darbepoetin alfa (Darbecure)

Comparison of Peg-INF plus TDF versus TDF Monotherapy in Indeterminate-phase Chronic Hepatitis B Patients with High HBsAg levels, HBeAg-negative status, and Normal ALT Levels.

Liu Min M, Xiao An A, Bu Bing B, Zuo Lili L et al.

Chronic hepatitis B patients with baseline hepatitis B surface antigen (HBsAg) <1500 IU/mL are considered as the favorable population for achieving functional cure. This trial aimed to explore a treatment strategy to help the unfavorable population characterized by high HBsAg levels (>3000 IU/mL), hepatitis B e antigen-negative status, and normal alanine transaminase levels in the indeterminate phase (HBeIP), transition to the favorable group. In this investigator-initiated, open-label clinical trial, we randomly assigned participants aged 18 to 60 years with HBeIP characteristics to receive either tenofovir disoproxil fumarate (TDF) monotherapy (monotherapy group) or pegylated interferon alfa-2b (Peg-IFNα-2b) plus TDF (combination group). The primary endpoints were the HBsAg loss rate and the proportion of participants with HBsAg <1,500 IU/mL through week 96. From May 2021 to November 2023, we enrolled 263 participants, with 131 randomly assigned to the combination group and 132 to the monotherapy group. In the primary analysis, none of the 132 participants (0%) in the monotherapy group achieved HBsAg loss, compared with 10 of 131 (7.6%) in the combination group (P = 0.001). Through week 96, 48.9% (64/131) of participants in the combination group achieved HBsAg <1,500 IU/mL, and a reduction in HBsAg level greater than 1 log10 IU/mL between baseline and week 24 was an independent predictor of this endpoint (Odds Ratio = 16.957, 95% Confidence Interval: 3.002-95.797, P = 0.001). In contrast, only two participants (1.5%) in the monotherapy group achieved HBsAg <1,500 IU/mL. Compared with TDF monotherapy, combination therapy with Peg-IFNα-2b and TDF significantly improved both HBsAg <1,500 IU/mL and HBsAg loss rates in HBeIP patients.

Protective effects of hesperidin against nano-alumina in the rat brain: Bioaccumulation, oxidative stress, and inflammatory biomarkers.

El-Gridly Dina M DM, Ezzat Ahmed R AR, Mohammed Haitham S HS, Morsy Gamal M GM

The protective efficiency of hesperidin (Hesp) against the bioaccumulation and neurotoxicity induced by nano-alumina (Al2O3NPs) in three brain regions (BR), hippocampus (Hippo), cortex (Cor), and brainstem (BS), has been investigated in rats. The study comprised a 30-day pre-treatment period followed by 7- and 14-days experimental periods (EP) of treatments (T). Rats were divided into four groups: Group I received de-ionized water (DW) daily via both intranasal and oral routes throughout the pre-treatment and T. Group II was administered intranasal DW daily during the pre-treatment period, followed by intranasal Al2O3NPs every other day during the T. Group III was administered oral Hesp daily during both the pre-treatment and T. Group IV received a daily oral Hesp during the pre-treatment. During the T, rats were given an intranasal Al2O3NPs every other day alongside a daily oral dose of Hesp. Animal sacrifice and tissue collection occurred on day 7 and day 14 of the T. The results showed a significant increase in aluminum (Al3+) ion accumulation in all BR of Group II as compared with the three other groups. In Group II, the levels of iron (Fe2+), zinc (Zn2+), glutathione (GSH), as well as the activities of superoxide dismutase (SOD) and catalase (CAT) were significantly decreased. Tumor necrosis factor-alfa (TNF-α) and interleukin-6 (IL-6) were markedly elevated in this group. Significant inverse correlations were observed between Al3+ ion accumulation and the levels of Fe2+, Zn2+, GSH, as well as the activities of SOD and CAT. In contrast, a significant positive correlation was found between Al3+ accumulation and TNF-α and IL-6 levels. In conclusion, co-administration of Hesp with Al2O3NPs reduced the neurotoxic effects of Al2O3NPs. The present findings suggest that Hesp protected against Al2O3NPs-induced neurotoxicity by limiting Al3+ ion bioaccumulation, thereby alleviating oxidative stress and inflammation.

Evaluating Costs and Efficacy of rFVIII Prophylaxis Using Matching-Adjusted Indirect Comparisons in Hemophilia A.

Kessler Craig M CM, Mannucci Pier M PM, Jiménez-Yuste Victor V, Frenzel Laurent L et al.

Introduction Prophylaxis with factor VIII (FVIII) is the standard of care for individuals with severe hemophilia A, but it is associated with a substantial economic burden. This analysis compared the efficacy, dosing, and annual treatment costs of simoctocog alfa (Nuwiq, a recombinant FVIII [rFVIII]) with five extended half-life (EHL) rFVIII concentrate products. Methods Matching-adjusted indirect comparisons (MAICs) were performed to compare simoctocog alfa with efanesoctocog alfa (ALTUVIIIO) and turoctocog alfa pegol (Esperoct), and results were integrated with a previously published MAIC comparing simoctocog alfa with efmoroctocog alfa (ELOCTATE), damoctocog alfa pegol (JIVI), and rurioctocog alfa pegol (ADYNOVATE). These MAIC-adjusted populations were used to develop a cost model from a United States payer perspective. Results Annual total costs per person were $147,058 to $492,090 lower with simoctocog alfa compared with EHL rFVIII products, corresponding to a 21% to 46% cost reduction, primarily driven by lower drug acquisition costs. Outcomes were comparable or favorable to simoctocog alfa versus turoctocog alfa pegol, efmoroctocog alfa, damoctocog alfa pegol, and rurioctocog alfa pegol. In comparison with efanesoctocog alfa (Group A), no significant differences were observed in the proportion of individuals with zero bleeds, whereas treated total annualized bleeding rate (ABR) and treated spontaneous ABR favored efanesoctocog alfa. Conclusion This indirect comparison suggests that personalized prophylaxis with simoctocog alfa may offer economic advantages versus EHL rFVIII products in individuals with severe hemophilia A. Clinical outcomes were broadly comparable across comparators, although treated total and spontaneous ABRs were significantly lower with efanesoctocog alfa (Group A).

Ropeginterferon alfa-2b in mycosis fungoides: A multicentre cohort.

Nikolaou Vasiliki V, Koumprentziotis Ioannis-Alexios IA, Konstantinou Iliana I, Iliakis Theodoros T et al.