Hopitaux Civils de Colmar

Abstract Background Ulcerative colitis (UC) requires effective therapeutic strategies to induce and maintain remission. Upadacitinib, a selective JAK1 inhibitor, has shown strong efficacy in clinical trials; however, real-world evidence in Latin American populations remains scarce. The UPARECOL-UC study evaluated the effectiveness and safety of upadacitinib in Colombian patients with UC during induction (8–16 weeks) and maintenance (24 weeks) under routine clinical practice. Methods A prospective multicentre cohort study was conducted across Colombian reference centres including adults with confirmed UC (clinical, endoscopic, and histological criteria) who initiated upadacitinib between 2024 and 2025 for ≥8 weeks. Effectiveness outcomes included clinical response, clinical remission, and steroid-free remission. Objective biomarkers (C-reactive protein, faecal calprotectin, haemoglobin) were monitored at baseline and follow-up. Safety variables included adverse events (AEs), serious AEs, infections, and treatment discontinuation. Results A total of 47 patients were included in the induction analysis. After 8–16 weeks, clinical remission was achieved in 61.7% (29/47), with steroid-free remission in 71.4% of responders. At week 24, clinical remission increased to 90% (18/20), and steroid-free remission reached 88.2%. Endoscopic remission (Mayo 0–1) was 85% among patients reassessed endoscopically during maintenance. Significant reductions in inflammatory biomarkers were observed during follow-up, supporting clinical improvement. Colectomy occurred in 5.4% of patients during induction, with no colectomies during maintenance. Overall, 30.2% experienced any AE; acne was the most common (25.6%). Serious infections occurred in 4.7% . Treatment discontinuation due to AEs occurred in 9.3% of the cohort. No new safety signals were identified. Conclusion Upadacitinib demonstrated high real-world effectiveness for both induction and maintenance in this Colombian UC cohort, composed largely of patients with severe and treatment-refractory disease. Improvements in clinical outcomes were accompanied by significant reductions in inflammatory biomarkers. The safety profile was consistent with previous clinical and real-world data, supporting upadacitinib as an effective therapeutic option for UC in routine practice. Conflict of interest: Parra Izquierdo, Leidy Viviana: No conflict of interest Gil Parada, Fabio Leonel: No conflict of interest Juliao Baños, Fabián: No conflict of interest Puentes-Manosalva, Fabian Eduardo: No conflict of interest Cuervo-Pico, Pedro-Eduardo: No conflict of interest Galiano, Maria Teresa: No conflict of interest Riveros, Javier: No conflict of interest Gomez Venegas, Alvaro: No conflict of interest Medrano-Almanza, Carlos Andres: No conflict of interest Perea, Daniel: No conflict of interest Ballesteros, Manuel: No conflict of interest Barreto Perez, Jonathan: No conflict of interest Cuadros-Mendoza, Carlos Augusto: No conflict of interest Guzman, Gerardo: No conflict of interest Gutierrez Raba, Aura: No conflict of interest Soto Mora, Jahir: No conflict of interest Dr. Frías-Ordoñez, Juan: No conflict of interest

Abstract Background Defaecatory urgency is a cardinal and distressing symptom in ulcerative colitis (UC), strongly associated with disease activity and reduced quality of life. Its resolution represents a key therapeutic goal, often paralleling mucosal healing and remission. Upadacitinib (UPA), a selective JAK1 inhibitor, has demonstrated robust efficacy for induction and maintenance of remission in UC; however, its specific impact on urgency in real-world Latin American settings remains poorly characterised. Methods We conducted a multicentre observational study including adults with moderate-to-severe UC treated with UPA 45 mg/day for induction and 30 mg/day for maintenance. Changes in defaecatory urgency (present/absent), clinical response (≥3-point decrease in Mayo score), and clinical remission (Mayo < 2) were evaluated at weeks 8–16 (induction) and 24 (maintenance). Biochemical remission was defined as faecal calprotectin < 150 µg/g and/or C-reactive protein < 5 mg/L. Absolute differences were calculated with 95 % confidence intervals (CI), and Fisher’s exact test was applied for categorical variables (p < 0.05). Results A total of 47 patients with UC were included; mean age 39.8 ± 14.6 years; 59.6 % female; 83 % previously exposed to at least one anti-TNF agent. At baseline, 66 % of patients reported defaecatory urgency, which decreased to 31.9 % after induction (Δ − 34.1 %; 95 % CI − 49.5 to − 18.7; p = 0.001) and 25.5 % at six months (p = 0.003). Clinical response was achieved in 81.2 % (95 % CI 66.1–91.4), and clinical remission in 61.7 % (95 % CI 46.4–75.1). Improvement in urgency strongly correlated with clinical remission (r = 0.72; p < 0.001). Biochemical remission (faecal calprotectin < 150 µg/g or CRP < 5 mg/L) occurred in 57.4 % of patients. No serious adverse events were observed; mild transaminase elevations occurred in 8.5 %. Conclusion Upadacitinib rapidly and sustainably reduced defaecatory urgency in Colombian patients with moderate-to-severe UC, with improvement in over two-thirds of cases and a strong association with clinical remission and biomarker normalisation. These findings provide the first real-world Latin American evidence highlighting upadacitinib’s impact on patient-centred symptomatic control in ulcerative colitis, supporting its role as an effective induction and maintenance therapy.

