Incidence Rates Of Malignancies Research Articles

Evolving epidemiology of NAFLD in South Korea: incidence, prevalence, progression, and healthcare implications from 2010 to 2022.

Non-alcoholic fatty liver disease (NAFLD), now the most common chronic liver worldwide, has become a significant public health concern. This study aims to analyze the evolving epidemiology of NAFLD in South Korea. We utilized claim data from the Korean National Health Insurance Service from 2010 to 2022 to analyze NAFLD's incidence, prevalence, and progression. From 2010 to 2022, the incidence and prevalence rates of NAFLD each increased from 1.87% to 4.47% and from 10.49% to 17.13%, respectively. The differences in prevalence rates between urban and rural areas were minimal in 2012 and 2022, yet both areas showed significant increases in the prevalence of NAFLD over the decade. The NAFLD group had a higher prevalence of comorbidities compared to the control group, and the most common comorbid condition was hypertension. Moreover, the ten-year incidence rates of malignancy, heart disease, and stroke in the NAFLD group were 13.42%, 15.72%, and 8.36%, respectively, which were significantly higher than those in the control group. The incidence rates of cirrhosis and hepatocellular carcinoma in NAFLD over 10 years were 2.22% and 0.77%, respectively. The total medical costs of NAFLD patients more than doubled over ten years and were all significantly higher than those of the control group. A significant increase in NAFLD prevalence and its impact on healthcare utilization was observed in South Korea. With NAFLD leading to serious liver diseases and increased healthcare costs, integrated care strategies that include both medical treatment and lifestyle modifications are essential.

Geographical Differences in the Safety and Efficacy of Tofacitinib Versus TNFi: APost Hoc Analysis of ORAL Surveillance.

In ORAL Surveillance, incidence rates (IRs) of major adverse cardiovascular events (MACE) and malignancies (excluding non-melanoma skin cancer [NMSC]) in cardiovascular (CV)-risk-enriched patients with rheumatoid arthritis (RA) were numerically greater with tofacitinib in North America versus the rest of the world, due to underlying risk factors. Here, we evaluated the safety and efficacy of tofacitinib versus tumor necrosis factor inhibitors (TNFi) among patients with RA across geographical regions. Patients with RA in ORAL Surveillance (NCT02092467), who were aged ≥ 50years with ≥ 1additional CV risk factor, received tofacitinib 5 or 10mg twice daily or TNFi; 45.9% were from either Poland or North America. This post hoc analysis stratified patients by region (Poland, North America, Other countries). Efficacy endpoints included Clinical Disease Activity Index, Disease Activity Score in 28 joints, with C-reactive protein (DAS28-4[CRP]), and Health Assessment Questionnaire-Disability Index (HAQ-DI). IRs and hazard ratios for adverse events were reported. Of 4362 patients (Poland, N = 759; North America, N = 1243; Other countries, N = 2360), more patients from North America versus Poland/Other countries had CV risk factors such as body mass index ≥ 30kg/m2 and history of diabetes/hypertension; however, more patients from Poland versus other regions were ever smokers and more patients from Poland/North America versus Other countries had history of coronary artery disease. MACE IRs were similar in North America and Poland, and numerically higher versus Other countries. IRs for malignancies (excluding NMSC) were numerically higher in NorthAmerica versus Poland/Other countries with tofacitinib. Serious infections IRs werenumerically higher in North America versus Poland across treatments. Venousthromboembolism/all-cause mortality IRs were generally comparable across regions. DAS28-4(CRP)/HAQ-DI improvements were generally lowest in North America. Differences in safety outcomes were driven by the presence of baseline risk factors; North America and Poland demonstrated a higher proportion of patients with some baseline CV risk factors/comorbidities versus Other countries. NCT02092467 (ClinicalTrials.gov).

Incidence of Malignancies and the Association with Biological Disease-Modifying Antirheumatic Drugs in Japanese Patients with Rheumatoid Arthritis: A Time-Dependent Analysis from the IORRA Patient Registry.

