Are There Sex-Related Differences in the Effectiveness of Janus Kinase Inhibitors in Rheumatoid Arthritis Patients?

Background: There is evidence suggesting the existence of sex differences in the effectiveness of specific drug classes for rheumatoid arthritis (RA). Our study stands as the first to elucidate sex-related differences in the effectiveness of Janus kinase (JAK) inhibitors. Methods: The study involved 150 RA patients treated with tofacitinib, baricitinib, upadacitinib, or filgotinib between September 2017 and October 2023. Sex differences in achieving remission and low disease activity (LDA) were identified through logistic regression analyses. Sex disparities in treatment effectiveness survival were evaluated through the Kaplan-Meier estimate, employing the log-rank test for comparison. The Cox model was applied to analyze the variable sex as a potential factor that could influence the maintenance of the JAK inhibitor treatment effectiveness. Results: Concerning the achievement of remission and LDA, no differences were observed between sexes in terms of the 28-joint Disease Activity Score (DAS28) C-reactive protein (CRP), the Clinical Disease Activity Index (CDAI), and the Simplified Disease Activity Index (SDAI). With respect to the DAS28-erythrocyte sedimentation rate (ESR), female patients, compared to males, possessed 70% lower odds of achieving remission (p = 0.018) and 66% lower odds of achieving LDA (p = 0.023). No differences were observed in treatment effectiveness survival between sexes (p = 0.703). Sex was not found to influence the survival of JAK inhibitor treatment effectiveness (p = 0.704). Conclusions: Being a female or male patient does not entail differences in the effectiveness of the JAK inhibitor treatment. Our findings encourage the consideration of a global pool of composite indices (DAS28-ESR/CRP, CDAI, SDAI) to measure RA disease activity, thus individualizing the target value as advocated by the treat-to-target strategy.

The Effect of the Drug-Related Problems Prevention Bundle on Early Readmissions in Patients From the Emergency Department: A Randomized Clinical Trial.

BACKGROUND: Drug-related problems (DRPs) are prevalent and avoidable disease that patients experience due to drug use or nonuse. However, secondary prevention policies have not yet been systematized. OBJECTIVE: To assess the clinical impact of a secondary prevention bundle for DRPs in patients who visited the emergency department (ED) for medicine-related problems. METHODS: A single-center randomized clinical trial was conducted from August 28, 2019, to January 28, 2021, with 1-month follow-up. We included 769 adult patients who visited ED with a DRP associated with cardiovascular, alimentary tract, and metabolic system medications. For the intervention group, a DRP prevention bundle, consisting of a combined strategy initiated in the ED was applied. Patients in the control group received standard pharmaceutical care. Intervention was evaluated in terms of 30-day hospital readmission due to any cause. RESULTS: Final analysis included 769 patients, of which 68 (8.8%) were readmitted within 30 days (control group, 40 of 386 [cumulative incidence: 10.4%]; intervention group, 28 of 383 [cumulative incidence, 7.3%]). After adjustment of the model for chronic heart failure, there was a lower incidence of hospital readmission among patients in the intervention group compared with those in the control group, odds ratio: 0.59 [95% confidence interval: 0.37-0.97]; number needed to treat (NNT) = 32. No significant differences in other outcomes were observed. CONCLUSION AND RELEVANCE: In this clinical trial, DRP prevention bundle in adjusted analysis decreased the rate of 30-day hospital readmission for any cause in patients who visited ED for a DRP. TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT03607097).

Risk factors for emergency department revisit in elderly patients with gastrointestinal bleeding secondary to anticoagulant therapy.

OBJECTIVE: To evaluate the frequency of emergency department (ED) revisits among elderly patients with gastrointestinal bleeding secondary to anticoagulant treatment and identify factors associated with an increased risk of ED revisits. METHODS: A 3-year retrospective observational study was designed, including elderly patients (≥65 years) with atrial fibrillation and undergoing oral anticoagulation therapy who visited the ED for gastrointestinal bleeding. To evaluate the risk factors for 30-day revisit, a multivariate analysis was designed including comorbidities, concomitant treatment, change in anticoagulant treatment and prescription of direct-acting oral anticoagulants. RESULTS: 80 patients were included. At discharge, anticoagulation therapy was modified in 21 (26.2%) patients; and changed from an oral anticoagulant to heparin in 17 (21.2%) patients and to another oral anticoagulant in 4 (5.0%) patients. Anticoagulant treatment was withdrawn in 5 (6.3%) patients at discharge. Eleven (13.7%) patients revisited the ED 30 days after hospital discharge for bleeding episodes. No differences in the frequency of revisit to the ED were observed in the patients who changed their anticoagulant treatment at discharge. In the multivariate analysis, chronic kidney disease was the only factor significantly associated with revisits at 30 days. CONCLUSIONS: Elderly patients who experience a first episode of gastrointestinal bleeding have a high risk of revisiting the ED for a bleeding episode, with no particular differences between the types of anticoagulant prescribed at discharge.

Impact of a pharmaceutical care programme for patients with chronic disease initiated at the emergency department on drug-related negative outcomes: a randomised controlled trial.

