Abstract
Background
Treatment with a combination of biologic drugs or advanced molecules represents a seldom-used therapeutic option for inflammatory bowel disease (IBD). Data on the effectiveness of ...these combinations of treatment are limited.
The objective of this study is to assess the effectiveness of combination therapy in IBD patients.
Methods
A retrospective, single-center observational study was conducted. Patients with IBD treated with a combination of biologic drugs or advanced molecules from January 2020 to September 2023 were analyzed.
Clinical, demographic, and therapeutic variables were collected. The clinical response rate was evaluated using the Harvey-Bradshaw Index for Crohn's disease (CD) and the partial Mayo score for ulcerative colitis (UC) at the initiation and 6 months into treatment.
Bivariate analysis was performed to identify variables associated with clinical response.
Long-term treatment survival was studied using Kaplan-Meier curve.
Results
A total of 9 patients were included: 7 (77.8%) with CD and 2 (22.2%) with UC. The majority (66.6%) had received more than two biologic treatments. Patient characteristics are described in Table 1. Combination treatment was initiated due to partial response to monotherapy in 2 patients (22.2%) and monotherapy failure in 7 (77.8%). The most commonly used combination was ustekinumab-vedolizumab (n=6, 66.6%). Three patients (33.3%) had a clinical response at 6 months, with one patient achieving clinical remission.
In the bivariate analysis, partial response to monotherapy as an indication for a second biologic and elevated PCR at the start of treatment were associated with a higher clinical response (p=0.03 and p=0.04, respectively).
The median survival of the combination treatment was 309 days (±109) (Fig. 1). At the end of the follow-up, 2 patients (22.2%) continued with combination treatment (average of 251 days). In 4 cases the treatment was switched to a JAK inhibitor, one patient required surgery and, finally, two patients needed surgery and treatment change.
Conclusion
The combination treatment have a low long term effectiveness in patients refractory to conventional treatment, although it may be a valid option for that subgroup of patients showing a partial response to monotherapy.
Abstract
Background
Background: Inflammatory Bowel Disease (IBD) has an important economic impact in healthcare costs and resources utilization. Population data on this topic are scarce. The aim of ...this study was to evaluate the current healthcare expenditures of IBD in a population-wide study Catalonia.
Methods
Methods: All patients with IBD included in the Catalan Health Surveillance System (CHSS) were included. CHSS includes data on more than 7 million individuals in 2020, 34,823 of them being diagnosed of IBD.
Data on prevalence, incidence, comorbidities, stratification of risk, use of healthcare resources and economic impact were extracted from the CHSS according to ICD-10-CM codes. Health expenditure was calculated according to the standard costs of each service provided by the Department of Health (Generalitat de Catalunya). The utilization of healthcare services and associated expenditure of IBD were compared with a control group of patients not identified as IBD adjusted by age, sex, and income level (hereinafter referred to as “non-IBD”). IBD costs were separately provided for Crohn’s Disease (CD) and Ulcerative Colitis (UC).
Results
Results: The prevalence and incidence of IBD in 2020 was 405.6 and 27.2 per 100,000 inhabitants, respectively. Total number of IBD patients in 2020 was 37,381. Prevalence of comorbidities (neoplasia, arthritis, chronic obstructive pulmonary disease, asthma, cardiac disease, ictus and mental disease) was higher in IBD patients’ when compared to non-IBD population. The risk of hospitalization in IBD was twice those of the non-IBD individuals.
The global healthcare expenditures of patient with IBD was 164M€. The average annual expenditure for an IBD patient was 4M€ versus 1M€ for non-IBD population; being more than 3.4-fold higher. Cost in UC was 3,360€ and 5,699€ for CD patient.
Conclusion
Conclusion: Patients with IBD presented a higher risk of comorbidities (1.5-2 fold) and healthcare resources utilization. Healthcare expenditure per patient were approximately 3.4 times higher than the non-IBD population.
Abstract
Background
Ustekinumab (UST) is a monoclonal antibody that inhibits the p40 subunit of IL-12 and IL-23, approved for the treatment of Crohn's Disease (CD) and Ulcerative Colitis (UC). Its ...administration is intravenous during induction and subcutaneous during maintenance. Several studies have assessed the efficacy of reinduction and intensification of this treatment in patients with loss of response. However, there are few studies evaluating the effectiveness of intravenous UST for maintenance.
