Otyłość a ryzyko rozwoju cukrzycy typu 2 i niektórych nowotworów złośliwych

  Obesity, type 2 diabetes mellitus and cancers are the most common chronic diseases. Data collected by world organizations for protection and promotion of health show a rapid increase in the prevalence of these illnesses over the last few decades. The rapid increase in prevalence of excess body weight globally is believed to be related to the growing proportion of people living in urban areas and the resulting changes in dietary and physical activity patterns. The epidemic of overweight and obesity and the clear connection between raised BMI and many non-communicable diseases (such as cardiovascular diseases, type 2 diabetes, and cancers) make this issue a public health priority all over the world. Estimates of future overweight and obesity prevalence assume that while keeping the current growth rate of prevalence, the numbers of people affected around the globe will rise to 2.16 billion for overweight and 1.12 billion for obesity in 2030. These numbers combined will constitute 58% of the world’s population. Considering the above, we should expect a proportional increase in prevalence of the most serious health consequences of overweight and obesity — type 2 diabetes mellitus and some cancers, including breast cancer in postmenopausal women, endometrial, colonic and renal cancers. In this paper we discussed the available data on prevalence of overweight and obesity and analysed a causal relationship between excess body weight, type 2 diabetes mellitus and selected types of malignancies.    Zarówno otyłość, jak i cukrzycę typu 2 oraz nowotwory złośliwe należy zaliczyć do najczęściej występujących obecnie schorzeń przewlekłych. Dane gromadzone przez światowe organizacje zajmujące się ochroną i promocją zdrowia wskazują na gwałtowny wzrost zapadalności na te choroby w ciągu ostatnich kilku dziesięcioleci. Przyczyn wzrostu rozpowszechnienia nadmiernej masy ciała na świecie upatruje się w zwiększającym się odsetku osób zamieszkujących tereny miejskie oraz wiążącym się z tym trybem życia. Wzrastający odsetek nadwagi oraz otyłości w populacji światowej oraz jej związek z występowaniem wielu schorzeń czyni je istotnym wyzwaniem dla zdrowia publicznego i priorytetem światowej polityki zdrowotnej. Prognozy dotyczące występowania nadwagi i otyłości zakładają, że przy utrzymaniu aktualnego tempa wzrostu rozpowszechnienia częstość ich występowania na świecie wzrośnie do 2,16 mld osób w przypadku nadwagi oraz 1,12 mld osób w przypadku otyłości w 2030 roku, co łącznie będzie stanowić 58% populacji świata. Mając na względzie powyższe dane, należy spodziewać się równie nasilonego wzrostu występowania najpoważniejszych konsekwencji zdrowotnych otyłości, jakimi są m.in. cukrzyca typu 2 oraz wybrane nowotwory złośliwe, w tym nowotwory piersi u kobiet będących po menopauzie, nowotwory endometrium, jelita grubego oraz nerki. W publikacji omówiono dostępne dane dotyczące epidemiologii oraz związku przyczynowo-skutkowego pomiędzy nadmierną masą ciała a ryzykiem rozwoju cukrzycy typu 2 oraz wybranych nowotworów złośliwych.

Atgam Efficacy and Safety in Moderate-to-Very Severe Acquired Aplastic Anemia: Outcome of a Large Multicenter Cohort of 634 Children and Adults from the French Authorization for Temporary Use Surveillance Program

International audienceIntroduction Acquired aplastic anemia (AA) is a rare immunological disease leading to bone marrow failure. First-line treatment in patients aged >40 years or without a matched related donor is immunosuppressive therapy (IST) based on anti-human T lymphocyte immunoglobulin (ATG) plus cyclosporine. This ATGAM Temporary Use Authorization program was a retrospective, multicenter study to report safety and efficacy surveillance data on ATGAM use in patients with AA. Methods This study collected surveillance data from the ATGAM Named Patients Program for French authorities ahead of ATGAM registration. Patients were treated with ATGAM 40 mg/kg for 4 days in addition to cyclosporine. Safety and efficacy data were collected from patients treated from September 2011 to August 2022 and reported to the French authority every 6 months. Patients were classified as severe AA if they had 2 of the following criteria: neutrophil count <0.5x10 9/L, platelet count <20x10 9/L, or reticulocyte count <60x10 9/L. Very severe AA: same as severe except neutrophil count <0.2x10 9/L. Patients not meeting criteria for very severe/severe AA were classified as moderate. Patient response was evaluated using the RACE study criteria (Peffault de Latour, et al [2022]), for severe AA: complete response was defined as: hemoglobin >100g/L, neutrophil count >1.0x10 9/L, and platelet count >100x10 9/L; partial response: no longer meeting criteria for severe disease; no response: still severe AA and/or transfusion dependent. For moderate AA (Marsh, et al [1999]), complete response was defined as: neutrophil count >2.0x10 9/L and platelet count >100x10 9/L; partial response: neutrophil count >1.0x10 9/L and platelet count >30x10 9/L; no response: transfusion dependent. Patients were classified as receiving first-line treatment (never received ATG), refractory (failed to respond to previous IST with ATG within 12 months before initial ATGAM), or relapse (recurrence of AA after a positive response to IST with ATG), regardless of AA severity. Results In total, 634 patients with moderate-to-very severe AA were treated with ATGAM (n=537 first-line; n=68 refractory/relapse; n=29 not classified) in addition to cyclosporine (40 first-line patients also received eltrombopag) from January 2012 to August 2022. By severity, n=124 were moderate, n=317 severe, n=133 very severe, and n=60 severity unknown. Patient demographics are shown in Table 1. Overall response (partial+complete) in patients on first-line therapy at 3, 6, and 12 months was 22.5% (n=78), 50.6% (n=156), and 79.2% (n=164), respectively. By severity, overall response rates in first-line therapy for moderate and severe/very severe cohorts, respectively, were: 25.0% (n=20) and 21.7% (n=58) at 3 months; 56.8% (n=42) and 48.7% (n=114) at 6 months; and 74.1% (n=40) and 81.0% (n=124) at 12 months. Overall response at 6 and 12 months by age and AA severity in patients on first-line treatment is shown in Table 2. Median duration of follow-up was 12.4 months. Overall survival (95% confidence interval) at 12 months for all patients was 91.5% (88.8-93.6). The treatment was well tolerated, and no new safety signals were observed with ATGAM. Cumulatively, 1,087 adverse events were reported in 364 patients over the entire program period, the majority of which were disease related. Conclusion This real-world, retrospective study utilizing surveillance data showed response rates in line with the recent RACE study (Peffault de Latour, et al [2022]) for patients with first-line severe AA treated with a combination of ATGAM and cyclosporine. No new safety risks were identified in this large cohort of patients. Treatment with ATGAM remains of benefit in patients with moderate-to-very severe AA

