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The Global world economy crisis had its roots in the Covid 19 pandemic. The key factors back then were a combination of the macroeconomic processes and initialization in micro economic financial levels. Global trade began to recover from the negative impacts brought by the COVID- 19 pandemic in June 2020. As it was obvious for the world’s financial economic institutions, the expectations after the pandemics were to overcome the economic crises and start the growth of the world trade markets. Instead of that in 2022 the Russian aggression on Ukraine has made the financial crisis even worse and bended the world on the knees. The world now lacks on gas, oil, grain and the most important electrical energy. Both Russia and Ukraine were and still are the global source raw material markets, especially for energy, food and fertilizers, but since the war has no looks on ending, the severe restrictions that are up for the world’s population may bring the worst still not expected rise of the financial crisis

Background Ozanimod (OZA) is approved in the EU, US, and other countries for the treatment of moderately to severely active ulcerative colitis (UC) in adults based on the phase 3 True North (TN) trial. Data on time to disease relapse in patients (pts) who withdrew OZA treatment in TN were previously reported (Sands BE et al. Am J Gastroenterol. 2022;17(suppl):S506-7). The objective of this post hoc analysis was to identify predictive and prognostic variables of time to disease relapse in the TN maintenance period (MP). Methods Pts in TN were randomised to once-daily oral OZA 0.92 mg or placebo (PBO) in a double-blind manner or to open-label OZA for a 10-week induction period. Those with clinical response to OZA at Week 10 were then rerandomised to continue OZA (OZA/OZA) or switch to PBO (OZA/PBO) in the MP. Disease relapse was defined as an increase in partial Mayo score of ≥2 points from Week 10, absolute partial Mayo score ≥4, Mayo endoscopy subscore (MES) ≥2, and exclusion of other causes of increased disease activity unrelated to UC. Time to disease relapse was estimated using the Kaplan-Meier method in both MP groups. The saturated Cox proportional-hazards model for assessing predictors of time to disease relapse included demographics, disease characteristics, prior medications, and laboratory and efficacy variables at the end of the induction period. Insignificant terms at α=0.05 were removed via backward elimination. Results The OZA/OZA arm (n=230) had a slightly higher proportion of pts with baseline severe endoscopic disease than the OZA/PBO arm (n=227). Otherwise, baseline and Week 10 characteristics were balanced across MP arms (Tables 1 and 2). In multivariable analyses, corticosteroid use at Week 10 was prognostic for time to relapse (P1 and clinical response but not remission at Week 10 were also assessed as prognostic variables, but these did not achieve statistical significance at α=0.05 (P=0.071 and P=0.171, respectively). Relapse rates were low and similar regardless of prior biologic exposure in the OZA/OZA arm. Prior biologic exposure was an independent predictor of time to relapse after withdrawal of OZA in the OZA/PBO arm (P=0.027) (Figure 1). For OZA/PBO pts, Week 16 Kaplan-Meier estimates and 95% CI of no relapse were 83.8% (76.7–88.8%), 72.1% (54.4–83.9%), and 48.5% (30.8–64.1%) for the biologic-naive, 1 failed biologic, and ≥2 failed biologics groups, respectively. Conclusion Increasing numbers of prior biologics were predictive of increased rates of disease relapse in pts who discontinued OZA. Pts with UC, especially those with prior biologic failures, should minimise OZA discontinuation to mitigate the risk of disease relapse.

Life insurance companies play a very important role in the financial sector. Life insurance provides individuals and the economy as a whole, a lot of important financial services. This is one of the main reasons for addressing this topic. In this paper is presented an overview of the progress of the development of the life insurance market among years and recently its trend and current position is shown. There are insurance companies that offer life insurance service in our country, their products are presented to detailed. There are several factors from different fields that directly or indirectly affect promoting the development of the life insurance market. They are presented explained and shown and their progress in parallel with the life insurance market. The special feature of this paper is an econometric study, which explains the relationship that exists between the credit factor mortgage and life insurance. The role of AMF, (Financial Supervision Agency), is mentioned as quite important in the development of the insurance market. The measures taken and targeted remain an objective quite important, on which the performance of the life insurance market depends.

Background Ozanimod (OZA), an oral sphingosine 1-phosphate receptor modulator that prevents lymphocyte migration to inflamed tissues, is approved for the treatment of patients with moderate to severe ulcerative colitis (UC) in the European Union and United States. The phase 3 True North (TN) randomised trial showed that OZA was effective and well tolerated in these patients. OZA efficacy in patients who have been exposed to vedolizumab (VDZ-exp), an integrin receptor antagonist that interferes with lymphocyte trafficking to the gut, has not yet been described. This post hoc analysis of TN examined OZA efficacy in VDZ-exp patients. Methods In TN, patients were randomised to oral once-daily OZA 0.92 mg (equivalent to OZA HCl 1 mg) or placebo (PBO; Cohort 1) or to open-label OZA (Cohort 2) during the induction period (IP). Patients with a clinical response to OZA at Week 10 were rerandomised to OZA or PBO in the maintenance period (MP). Efficacy at Week 10 (IP) and Week 52 (MP) in the VDZ-exp subgroup was calculated. Differences in proportions between OZA and PBO at Week 10 were based on the Cochran-Mantel-Haenszel (CMH) test, stratified by corticosteroid use at screening and prior anti-tumor necrosis factor (anti-TNF) use. Differences between OZA/OZA and OZA/PBO at Week 52 were based on the CMH test stratified by both remission status and corticosteroid use at Week 10. Results TN included a total of 185 VDZ-exp patients (Cohort 1: PBO, n=35; OZA, n=63; and Cohort 2: OZA, n=87). Baseline demographics and clinical characteristics were balanced across treatment groups. In the VDZ-exp subgroup, 52% of patients had extensive disease at baseline, 78% had a Mayo endoscopic score of 3, 85% were previously exposed to anti-TNF, and 61% were receiving corticosteroid at baseline. At Week 10, OZA (Cohort 1) was numerically more effective vs PBO for all endpoints in VDZ-exp pts (Figure 1A). Notably, in the subgroup of patients previously exposed to VDZ as a first-line advanced therapy, clinical response at Week 10 was achieved in 50% (6/12) of OZA pts in Cohort 1 and 42% (5/12) of OZA patients in Cohort 2. At Week 52, a higher proportion of VDZ-exp patients on continuous OZA achieved all efficacy endpoints vs the OZA/PBO group, with significant differences shown for most endpoints. OZA/OZA vs OZA/PBO differences at Week 52 were larger than OZA vs PBO differences at Week 10 (Figure 1B). Conclusion This post hoc analysis of the phase 3 TN study found that OZA was effective in UC patients who previously failed VDZ, including those who failed VDZ alone or following other advanced therapies. Future studies evaluating OZA in VDZ-exp patients are warranted.

