Gisbert, Javier P

Abstract Background and Aims Upadacitinib (UPA)—an oral, reversible selective Janus kinase inhibitor—has a favorable benefit–risk profile for patients with Crohn’s disease (CD) and ulcerative colitis (UC). We evaluated the benefit–risk of UPA in select subgroups with CD or UC. Methods Patients were randomized to UPA 45 mg (UPA45) once daily (QD) or placebo (PBO) induction for 12 (CD: U-EXCEED, U-EXCEL) or 8 weeks (UC: U-ACHIEVE, U-ACCOMPLISH). Clinical responders were re-randomized to QD UPA 15 mg (UPA15), UPA 30 mg (UPA30), or PBO for 52-week maintenance (CD: U-ENDURE; UC: U-ACHIEVE). This exploratory post hoc analysis assessed efficacy and safety outcomes (adverse events of special interest [AESIs]: serious infections, major adverse cardiovascular [CV] events, malignancies, and venous thromboembolic events) by CV risk, prior treatment failure, and age. Results This analysis included 1021 patients with CD and 1097 with UC during induction, and 673 with CD and 746 with UC during maintenance. Improved efficacy outcomes comparable to the overall study populations were observed with UPA versus PBO across subgroups. Patients receiving UPA30 generally showed numerically higher rates of improvements versus UPA15. AESI rates were generally comparable between UPA and PBO across subgroups except for numerically higher rates of herpes zoster and serious infections in CD with UPA. Conclusions UPA resulted in consistent benefit versus placebo across CV risk, prior treatment failure, and age subgroups. No treatment differences were seen in AESIs across subgroups except herpes zoster and serious infections, reinforcing the favorable benefit–risk profile for UPA in CD and UC seen in the overall study populations. Clinical trial numbers NCT02819635, NCT03653026, NCT03345836, NCT03345849, NCT03345823

SummaryBackgroundRecent advances in eosinophilic oesophagitis (EoE) have confirmed the existence of a new disease phenotype, proton pump inhibitor (PPI)‐responsive oesophageal eosinophilia (PPI‐REE).AimTo summarise evidence supporting the use of PPI therapy in patients with suspected EoE (oesophageal dysfunction plus >15 eos/HPF in oesophageal biopsies).MethodsA literature search was conducted through MEDLINE, using the MeSH search terms ‘eosinophilic oesophagitis’, ‘proton pump inhibitors’ and ‘oesophageal eosinophilia’. Relevant articles and their reference lists were identified through manual review.ResultsTen articles, including 258 patients with suspected EoE (152 children, 106 adults) undergoing clinico‐histological re‐evaluation after PPI therapy, were identified. In children, clinical response ranged from 78% to 86% and histological remission from 23% to 40%. In adults, symptom response ranged from 25% to 80% and histological remission from 33% to 61%. Among PPI‐REE patients with oesophageal pH‐monitoring, 35 showed pathological and 10 normal studies. PPI‐REE was significantly commoner with documented gastro‐oesophageal reflux disease (GERD) when compared to patients with negative pH monitoring (70% vs. 29%, P < 0.001). Symptom improvement/resolution occurred in 50–85% of patients without histological remission on PPI therapy. Six PPI‐REE patients demonstrated clinico‐histological relapse on PPI therapy.ConclusionsAt least one third of patients with suspected EoE achieve clinico‐histological remission on PPI therapy. Response is more limited in children compared with that in adults. pH monitoring does not accurately predict response to PPI therapy, albeit histological remission is significantly higher, up to 70%, upon documented GERD. Symptom improvement is common with PPI therapy despite persistent eosinophilic infiltration.