Are all JAK inhibitors for the treatment of rheumatoid arthritis equivalent? An adjusted indirect comparison of the efficacy of tofacitinib, baricitinib, upadacitinib, and filgotinib.

INTRODUCTION: Comparisons of Janus kinase inhibitors (JAKi) for treatment of rheumatoid arthritis in patients with inadequate response to biologic disease-modifying anti-rheumatic drugs are lacking. We assessed the relative efficacy and safety of four JAKi (tofacitinib, baricitinib, upadacitinib, and filgotinib) in this context. METHOD: We performed an adjusted indirect comparison (IC) of randomized clinical trials using Bucher's method with an IC and mixed calculator. Endpoints were Disease Activity Score C-reactive protein (DAS28-CRP) and American College of Rheumatology-20 (ACR20). Equivalence was assessed using the equivalent therapeutic alternatives (ETA) guidelines. RESULTS: We included four of 133 potentially relevant studies. IC showed no statistically significant differences between the four JAKi regarding DAS28-CRP < 3.2. Results were similar in terms of ACR20 except for tofacitinib showing lower efficacy than upadacitinib (RAR -18.4% [IC95% -33.4 to -3.5], p=0.0157). Statistically significant differences were related to the relevant difference for tofacitinib in both endpoints. Despite no statistical differences for baricitinib, we observed a probably clinically relevant difference regarding DAS28-CRP. Probably clinically relevant differences were found for tofacitinib vs. upadacitinib in both endpoints, and for baricitinib vs. upadacitinib in DAS28-CRP. Safety, drug-drug interactions, and convenience considerations did not modify the result of therapeutic equivalence assessment based on efficacy data. CONCLUSIONS: In conclusion, our results show that filgotinib and upadacitinib are ETA. Baricitinib and upadacitinib are also ETA due to a lack of clear differences and for showing superiority over placebo. The results for tofacitinib and upadacitinib show some inconsistency and more data are needed. Key Points • To date, neither a head-to-head comparison nor an indirect comparison between the Janus kinase inhibitors has been performed in patients with rheumatoid arthritis and an inadequate response to biologic disease-modifying anti-rheumatic drugs. • We performed an adjusted indirect comparison that included randomized clinical trials of tofacitinib, baricitinib, upadacitinib, and filgotinib to assess their equivalence in this scenario. • Our results show that baricitinib and filgotinib are equivalent therapeutic alternatives compared to upadacitinib. However, there is some inconsistency in the results of tofacitinib in front of upadacitinib.

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.