Discussion
TB, RA, infections, VTEs, lung cancer, infection, malignancies, deaths
RENAL CANCER, DISEASE, INFECTIONS, LUNG CANCER, MALIGNANCIES, INFECTION, LYMPHOMA, EVENTS
Based on an integrated safety analysis of patients from the SELECT clinical trial program, the overall safety profile of upadacitinib 15 mg QD appears comparable between the LATAM and the RoW populations. Rates of AEs and deaths were similar for both populations, although the rates of SAEs and AEs leading to discontinuation were lower in the LATAM patients. The most common AESIs in the LATAM population were infections, including serious infections and HZ, and laboratory abnormalities, which is consistent with the known safety profile of upadacitinib [During the analysis of the long-term data with the totality of the upadacitinib phase 3 program in RA, age ≥ 75 years and smoking increased the risk of serious infection for upadacitinib [Rates of TB are known to be higher in LATAM compared with North America and Europe [HZ is a known risk in patients with RA receiving JAKis, including upadacitinib, and a previous analysis has shown that Asian patients receiving upadacitinib were at greater risk of HZ compared with patients in other regions [While overall the risk of malignancies is not increased in patients with RA, certain malignancies (such as lung cancer, renal cancer, and lymphoma) do occur at an increased rate [A meta-analysis of observational studies has found a 50% increased risk of CV disease in patients with RA compared with the general population; in a large, international cohort of patients, 30% of CV events were attributable to RA characteristics, and 49% were attributable to CV risk factors [Compared with the general population, patients with RA have an increased risk of developing VTEs (0.1 to 0.4 events per 100 PY vs 0.3 to 0.7 events per 100 PY) [Changes in laboratory parameters, including decreases in neutrophil and lymphocyte counts and increases in transaminases and CPK, are consistent with previous JAKi findings [One limitation of this study is that the data were pooled from six different clinical trials, and LATAM countries did not participate in the SELECT-BEYOND study. In addition, this is a post hoc analysis of randomized clinical trials that were not designed to compare LATAM and RoW data. As such, the number of LATAM patients and their overall time of exposure to upadacitinib 15 mg QD are lower than in the RoW population. This limits interpretation of the data and the identification of any differences between populations. Safety data in LATAM patients are therefore subject to varying patient populations, including differences in previous and failed treatments, comorbidities, and different concomitant therapies. In addition, the limited PBO exposure in the SELECT trials did not allow a PBO-controlled analysis of long-term safety; we were also unable to assess the safety of upadacitinib vs active comparators such as MTX, ABA, and ADA in LATAM patients due to relatively low patient numbers. Moreover, as each study had specific follow-up protocols and eligibility criteria, generalizability of these results to clinical practice may be limited. Despite these limitations, the results obtained provide valuable information about the safety of upadacitinib treatment in LATAM patients with RA.In conclusion, based on integrated safety data from six phase 3 trials, there is a consistent safety profile with upadacitinib 15 mg QD for the treatment of RA in the LATAM population compared with the RoW. These results support an acceptable safety profile of upadacitinib 15 mg QD for the treatment of moderately to severely active RA in adult patients in LATAM.