TTick-borne encephalitis (TBE), caused by the tick-borne encephalitis virus (TBEV), is primarily transmitted to humans through Ixodes tick bites. TBEV comprises three main subtypes describing distinct severity and clinical course: European (TBEV-Eu), Siberian (TBEV-Sib), and Far Eastern (TBEV-Fe). Over the past decade, TBE epidemiology significantly changed in Europe, with an increasing incidence in endemic countries and the discovery of new human case foci and areas of virus circulation. This emergence involves many factors whose impact is not easily determined. While most TBEV-Eu infections are asymptomatic, some patients develop meningitis, or meningoencephalitis, associated with post-infectious sequelae. Several studies recently evaluated the burdens of these sequelae and their associated medical costs. During the complex TBE neuropathogenesis, the antagonism between viral and immunological factors is not clearly identified, nor are the predictive factors of clinical severity. New diagnostic tools are being developed. While TBE treatment is currently only symptomatic, several antiviral treatments are under study.

The objective of this systematic review was to assess adverse effects and long-term withdrawal symptoms of prolonged glucocorticoid (GC) therapy in patients with rheumatic diseases, e.g., rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The review synthesizes evidence from randomized controlled trials (RCTs), clinical trials, and observational cohorts in order to evaluate the safety and tolerability of long-term GC use and the effect of GC withdrawal strategies. The systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. A complete literature search on PubMed, Scopus, and Google Scholar was performed using both text words and controlled vocabulary. Only RCTs and clinical trials published in English from January 1, 2020, to October 31, 2025, were included. Only RCTs and observational cohort studies were considered. RCT's methodological quality was assessed using the Cochrane Risk of Bias 2.0 (RoB 2.0) tool and non-randomized studies by the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool. ROBVIS software (University of Bristol, Bristol, United Kingdom) was used to visualize the RoB. A total of 10 studies of low to moderate RoBs were considered to synthesize evidence. In conclusion, the balance of evidence strongly supports the European Alliance of Associations for Rheumatology (EULAR) recommendations to taper and discontinue GCs whenever clinically feasible. Although there is actual danger of disease flare, the evidence suggests less long-term organ damage, particularly in SLE, and prevention of multi-system adverse events, indicating a clear clinical advantage for attempting GC withdrawal. This reinforces the significance of discontinuation as a cornerstone of standard care. The findings support a gradual process of tapering as a safer and more efficient solution than sudden withdrawal. Thus, clinicians need to take into account the individual patient factors to increase the likelihood of successful discontinuation.

Abstract BACKGROUND WHO Grade 3 IDH-mutant diffuse gliomas (oligodendrogliomas (O3) or astrocytomas (A3)) are chemosensitive tumors. A POLA Network study recently showed a significant improvement in overall survival (OS) in patients with O3 treated by PCV (Procarbazine (PCZ), CCNU, Vincristine (VCR)) regimen in addition to radiotherapy (RT) versus Temozolomide and RT protocol. The same tendency was reported in A3 patients. However, the safety profile of PCV regimen is considered to be less favorable, leading to dose adaptation and early treatment discontinuation. The aim of our study was to describe the toxicity related to PCV regimen and the potential impact of an early PCZ or VCR discontinuation on progression-free survival (PFS) in patients with newly diagnosed O3 or A3. MATERIAL AND METHODS We analyzed the prospectively collected clinical, histo-molecular, survival and treatment data of patients with newly diagnosed A3 or O3 treated in first line by PCV and RT in 3 French POLA centers. All analyses were performed using RStudio (including “Maxstat” package). RESULTS A total of 191 patients were included (O3: 45.7% and A3: 54.3%) and 183 were analyzed for PFS after exclusion of early progression under treatment. Median follow-up was 65 months (range 14-145). Median PFS and median OS were not reached. 36.7% of patients received RT before PCV and median duration of PCV was 7 months (range 1-13). Grade 3/4 toxicities were reported in 78 patients (43%). The most common were cytopenia, occurring in 55 patients (30%), and liver cytolysis in 15 patients (8.2%). Dose reductions were required for PCZ and VCR in 10.9% and 52.5% of patients, respectively. Permanent treatment discontinuation occurred in 81 patients (44.2%) for PCZ and 97 patients (51.2%) for VCR. Neither the occurrence of grade 3/4 toxicity, nor PCV cycle delay (6 vs 8 weeks) impacted patient PFS. VCR dose decrease or premature discontinuation did not impact patient PFS. In contrast, a negative impact was observed in patients receiving less than 4 cycles of PCZ (p=0.037) or a total cumulative dose less than 4410 mg/m2 (p=0.049). CONCLUSION In newly patients diagnosed with a grade 3 IDH-mutant gliomas treated by RT and PCV, PCV toxicity, cycle delay or premature discontinuation of VCR did not impact patient PFS. However, PCZ discontinuation or reduced cumulative dose is associated to shorter PFS, highlighting the need for optimal PCZ toxicity management, including dose adaptation, cycle delay for toxicity recovery and improvement in symptom management.