P776: ATGAM EFFICACY AND SAFETY IN MODERATE AND SEVERE ACQUIRED APLASTIC ANEMIA: OUTCOME OF A LARGE MULTICENTER COHORT OF 634 CHILDREN AND ADULTS FROM THE FRENCH AUTHORIZATION FOR TEMPORARY USE SURVEILLANCE PROGRAM

International audienceBackground: Acquired aplastic anemia (AA) is a rare immunological disease resulting in bone marrow failure. Patients can be treated either by immunosuppressive therapy (IST) or by allogeneic hematopoietic stem cell transplantation (HSCT). HSCT is the recommended treatment in patients younger than 40 years old with an available matched-related donor. IST is the recommended option for other patients: from the randomized trial published by Scheinberg in 2011, ATGAM® (horse anti-human T lymphocyte immunoglobulin) in addition to cyclosporine was the reference first-line IST for moderate to severe AA.Aims: This retrospective, multicentric study was conducted to report safety and efficacy data from ATGAM use in patients with AA utilizing surveillance data.Methods: This Temporary Use Authorization (ATU) program was initiated to collect surveillance data from the ATGAM Named Patients Program for French authorities before ATGAM was registered. This is the final report from this program. Safety and efficacy data was collected from the program and reported every 6 months. ATGAM was dosed at 40 mg/kg for 4 days in all patients that received treatment. Severity of AA was classified according to Camitta and EBMT scores. Response criteria followed the British Committee for Standards in Haematology Guidelines. For severe AA, no response: still severe; partial response: transfusion independence and the patient no longer met criteria for severe disease; complete response: hemoglobin was normal, neutrophil count >1.5x109/L, and platelet count >150x109/L. For moderate AA: no response: worse or did not meet criteria for response that included transfusion independence (if previously dependent) or doubling or normalization of at least 1 cell line or an increase of baseline hemoglobin, or an increase of baseline neutrophils or increase of baseline; complete response: the same criteria as for severe AA.Results: 634 patients (including 148 children) with moderate to very severe AA received ATGAM (n=537 first line; n=68 refractory/relapse; n=29 not classified) in addition to cyclosporine from January 2012 to August 2022. Overall hematologic response (Complete + Partial) at 6 months was 62.3% in the combined population. By severity, response rates were 84.4%, 50.8%, and 36.4% among patients with moderate, severe, and very severe AA, respectively, receiving first-line therapy (n=537; Table). By age, response rates were respectively 54.3%, 65.2%, and 64.4% in children (≤17 years), adults (≥18-<65 years), and elderly (≥65 years) patients. The overall survival rate (95% confidence interval) at 3 years was 96.9% (91.9-98.8%) in children, 83.4% (77.1-88.1%) in adults, and 79.7% (65.9-88.3%) in elderly patients. Treatment was well tolerated for the majority of patients. In total, 1087 adverse events (485 serious adverse events) were reported, with 48 fatal events.Summary/Conclusion: Reported response rate and overall survival in this real-life surveillance study are in line with a 2011 randomized controlled study comparing horse versus rabbit ATG (Scheinberg, et al [2011]) and control group of the most recent study RACE (Peffault de Latour, et al [2022]). The relatively large number of patients in this study compared with other similar studies in patients with AA adds to the robustness of this real-world data study. No new safety risks were identified, and this study showed that use of ATGAM remains favorable in this patient population