Background The phase 3 True North randomised trial demonstrated the efficacy and safety of ozanimod (OZA) in patients with moderately to severely active ulcerative colitis (UC). Temporary discontinuation of UC treatment can occur in clinical practice. Understanding the duration of response after treatment discontinuation can assist in clinical decision making. This analysis examined time to loss of OZA response in patients who discontinued OZA and switched to placebo (PBO) in the True North maintenance period (MP). Methods In True North, patients were randomised to once-daily oral OZA 0.92 mg or PBO or to open-label OZA during a 10-week induction period (IP). Patients with clinical response to OZA at Week 10 were rerandomised to OZA (OZA/OZA) or PBO (OZA/PBO) in the MP through Week 52. Disease relapse was defined as an increase in partial Mayo score (PMS) of ≥2 points vs Week 10 with absolute PMS ≥4, endoscopic subscore ≥2, and exclusion of other causes of increased disease activity unrelated to UC. A subanalysis compared outcomes in OZA/OZA and OZA/PBO patients who entered the MP after achieving clinical remission (CRM) or clinical response (CRS only, excluding patients in CRM) at Week 10. Results In the True North MP, 230 patients continued OZA (CRM, n=82; CRS only, n=148) and 227 patients switched to PBO (CRM, n=79; CRS only, n=148). Baseline characteristics were generally similar between groups. Patients in CRS only at Week 10 had a numerically higher proportion with severe disease and prior immunosuppressive medication use vs CRM patients (Table). Differences in disease relapse between groups became apparent after MP Week 8, after which a significantly higher proportion of OZA/OZA patients were without relapse vs OZA/PBO patients (Figure). MP Week 42 Kaplan-Meier estimates of no relapse were 86.1% and 62.6% for OZA/OZA and OZA/PBO patients, respectively. Additionally, patients in CRM at Week 10 had higher rates of nonrelapse during the MP vs those in CRS only at MP entry. Kaplan-Meier estimates of nonrelapse at MP Week 42 were 67.9% and 59.7% in OZA/PBO patients with CRM and CRS, respectively, and 90.9% and 83.4% in OZA/OZA patients with CRM and CRS, respectively. Conclusion This analysis shows that OZA is effective at preventing disease relapse over 42 weeks of maintenance treatment in patients who achieve clinical response at Week 10. These data show that OZA maintains disease control even in the event of temporary discontinuation. However, extended discontinuation should be minimized in clinical practice.

We characterized the safety of first-line nivolumab plus ipilimumab (NIVO+IPI) in a large patient population with metastatic NSCLC and efficacy outcomes after NIVO+IPI discontinuation owing to treatment-related adverse events (TRAEs).We pooled data from three first-line NIVO+IPI studies (NIVO, 3 mg/kg or 240 mg every 2 wk; IPI, 1 mg/kg every 6 wk) in metastatic NSCLC (CheckMate 227 part 1, CheckMate 817 cohort A, CheckMate 568 part 1). Safety end points included TRAEs and immune-mediated adverse events (IMAEs) in the pooled population and patients aged 75 years or older.In the pooled population (N = 1255), any-grade TRAEs occurred in 78% of the patients, grade 3 or 4 TRAEs in 34%, and discontinuation of any regimen component owing to TRAEs in 21%. The most frequent TRAE and IMAE were diarrhea (20%; grade 3 or 4, 2%) and rash (17%; grade 3 or 4, 3%), respectively. The most common grade 3 or 4 IMAEs were hepatitis (5%) and diarrhea/colitis and pneumonitis (4% each). Pneumonitis was the most common cause of treatment-related death (5 of 16). Safety in patients aged 75 years or older (n = 174) was generally similar to the overall population, but discontinuation of any regimen component owing to TRAEs was more common (29%). In patients discontinuing NIVO+IPI owing to TRAEs (n = 225), 3-year overall survival was 50% (95% confidence interval: 42.6-56.0), and 42% (31.2-52.4) of 130 responders remained in response 2 years after discontinuation.First-line NIVO+IPI was well tolerated in this large population with metastatic NSCLC and in patients aged 75 years or older. Discontinuation owing to TRAEs did not reduce long-term survival.