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.

Intravenous and subcutaneous immunoglobulin replacement: a two-way road. Optimizing healthcare quality in patients with primary immunodeficiencies.

PURPOSE: To evaluate the alternate use of subcutaneous immunoglobulin (SCIG) and intravenous immunoglobulin (IVIG) in patients with primary immunodeficiencies (PID) in a third-level Pediatric University Hospital. METHODS: Retrospective study of all patients receiving SCIG from 2006 to 2012. Data collected included demographics, date SCIG was started, date of switch to IVIG and reasons, administration tolerance, and related adverse events. Effectiveness was defined as the lack of severe infections. RESULTS: Twenty-three patients (15 male, 8 female) with PID were studied. SCIG was initiated at a median age of 14.2 years (8.4 months-25.7 years) and median duration on SCIG treatment was 41 months (4-68). Nine patients (39.1%) temporarily switched from SCIG to IVIG for the following reasons: vacation (8), administration issues (1), and transient need for immunomodulatory therapy (1). A mean of 5.2 IVIG infusions/patient (SD=2.86) was administered while on SCIG. IVIG-related adverse events were documented in 3 patients with 6 infusions. Eight (34.8%) patients definitively discontinued SCIG use for the following reasons: convenience (5), adverse effects (1), coagulopathy (1), and autoimmune thrombocytopenia (1). There were no severe infections requiring hospital admission in any patient during the study period. CONCLUSIONS: Alternating SCIG and IVIG use in patients with PID was associated with considerable advantages in terms of convenience for the patients and their caregivers, while maintaining the effectiveness and safety of this therapy. Healthcare units treating these patients should show flexibility with this dual therapy in order to optimize patients' quality of life.