Exposure-efficacy and exposure-safety analyses of ropeginterferon alfa-2b treatment in patients with polycythaemia vera.

AIMS: To investigate the exposure-response (E-R) relationship, including exposure-efficacy and exposure-safety, of ropeginterferon alfa-2b treatment in patients with polycythaemia vera (PV). METHODS: Based on the results of the phase II trial A20-202 regarding ropeginterferon alfa-2b in patients with PV, E-R analyses were performed to evaluate the efficacy and safety of the given dosing regimen. The E-R analyses were based on logistic and linear regression and the relationship between exposure to ropeginterferon alfa-2b and key efficacy and safety variables. The key efficacy variables included complete haematologic response (CHR) and reduction of the driver mutation JAK2V617F. The safety variable was treatment-related adverse events (TRAEs). RESULTS: A clear relationship between the exposure to ropeginterferon alfa-2b and CHR was observed, with an increase in drug exposure resulting in an increased probability of achieving CHR. Similar CHR probabilities were observed in the third and fourth quantiles of the average concentration at Week 24. The results from the exposure-JAK2V617F model indicated that the JAK2V617F allele burden decreased with increasing exposure to ropeginterferon alfa-2b and baseline body surface area. Exposure-safety analysis revealed a risk of AEs associated with transaminase abnormalities, which were not associated with clinical significance. CONCLUSIONS: Our analyses have shown that patients with PV treated with ropeginterferon alfa-2b had an increased probability of achieving CHR and a molecular response with acceptable safety risks at the 250-350-500 µg titration dosing regimen. This study has provided the relevant data for the application of a biologics licence of ropeginterferon alfa-2b for PV treatment in China.

Mapping out the surgical anatomy of the lingual nerve: a systematic review and meta-analysis.

Objectives: Understanding the lingual nerve's precise location is crucial to prevent iatrogenic injury. This systematic review seeks to determine the lingual nerve's most probable topographical location in the posterior mandible. Materials and Methods: Two electronic databases were searched, identifying studies reporting the lingual nerve's position in the posterior mandible. Anatomical data in the vertical and horizontal dimensions at the retromolar and molar regions were collected for meta-analyses. Results: Of the 2,700 unique records identified, 18 studies were included in this review. In the vertical plane, 8.8% (95% confidence interval [CI], 1.0%-21.7%) and 6.3% (95% CI, 1.9%-12.5%) of the lingual nerves coursed above the alveolar crest at the retromolar and third molar regions. The mean vertical distance between the nerve and the alveolar crest ranged from 12.10 to 4.32 mm at the first to third molar regions. In the horizontal plane, 19.9% (95% CI, 0.0%-62.7%) and 35.2% (95% CI, 13.0%-61.1%) of the lingual nerves were in contact with the lingual plate at the retromolar and third molar regions. Conclusion: This systematic review mapped out the anatomical location of the lingual nerve in the posterior mandible, highlighting regions that warrant additional caution during surgeries to avoid iatrogenic lingual nerve injuries.

Clinical Experience with Ropeginterferon Alfa-2b in the Off-Label Use for the Treatment of COVID-19 Patients in Taiwan.

INTRODUCTION: This study, for the first time to our knowledge, evaluated the efficacy of ropeginterferon alfa-2b, a long-acting pegylated interferon (IFN)-alfa, in the treatment of COVID-19. METHODS: We retrospectively evaluated ropeginterferon alfa-2b administered subcutaneously at a single dose of 250 µg for the treatment of mild and moderate COVID-19. Primary outcome was to compare the overall negative conversion time from the confirmed, last positive SARS-CoV-2 RT-PCR to the first RT-PCR negative conversion between patients receiving ropeginterferon alfa-2b plus standard of care (SOC) and those receiving SOC alone. RESULTS: Thirty-five patients with mild COVID-19 and 37 patients with moderate disease were included. Of them, 19 patients received SOC plus ropeginterferon alfa-2b and 53 patients received SOC alone. All patients with moderate disease in the ropeginterferon alfa-2b group showed RT-PCR negative conversion within 8 days, while a significant portion of patients in the SOC alone group failed to do so. For patients with moderate disease and age ≤ 65 years old, the ropeginterferon alfa-2b group had statistically significant shorter median RT-PCR conversion time than the SOC alone group (7 vs. 11.5 days, p < 0.05). CONCLUSIONS: Ropeginterferon alfa-2b showed the potential for the treatment of moderate COVID-19 patients. A randomized, controlled Phase III study is planned to further assess the effectiveness of ropeginterferon alfa-2b in COVID-19 patients.