Impact of rituximab biosimilars on overall survival in diffuse large B-cell lymphoma: a Dutch population-based study.

In 2017, the European Medicines Agency approved rituximab biosimilars (R-biosimilars) for treatment of diffuse large B-cell lymphoma (DLBCL). Thereafter, the Netherlands was one of the first countries to implement R-biosimilars, given lower costs compared with rituximab originator (R-originator). This study's objective was to investigate whether overall survival (OS) of patients with DLBCL receiving R-biosimilars is similar to patients treated with R-originator. DLBCL patients ≥18 years, diagnosed between 2014 and 2018, who received at least 1 cycle of rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) were identified in the Netherlands Cancer Registry. Patients were categorized into R-originator or R-biosimilars groups based on data from a central repository of the Dutch medicinal drug market. The primary end point was 3-year OS, defined as the time between diagnosis and all-cause death. By the end of 2018, 91% of purchased rituximab were biosimilars. In total, 4429 patients were identified with 876 in the R-biosimilars group and 3553 in the R-originator group. Patients in the R-biosimilars group less frequently received >6 cycles of R-CHOP compared with patients treated with R-originator (24% vs 30%, P = .003). The 3-year OS did not differ between patients treated with R-originator or R-biosimilars (73% vs 73%, P = .855). This was confirmed with a multivariable Cox regression analysis accounting for sex, age, International Prognostic Index score, and number of R-CHOP cycles. In conclusion, the 3-year OS is similar for patients treated with CHOP in combination with R-originator or R-biosimilars and, therefore, favors the use of R-biosimilars in DLBCL treatment management.

Long-term changes in dysnatremia incidence in the ICU: a shift from hyponatremia to hypernatremia.

BACKGROUND: Dysnatremia is associated with adverse outcome in critically ill patients. Changes in patients or treatment strategies may have affected the incidence of dysnatremia over time. We investigated long-term changes in the incidence of dysnatremia and analyzed its association with mortality. METHODS: Over a 21-year period (1992-2012), all serum sodium measurements were analyzed retrospectively in two university hospital ICUs, up to day 28 of ICU admission for the presence of dysnatremia. The study period was divided into five periods. All serum sodium measurements were collected from the electronic databases of both ICUs. Serum sodium was measured at the clinical chemistry departments using standard methods. All sodium measurements were categorized in the following categories: <120, 120-124, 125-129, 130-134, 135-139, 140-145, 146-150, 151-155, 156-160, >160 mmol/L. Mortality was determined at 90 days after ICU admission. RESULTS: In 80,571 ICU patients, 913,272 serum sodium measurements were analyzed. A striking shift in the pattern of ICU-acquired dysnatremias was observed: The incidence of hyponatremia almost halved (47-25 %, p < 0.001), whereas the incidence of hypernatremia nearly doubled (13-24 %, p < 0.001). Most hypernatremias developed after ICU admission, and the incidence of severe hypernatremia (sodium > 155 mmol/L) increased dramatically over the years. On ICU day 10 this incidence was 0.7 % in the 1992-1996 period, compared to 6.3 % in the 2009-2012 period (p < 0.001). More severe dysnatremia was associated with significantly higher mortality throughout the 21-year study period (p < 0.001). CONCLUSIONS: In two large Dutch cohorts, we observed a marked shift in the incidence of dysnatremia from hyponatremia to hypernatremia over two decades. As hypernatremia was mostly ICU acquired, this strongly suggests changes in treatment as underlying causes. This shift may be related to the increased use of sodium-containing infusions, diuretics, and hydrocortisone. As ICU-acquired hypernatremia is largely iatrogenic, it should be-to an important extent-preventable, and its incidence may be considered as an indicator of quality of care. Strategies to prevent hypernatremia deserve more emphasis; therefore, we recommend that further study should be focused on interventions to prevent the occurrence of dysnatremias during ICU stay.