The aim of the study is to evaluate the efficacy and safety of maintenance with intravenous UST in patients with Inflammatory Bowel Disease (IBD).
Methods
Observational, retrospective, and single-center study. All patients receiving maintenance with intravenous UST until June 2023 were reviewed. Clinical response was evaluated with Harvey-Bradshow Index for CD and partial Mayo for UC. Biochemical response was evaluated with calprotectin and C-reactive protein.
Results
A total of 29 patients with IBD (24 CD and 5 UC) were included. The mean follow-up of patients was 449 days (74-948). The cohort's characteristics are summarized in Table 1.
In all cases, intravenous maintenance was performed with UST 130mg/4 weeks. In 4 cases (13.8%), maintenance was initiated directly with intravenous UST. In 9 (31%) patients due to primary failure to UST and in 16 (55.2%) patients due to secondary failure.
The clinical response to intravenous UST maintenance in patients with CD at week 8 and 16 and at one year of follow-up was 87.5% (n=21/24), 83.3% (n=20/24), 73.3% (n=11/15) respectively. For UC, the response was 60% (n=3/5) at week 8 and 16 and at one year. The drug survival was 723 days (± 74) (Figure 1). No predictive variable for treatment response was identified. Two patients (both with CD) experienced recurrent respiratory infections as an adverse effect, without the need to discontinue UST.
Conclusion
Maintenance treatment with intravenous UST can be useful and safe in patients with severe IBD and/or failure of subcutaneous UST maintenance.
HIV-negative immunosuppressed patients comprise a heterogeneous group including transplant patients, patients undergoing treatment with immunosuppressors, uremic patients, alcoholics, undernourished ...patients, diabetics, patients on dialysis, elderly patients, and those diagnosed with severe or neoplastic processes. Epileptic seizures, focal neurologic signs, and meningoencephalitis are neurologic syndromes that require urgent action. In most of these situations, neuroimaging tests are necessary, but the findings can be different from those observed in immunocompetent patients in function of the inflammatory response. Infectious disease is the first diagnostic suspicion, and the identification of an opportunistic pathogen should be oriented in function of the type and degree of immunosuppression. Other neurologic emergencies include ischemic stroke, cerebral hemorrhage, neoplastic processes, and pharmacological neurotoxicity. This article reviews the role of neuroimaging in HIV-negative immunodepressed patients with a neurologic complication that requires urgent management.
Abstract
Background
Oral corticosteroids remain the treatment of choice for moderately active flares of ulcerative colitis (UC). In early controlled studies, oral corticosteroids achieved clinical ...remission rates of, 30–60% at, 30 days. Some small prospective studies observed that the administration of high-dose intravenous bolus of methyl-prednisolone accelerated their therapeutic action and increased the rate of clinical response. We aimed to evaluate if the outpatient administration of intravenous, high-dose, methyl-prednisolone bolus increases the efficacy of a conventional course of oral prednisone in moderately active UC.
Methods
Prospective, multicentre, controlled, randomized, open-label study comparing the therapeutic efficacy of a standard oral prednisone schedule with the same schedule preceded by a three-day regimen of high-dose intravenous bolus of methyl-prednisolone. Inclusion criteria were: Moderately active, left-sided/extensive UC (total Mayo score, 6–10), with no prior exposure to immunosuppressants or biologics, and no corticosteroid treatment in the last, 6 months. Patients were randomized to oral prednisone, 60mg/day (ORAL group) or the same schedule preceded by intravenous bolus of, 500mg of methyl-prednisolone for three consecutive days (BOLUS group), stratified by the baseline use of oral, 5ASA and UC onset. Early clinical response was defined as the reduction of the baseline partial Mayo Score (pMS) by at least three points with at least a decrease by, 1 point in rectal bleeding and with an absolute value of, 0 or, 1, seven days after starting treatment (EUDRA CT:, 2016-001170-15)(Clinicaltrials.gov: NCT02921555)
Results
In all, 71 patients (38 ORAL, 33 BOLUS) were included. At baseline, the median pMS was, 6 (IQR, 5–7). In, 21% of the patients, the index flare was the onset of UC and, 68% had never received systemic corticosteroids for UC. There were no differences in baseline clinical and demographic features between the two study groups. At day, 7, the proportion of patients fulfilling early clinical response criteria was similar in both groups (BOLUS, 63% vs. ORAL, 58%; p = 0.6), but a significantly greater reduction in pMS at day, 3 (-3.4. vs -1.7; p <0.0001) and a significantly higher proportion of patients in clinical remission (pMS <2) at day, 7 (57% vs, 29%; p = 0.017) were observed in the BOLUS group.
