once daily or placebo as induction treatment for 8 weeks. Patients who achieved clinical response were rerandomized to receive once daily UPA 15 mg, 30 mg, or placebo as maintenance treatment for 52 weeks. The percentages of patients reporting a clinically meaningful within-person change from baseline in the Ulcerative Colitis Symptoms Questionnaire, Inflammatory Bowel Disease Questionnaire, Work Productivity and Impairment Questionnaire, 36-Item Short Form Survey, and European Quality of Life-5 Dimension 5 Levels were evaluated at weeks 2 and 8 of induction and at weeks 0 and 52 of maintenance. Results Significant improvements from baseline in all HRQoL measures except the Work Productivity and Impairment Questionnaire–absenteeism were achieved with UPA (P < .001) vs placebo as early as week 2 of induction. These improvements were sustained at week 52 with significantly more patients treated with either 15 mg or 30 mg UPA vs placebo achieving meaningful within-person change in the Ulcerative Colitis Symptoms Questionnaire; Inflammatory Bowel Disease Questionnaire; overall work impairment, presenteeism, and activity impairment; both 36-Item Short Form Survey Physical and Mental Component Summaries; and European Quality of Life-5 Dimension 5 Levels (P < .001). Conclusions Induction treatment with UPA 45 mg significantly improved HRQoL measures. A significantly higher percentage of patients who responded to induction treatment with UPA maintained clinically meaningful improvements consistently across a wide range of HRQoL outcomes after 52 weeks of maintenance therapy with UPA (15 mg and 30 mg) compared with placebo. (ClinicalTrials.gov, Numbers: NCT02819635, NCT03653026).

Abstract Inflammatory bowel disease (IBD), which comprises Crohn's disease and ulcerative colitis, is an idiopathic inflammatory condition of the gastrointestinal tract. The incidence and prevalence of IBD are rapidly increasing worldwide, particularly in newly industrialized regions such as Asia. Although a large medical armamentarium is available for treating this chronic disease, IBD imposes a marked global disease burden. To understand the complex etiopathogenesis of this condition, it is important to consider the rapidly changing trends in its epidemiology in Asia. During the past few decades, the incidence and prevalence of IBD have significantly increased in both Asian countries and Asian immigrants in Western countries. In this review, we aimed to study and update the epidemiology of IBD in diverse Asian regions and among Asian immigrants in North America and Europe. Moreover, we highlighted that this population exhibits a unique disease phenotype, such as male predominance and high frequency of perianal fistula in Crohn's disease. Also, a different disease phenotype including more complicated disease such as perianal complications was noted in Asian Americans and Asian Europeans.

Abstract Background In patients with ulcerative colitis (UC), risks of infection and malignancies increase with age. Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of UC. This analysis assessed age as a risk factor for adverse events of special interest (AESI) in the tofacitinib UC clinical program. Methods Data were from phase 2 and 3 induction studies, a phase 3 maintenance study, and an open-label, long-term extension study. Efficacy and/or safety outcomes were analyzed in the Induction, Maintenance, and Overall Cohorts (patients who received ≥ 1 dose of tofacitinib), stratified by age. The effects of baseline demographic and disease-related factors on AESI incidence were assessed by Cox proportional-hazards regression analysis. Results In the Overall Cohort (1157 patients with ≤ 6.8 years’ tofacitinib treatment), age was a statistically significant predictor of herpes zoster (HZ), malignancies excluding nonmelanoma skin cancer (NMSC), and NMSC. Other statistically significant predictors included prior tumor necrosis factor inhibitor failure for HZ, NMSC, and opportunistic infection events, and prior duration of UC for malignancies excluding NMSC. In the Induction and Maintenance Cohorts, a higher proportion of tofacitinib-treated than placebo-treated patients (numerical difference) achieved the efficacy endpoints (endoscopic improvement, clinical remission, clinical response) across all age groups. Conclusions Older individuals receiving tofacitinib as induction and maintenance therapy to treat UC may have an increased risk of HZ, malignancies (excluding NMSC), and NMSC versus similarly treated younger patients, consistent with findings from the general population. Across all age groups, tofacitinib demonstrated greater efficacy than placebo as an induction and maintenance therapy. ClinicalTrials.gov Registration Numbers NCT00787202; NCT01465763; NCT01458951; NCT01458574; NCT01470612.

Abstract Background Upadacitinib is a selective Janus kinase inhibitor approved for the management of ulcerative colitis and is under evaluation for the management of Crohn’s disease [CD] in Phase 3 clinical trials. Aims Our goal was to describe our real-world experience with upadacitinib in CD. Methods This is a two-centre retrospective cohort study of adult patients with moderate to severe CD on upadacitinib. The primary outcome was clinical response and remission as determined by stool frequency and abdominal pain scores. Secondary endpoints included endoscopic response and remission as determined by change in Simple Endoscopic Score for CD. Outcomes were assessed at 3 months after starting upadacitinib and at the patient’s most recent follow-up. We further evaluated adverse events and dose-related response. Results A total of 45 CD patients received upadacitinib and were included in the safety analysis. Thirty-six patients received upadacitinib for CD, whereas nine received it for inflammatory arthritis [n = 8] or pyoderma [n = 1]. Thirty-three patients received upadacitinib for 3 months or longer and were included in the efficacy analysis. At the 3-month follow-up, 21 patients achieved clinical response [63.6%] and nine achieved clinical remission [27.2%]. At time of last follow-up, 23 patients had clinical response [69.7%], ten achieved clinical remission [30.3%] and four [28.6%] achieved endoscopic remission. Adverse events occurred in 12 patients [26.7%]. Two patients had a serious adverse event [4.5%] without associated mortality. Conclusion In this real-world cohort of highly refractory CD patients, upadacitinib was effective in inducing remission and had an acceptable safety profile.

