The Pohang quake shows the need for new methods to assess and manage evolving risk

ObjectiveTo demonstrate pharmacokinetic equivalence of CT-P10 and innovator rituximab (RTX) in patients with rheumatoid arthritis (RA) with inadequate responses or intolerances to antitumour necrosis factor agents.MethodsIn this randomised phase I trial, patients with active RA were randomly assigned (2:1) to receive 1000 mg CT-P10 or RTX at weeks 0 and 2 (alongside continued methotrexate therapy). Primary endpoints were area under the serum concentration–time curve from time zero to last quantifiable concentration (AUC0–last) and maximum serum concentration after second infusion (Cmax). Additional pharmacokinetic parameters, efficacy, pharmacodynamics, immunogenicity and safety were also assessed. Data are reported up to week 24.Results103 patients were assigned to CT-P10 and 51 to RTX. The 90% CIs for the ratio of geometric means (CT-P10/RTX) for both primary endpoints were within the bioequivalence range of 80%–125% (AUC0–last: 97.7% (90% CI 89.2% to 107.0%); Cmax: 97.6% (90% CI 92.0% to 103.5%)). Pharmacodynamics and efficacy were comparable between groups. Antidrug antibodies were detected in 17.6% of patients in each group at week 24. CT-P10 and RTX displayed similar safety profiles.ConclusionsCT-P10 and RTX demonstrated equivalent pharmacokinetics and comparable efficacy, pharmacodynamics, immunogenicity and safety.Trial registration numberNCT01534884.

Hydraulic injection by the Pohang enhanced geothermal systems (EGSs) has been suspected to trigger the 2017 moment magnitude (MW) 5.5 Pohang earthquake in South Korea. The last stimulation experiment in the EGS was conducted only 2 months before the disaster, which has led to this suspicion. In this study, we conducted a seismic analysis on the earthquakes that have occurred around the EGS site in the past 10 years. The study included the construction of a velocity model, earthquake detection, the determination of hypocenters, magnitudes, focal mechanisms, and stress inversion, and a clustering analysis. No seismic activity was detected near the study area until November 2015 when there was a loss of a large quantity of heavy drilling mud. For three stimulations of a geothermal well, earthquakes sequentially migrated to the southwest along a fault plane, leading to the location of the mainshock. The delineated fault plane crossed the injection well at approximately 3,800 m, which corresponds to the borehole interval of not only the mud loss but also the breakage of the well's casing due to the mainshock rupture. These findings can be treated as empirical evidence for the hypothesis that the 2017 MW 5.5 Pohang earthquake was initiated on a critically stressed fault zone by the anthropogenic activity of fluid injection, consequentially releasing accumulated strain energy via tectonic loading.

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