Background and Aims: We evaluated the effectiveness and safety of pan‐genotypic regimens, glecaprevir/pibrentasvir (GLE/PIB), sofosbuvir/velpatasvir (SOF/VEL), and sofosbuvir/daclatasvir (SOF/DCV) and other direct‐acting antivirals (DAA) regimens for the treatment of hepatitis C virus (HCV)‐infected adolescents (12–18 years), older children (6–11 years), and young children (3–5 years). The purpose of this systematic review and meta‐analysis was to inform the World Health Organization (WHO) guidelines. Methods: We included clinical trials and observational studies published up to August 11, 2021, that evaluated DAA regimens in HCV‐infected adolescents, older children, and young children. We searched MEDLINE, EMBASE, and CENTRAL databases and key conference abstracts. Sustained virological response 12 weeks after the end of treatment (SVR12), adverse events (AEs), and treatment discontinuation were the outcomes evaluated. Risk of bias was assessed using a modified version of the ROBINS‐I tool. Data were pooled using random‐effects models, and certainty of the evidence was assessed using the GRADE approach. Results: A total of 49 studies including 1882 adolescents, 436 older children, and 166 young children were considered. The SVR12 was 100% (95% Confidence Interval: 96–100), 96% (90–100), and 96% (83–100) for GLE/PIB in adolescents, older, and young children, respectively; 95% (90–99), 93% (86–98), and 83% (70–93), for SOF/VEL, respectively; and 100% (97–100) and 100% (94–100) for SOF/DCV in adolescent and older children, respectively. There was a clear trend towards a higher rate of any reported AE from adolescents (50%), older children (53%), to young children (72%). Serious AEs and treatment discontinuations were uncommon in adolescents and older children (<1%) but slightly higher in young children (3%). Conclusions: All three pan‐genotypic DAA regimens were highly effective and well‐tolerated and are now recommended by the WHO for use in adults, adolescents, and children down to 3 years, which will simplify procurement and supply chain management. The evidence was based largely on single‐arm non‐randomized controlled studies. Moreover, there were also missing data regarding key variables such as route of HCV acquisition, presence or absence of cirrhosis, or HIV co‐infection that precluded evaluation of the impact of these factors on outcomes. PROSPERO Record: CRD42020146752.

Scanty information on clustering longitudinal real-world data is available in the medical literature about the adherence implementation phase in rheumatoid arthritis (RA). To identify and characterize trajectories by analyzing the implementation phase of adherence to biologic Disease-Modifying Anti-Rheumatic Drugs (DMARDs), we conducted a retrospective cohort drug-utilization study using Tuscan administrative databases. RA patients were identified by a validated algorithm, including the first biologic DMARD supply from 2010 to 2015, RA specialist visit in the year before or after the first supply date and RA diagnosis in the five years before or in the year after the first supply date. We observed users for three years or until death, neoplasia, or pregnancy. We evaluated adherence quarterly through the Medication Possession Ratio. Firstly, we identified adherence trajectories and described the baseline characteristics; then, we focused on the trajectory most populated to distinguish the related sub-trajectories. We identified 952 first ever-biologic DMARD users in RA (712 females, mean age 52.7 years old, standard deviation 18.8). The biologic DMARD mostly supplied was etanercept (387 users) followed by adalimumab (233). Among 935 users with at least 3 adherence values, we identified 49 fully-adherent users, 829 continuous users, and 57 early-discontinuing users. Significant differences were observed among the index drugs. After focusing on the continuous users, three sub-trajectories were identified: continuous-steady users (556), continuous-alternate users (207), and continuous-declining users (66). No relevant differences emerged at the baseline. The majority of first ever-biologic DMARD users showed a continuous adherence behavior in RA. The role of adherence potential predictors and the association with effectiveness and safety outcomes should be explored by further studies.