SummaryBackgroundCrohn's disease has a substantial negative impact on health‐related quality of life (HRQoL).AimTo examine the effects of risankizumab on HRQoL in Crohn's diseaseMethodsWe analysed data from patients with Crohn's disease from 12‐week induction trials ADVANCE (N = 850) and MOTIVATE (N = 569) with risankizumab 600 mg or 1200 mg intravenous (IV) versus placebo IV and a 52‐week maintenance trial FORTIFY (N = 462) with risankizumab 180 or 360 mg subcutaneous (SC) versus placebo SC. Outcomes included Inflammatory Bowel Disease Questionnaire (IBDQ), Functional Assessment of Chronic Illness Therapy‐Fatigue (FACIT‐F), 36‐item Short Form Health Survey (SF‐36), EuroQol 5‐Dimension‐5‐Level (EQ‐5D‐5L) and work productivity. The mean change and percentages of patients achieving clinically meaningful improvement in all outcomes were determined at weeks 12 and 52.ResultsAt week 12, more patients in the risankizumab 600 or 1200 mg groups achieved IBDQ response than with placebo (ADVANCE: 70.2%, 75.5% vs. 47.8%, p ≤ 0.001; MOTIVATE: 61.7%, 68.5% vs. 48.2%, p ≤ 0.01) and FACIT‐F response (ADVANCE: 51.3%, 48.0% vs. 35.7%, p ≤ 0.01; MOTIVATE: 44.2%, 49.1% vs. 33.7%, p < 0.05). These improvements persisted at week 52 with risankizumab maintenance treatment. Similar trends were observed for SF‐36 physical and mental component summary scores, EQ‐5D‐5L and activity impairment within work productivity measures.ConclusionsRisankizumab induction therapy (600 or 1200 mg IV) led to clinically meaningful improvements in disease‐specific and general patient‐reported outcomes, including fatigue, in patients with moderate to severe Crohn's disease. These improvements were sustained after 52 weeks of risankizumab (180 or 360 mg SC) maintenance therapy.

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.

AbstractBackgroundAvascular necrosis (AVN) is a known adverse event associated with corticosteroid (CS) usage. Inflammatory bowel disease (IBD) is often treated with a CS for induction of remission. We sought to describe clinical features and outcomes of IBD patients with AVN.MethodsIn this retrospective, single-center, case-control study, patients with IBD who had a diagnosis of osteonecrosis, aseptic necrosis, or AVN from 1976 to 2009 were included, and each was matched with up to 2 controls (IBD but no AVN) on age, sex, IBD subtype, geographic area of residence, and date of IBD diagnosis. We abstracted risk factor data from the medical records. Conditional logistic regression was performed accounting for minor differences in age and date of first IBD visit to assess the relationship between putative risk factors and AVN, expressed as odds ratio and 95% confidence interval.ResultsEighty-five patients were diagnosed with IBD-AVN and were matched with 163 controls. The mean age at AVN diagnosis was 47.5 years. AVN was diagnosed a median of 12.2 years after IBD diagnosis, and the control group was followed for a median of 15 years after IBD diagnosis to ensure that they did not have AVN. Ten percent of patients with AVN did not have any CS exposure. History of arthropathy or estrogen use in Crohn’s disease and use of CS, osteoporosis, and history of arthropathy in ulcerative colitis were significantly associated with AVN.ConclusionsMost patients with IBD-AVN had multifocal involvement. Most had received CS, but many patients had other risk factors including arthropathy.

INTRODUCTION: Patients with ulcerative colitis (UC) regard rapid onset of action among the most important aspects of their treatment. We used the partial Mayo Clinic Score (pMCS) and component patient-reported subscores to assess the rapidity and sustainability of response to filgotinib, a once-daily, oral Janus kinase 1 preferential inhibitor, in adults with moderately to severely active UC in the phase 2b/3 SELECTION trial. The association between early symptomatic improvements and health-related quality of life (HRQoL) outcomes was also assessed. METHODS: In these post hoc analyses of the double-blinded, randomized, placebo-controlled 58-week SELECTION trial (NCT02914522), rectal bleeding and stool frequency diary data on days 1–15 and pMCS remission and response at multiple time points including weeks 10 and 58 were evaluated. HRQoL was assessed using the Inflammatory Bowel Disease Questionnaire at weeks 10 and 58. RESULTS: Filgotinib 200 mg relative to placebo improved rectal bleeding and stool frequency within 7 days ( P < 0.05). By week 2, greater proportions of filgotinib 200 mg-treated patients than placebo-treated patients achieved pMCS remission (biologic-naive, 15.1% vs 8.0%, P = 0.0410; biologic-experienced, 10.3% vs 4.2%, P = 0.0274). A similar treatment effect was observed at week 58 ( P < 0.0001). Day 7 rectal bleeding and stool frequency subscores were associated with the Mayo Clinic Score response at weeks 10 and 58. Patients in pMCS remission at weeks 10 and 58 had greater improvements in the Inflammatory Bowel Disease Questionnaire score than those not in pMCS remission. DISCUSSION: Filgotinib 200 mg daily resulted in rapid and sustained improvements in both UC symptoms and HRQoL.