BACKGROUND: The resolution of potential drug-related problems is a priority of pharmaceutical care programmes. OBJECTIVES: To assess the clinical impact on drug-related negative outcomes of a pharmaceutical care programme focusing on the resolution of potential drug-related problems, initiated in the emergency department for patients with heart failure (HF) and/or chronic obstructive pulmonary disease (COPD). METHODS: Controlled trials, in which older adults (≥65 years) receiving four or more medications admitted to the emergency department for ≥12 hours for worsening of HF and/or COPD were randomised (1:1) to either a pharmaceutical care programme focusing on resolving potential drug-related problems initiated at the emergency department (intervention group (IG)) or standard care (control group). Comparisons between the groups were made for the proportion of patients with drug-related negative outcomes, number of drug-related negative outcomes per patient, mean stay, patients readmitted within 180 days and 180-day mortality. RESULTS: 118 patients were included, 59 in each group. Fewer patients in the IG had drug-related negative outcomes (37 (62.7%) vs 47 (79.7%) in the control group (p=0.042)). Fewer drug-related negative outcomes per patient occurred in the IG (56 (0.95 per patient) vs 85 (1.44 per patient) in the control group (p=0.01)). The mean stay was similar between groups (194.7 hours in the IG vs 242.5 hours in the control group (p=0.186)). No difference in revisits within 180 days was found (32 (54.24%) in the IG vs 22 (37.3%) in the control group (p=0.065)). 180-Day mortality was detected in 11 (18.6%) patients in the IG compared with 13 (22%) in the control group (p=0.647). CONCLUSION: A pharmaceutical care programme focusing on resolving potential drug-related problems initiated at the emergency department has a favourable clinical impact, as it reduces the number and prevalence of drug-related negative outcomes. No difference was found in other outcome variables.Trial registration number NCT02368548.

IL-6, IL-10 and TNFα do not improve early detection of post-endoscopic retrograde cholangiopancreatography acute pancreatitis: a prospective cohort study.

The most reliable indicators for post-ERCP acute pancreatitis are elevated amylase levels and abdominal pain 24 hours after ERCP. As ERCP is often performed on an outpatient basis, earlier diagnosis is important. We aimed to identify early predictors of post-ERCP pancreatitis. We prospectively analyzed IL-6, IL-10, TNFα, CRP, amylase and lipase before and 4 hours after ERCP, and studied their association with abdominal pain. We included 510 patients. Post-ERCP pancreatitis occurred in 36 patients (7.1%). IL-6, IL-10, TNFα and CRP were not associated with post-ERCP pancreatitis. Levels of amylase and lipase were higher in patients with pancreatitis (522 U/L and 1808 U/L vs. 78 U/L and 61 U/L, respectively; p < 0.001). A cut-off of 218 U/L for amylase (x2.2 ULN) and 355 U/L for lipase (x6 ULN) had a negative predictive value of 99.2% and 99.5%, respectively. Amylase and lipase present a good correlation (Pearson coefficient 0.912). Among 342 (67.1%) patients without abdominal pain at 4 hours, post-ERCP pancreatitis was diagnosed in 8 (2.3%). Only 4 of these patients presented amylase or lipase > 3 ULN. Amylase and lipase were the only markers of post-ERCP pancreatitis 4 hours after the procedure.

Somatostatin for prevention of post-ERCP pancreatitis: a randomized, double-blind trial.

BACKGROUND AND STUDY AIMS: Meta-analyses suggest that an intravenous bolus or a high dose continuous infusion of somatostatin reduces the incidence of acute pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). Clinical guidelines, however, do not recommend this prophylaxis. The aim of this randomized, double-blind clinical trial was to evaluate the effect of somatostatin on the incidence of post-ERCP pancreatitis. PATIENTS AND METHODS: Patients undergoing ERCP at a single center were randomized to either intravenous bolus of somatostatin followed by a short (4-hour) continuous infusion, or to a similar placebo regimen. The primary outcome was post-ERCP pancreatitis, defined as abdominal pain with an amylase level at least three times higher than the upper limit of normality 24 hours after the ERCP and requiring admission for at least 2 days. RESULTS: A total of 510 patients were enrolled (255 patients per group) and all completed follow-up. The main indications for ERCP were choledocholithiasis (62 %), and biliary malignant stricture (31 %). Post-ERCP pancreatitis occurred in 19 patients (7.5 %) in the somatostatin group and 17 patients (6.7 %) in the placebo group (relative risk [RR] 1.12, 95 % confidence interval [95 %CI] 0.59 - 2.1; P = 0.73). The number of cases of moderate or severe acute pancreatitis was similar in the somatostatin (2.4 %) and the placebo (3.5 %) groups (RR 0.67, 95 %CI 0.24 - 1.85, P = 0.43). No side effects were observed related to the use of somatostatin. CONCLUSIONS: Administration of an intravenous bolus of somatostatin followed by a short continuous infusion does not reduce the incidence of post-ERCP pancreatitis. Clinical Trials.gov number: NCT01060826.