Conclusion
The addition of three high-dose intravenous bolus of methyl-prednisolone to a standard schedule of oral corticosteroids achieves a faster and more intense response in the short-term in moderately active flares of UC, but it does not increase the clinical response rate at seven days. The impact of these effects on the medium-term outcomes is still to be assessed.
Electrification systems based on the use of renewable energy sources are a suitable option for providing electricity to isolated communities autonomously. Wind and hybrid windaphotovoltaic (PV) ...systems are increasingly getting attention. To electrify scattered communities, designs that combine individual systems and microgrids have recently proven advantageous. In this paper we present a mathematical programming model to optimize the design of hybrid windaPV systems that solves the location of the windaPV generators and the design of the microgrids, taking into account the demand of the consumption points and the energy potential. The criterion is the minimization of the initial investment cost required to meet the demand. The proposed hybrid model is tested with realistic size instances and results show the instances are efficiently solved. Moreover, the model is applied to real case studies in Peru; obtained results verify that the hybrid model efficiently finds solutions that significantly reduce costs.
The popular Nelder and Mead (NM) algorithm has four parameters associated to the operations known as reflection, expansion, contraction and shrinkage. The authors set their values to 1, 2, 0.5 and ...0.5, respectively, which have been universally used. Here, we propose to use NM to calibrate itself. A computational experiment is carried out and results show that the parameter values originally proposed by NM are better than those obtained with more sophisticated ways.
Abstract
Background
Upadacitinib (UPA) has demonstrated its efficacy in patients with inflammatory bowel disease (IBD) in clinical trials. However, these results may differ from those achieved in ...clinical practice. Thus, persistence and safety should be analysed in a real-world scenario. Main aim: to evaluate the persistence of UPA in real life, both in Crohn’s disease (CD) and ulcerative colitis (UC). Secondary aims: to assess the effectiveness and safety of UPA.
Methods
Multicentre, retrospective study of IBD patients who received UPA for IBD in clinical practice. Persistence was calculated from the date of the first dose to the date of the last dose of UPA. For effectiveness assessment, only patients with active IBD at baseline were considered. Active disease was defined as Harvey-Bradshaw index >4 in CD, and partial Mayo score >2 in UC. Negative imputation method was used to deal with missing data. Cox regression and logistic regression analyses were used to identify predictive factors of treatment persistence and effectiveness, respectively.
Results
One hundred patients from 34 centres were included, 68 with CD and 32 with UC. All patients had been previously exposed to biologics (median 4, IQR 3-4), and 26% to JAK inhibitors (78% in UC); 37% of them were on steroids at baseline. Regarding UPA survival, 81% of patients remained on UPA at month 6, and 66% at month 12 (figure 1). Loss of response was observed in 34% per patient-year of follow-up. Dose intensification was required in 18%, 72% of whom responded clinically. Finally, 23 patients interrupted UPA during the follow-up. Age below 40 at UPA start and CD were associated with higher risk of UPA withdrawal (HR 2.4; 95%CI:1.0-5.7 and HR 3.7; 95%CI:1.0-12.9, respectively). Seventy-eight patients had active disease at baseline and were considered for the effectiveness analysis. Short-term clinical remission was achieved in 51%, 59% and 64% at week 4, 8 and 12; focusing on the type of IBD, clinical remission was achieved in 79% of UC vs. 54% of CD (p=0.03) at week 12. In the long-term, 53% and 42% remained in clinical remission at months 6 and 12. Clinical remission in patients exposed to JAK inhibitors was achieved in 75% and 79% at week 8 and 12, respectively; and in the long-term, in 54% and 55% at months 6 and 12. A total of 41 patients (41%) presented at least one adverse event (Table 1).
Conclusion
In the largest real-life cohort of IBD patients treated with UPA, the proportion of patients maintaining UPA at 12 months seems relatively high, regardless of prior exposure to JAK inhibitors. UPA seems to be effective in inducing and maintaining clinical remission, both in CD and in UC. The safety profile was similar to that previously described.
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