Switching within out of class following first-line TNFi failure in ulcerative colitis: real-world outcomes from a German claims data analysis

Background: Biologic agents have demonstrated efficacy in treating ulcerative colitis (UC); however, treatment failure to tumor necrosis factor inhibitors (TNFi) is common in the real world. Data on preferential sequencing in clinical practice after failure remain limited. Objectives: This study aimed to evaluate real-world outcomes of patients cycling to TNFis or switching to non-TNFi biologics following first-line failure with TNFis. Design: Retrospective cohort study in Germany. Methods: Adult patients with UC were identified using administrative claims data from 1 May 2014 to 30 June 2022 provided by a statutory sickness fund. Patients newly initiating first-line therapy with TNFis and then switching to another agent were identified. Patients were defined as within-class switched (WCS), if they cycled to another TNFi, or outside-class switchers (OCS), if they switched to a non-TNFi biologic [ustekinumab (UST) or vedolizumab (VDZ)] and followed from index (switch date) to death, insurance end, or study end on 30 June 2022. Inverse probability of treatment weighting (IPTW) was performed to adjust for differences in baseline characteristics between groups, and weighted Cox regression models were used to compare primary (time to discontinuation and second treatment switch) and secondary outcomes (corticosteroid-free drug survival). Results: We identified 166 patients initiating TNFis and switching to a subsequent treatment (mean age: 42.9 years, 49.4% female). Following IPTW, there were 71 and 76 patients in the WCS and OCS groups, respectively. Compared to OCS, WCS were more likely to discontinue the new therapy [hazard ratio (HR), 1.82, 95% confidence interval (CI), 1.14–2.89, p  = 0.012], and switch a second time (HR, 3.46, 95% CI, 1.89–6.36, p  < 0.001). Moreover, WCS showed an increased likelihood of initiating prolonged corticosteroid therapy (HR, 1.42, 95% CI, 0.77–2.59, p  = 0.260); however, the results were not significant. Conclusion: Following first-line TNFi failure, this study suggests that real-world outcomes among patients with UC are less favorable when cycling to another TNFi, compared to switching to a non-TNFi such as UST or VDZ

Nurr1:RXRα heterodimer activation as monotherapy for Parkinson’s disease

Significance In Parkinson’s disease (PD), dopamine (DA)-producing neurons gradually degenerate, leading to DA deficiency and to the main symptoms of PD. Current medications do not impede neurodegeneration, but relieve symptoms by replenishing DA; however, their chronic use causes serious side effects. We targeted a protein required for the development and function of DA neurons by designing a chemical compound that, by activating this protein, increases DA and improves symptoms without current treatment side effects while simultaneously preventing neuron loss in PD mice. Our findings point to a monotherapy that can both impede PD progression and concurrently improve symptoms of PD.</jats:p