Patients with rheumatoid arthritis (RA) may have an increased malignancy risk versus the general population, potentially elevated by biological disease-modifying antirheumatic drug (bDMARD) use. Using patient registry data, we determined malignancy risk, stratified by bDMARD use, among Japanese patients with RA versus the Japanese general population and investigated whether bDMARD use is a time-dependent risk factor for the development of malignancy. Patients aged ≥ 18years with ≥ 2 data entries of RA in the IORRA (Institute of Rheumatology, Rheumatoid Arthritis) patient registry, enrolled from January 2013-December 2018, were identified ('All RA' cohort). Patients were stratified into bDMARD (≥ 1bDMARD received) or non-bDMARD (no history of bDMARDs) sub-cohorts. Malignancy incidence rates and standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) versus the Japanese general population were calculated. Risk of RA medication use was analyzed using a time-dependent Cox proportional hazards model, after adjusting for covariates. A total of 8020 patients were identified for the All RA cohort; 2187 and 5833 for the bDMARD and non-bDMARD sub-cohorts, respectively. For all three cohorts, incidence of overall malignancies was similar versus the Japanese general population. Incidence of specific malignancies was also similar, but incidence of lymphoma was higher for all three cohorts (SIRs[95% CIs] 3.72 [2.71-4.93], 5.97 [3.34-9.59], and 2.79 [1.82-4.02], respectively). In the bDMARD sub-cohort, no increase in SIRs was observed for other site-specific malignancies. Inthe All RA cohort, use of methotrexate, tacrolimus, glucocorticoids, non-steroidal anti-inflammatory drugs, and bDMARDs were not associated with the risk of overall malignancy; the hazard ratio (95% CI) was 1.36(0.96-1.93) for bDMARD use. Increased disease activity was a time-dependent risk factor of overall malignancy with a hazard ratio (95% CI) of 1.35 (1.15-1.59). The use of bDMARDs was not a time-dependent risk factor for malignancy.

Rheumatoid arthritis reduces the risk of colorectal cancer through immune inflammation mediation.

There is a close relationship between immune-mediated inflammation and cancer, and there is still controversy over whether rheumatoid arthritis (RA) increases the risk of malignancy. We first used Mendelian randomization (MR) analysis to explore the potential causal relationship between RA and pan-cancer. And verify the effect of immune-mediated inflammation on cancer through intermediate MR analysis. Then we extracted the standardized incidence rate of malignancy in RA patients relative to the general population through large-scale meta-analysis. Finally, we performed pan-cancer analysis on the RA related genes obtained from MR analysis. And perform immune related analysis on key genes to reveal the association between RA and malignancy. The MR analysis demonstrated a negative correlation between RA and pan-cancer (p = 0.008). Autoimmune traits were the main mediating variable for the causal relationship between RA and pan-cancer. Based on the results of the meta-analysis, we validated that RA reduces the risk of developing colorectal cancer (SIR = 0.69, 95% CI 0.53-0.85). Pan-cancer analysis also showed that high expression of RA related genes was negatively correlated with colon adenocarcinoma. IL6R was the gene with the highest correlation among them, and its correlation with immune cells was higher in colorectal cancer than in other malignancy. Our MR study provides evidence that RA was associated with reduced risk of colorectal cancer. This effect is caused by immune-mediated inflammation, with IL6R being a key regulatory gene.

The CLARION study: first report on safety findings in patients newly initiating treatment with cladribine tablets or fingolimod for multiple sclerosis

Objectives: As part of the CLARION study: (1) characterize the incidence of severe infections, herpes zoster, and malignancies in patients newly initiating cladribine or fingolimod for relapsing multiple sclerosis (MS); (2) estimate the incidence of severe lymphopenia among cladribine users; and (3) describe prior/subsequent disease-modifying therapy (DMT) in both cohorts. Methods: Patients were identified from seven participating MS registries/data sources. The incidence rate (IR) of each outcome per 1000 patient-years and its 95% confidence interval (95%CI) were estimated for cohorts using Poisson regression. Results: By cut-off date (01-April-2020), 742 cladribine and 867 fingolimod users were included. Mean follow-up was ∼1 year. The IR for severe infections from all contributing sources (except Denmark) was: cladribine, 7.37 (2.76,19.6); fingolimod, 6.55 (2.46,17.4). The corresponding IR for herpes zoster was 5.51 (1.78,17.1) and 3.27 (0.82,13.1), respectively, while values for opportunistic infections were 0 (0,6.76) and 1.63 (0.23,11.6), respectively. There were no events of progressive multifocal leukoencephalopathy in either cohort. The IR of severe lymphopenia was 63.9 (40.7,100.1) in 349 cladribine users from contributing sources. The IR of malignancies (cut-off date 01-April-2022) was 3.55 (1.59,7.90) for the cladribine cohort (N = 1035) and 3.55 (1.48,8.52) for the fingolimod cohort (N = 843) from three MS registries/data sources. In the combined data sources, 36.8% of cladribine and 27.4% of fingolimod users were DMT-naïve; after initiation of study treatment, 2.5% and 20.2% switched to another DMT, respectively. Conclusion: No new safety signal was observed in patients treated with cladribine tablets, although results are limited by a relatively short duration of follow-up.

Upper and Lower Gastrointestinal Bleeding: A Retrospective Study on 10 Years Experiences in Southeastern Iran.

Background: Gastrointestinal bleeding (GIB) is an emergency medical situation that is very common, although often benign but can cause considerable morbidity and mortality and health care costs. The aim of this study was to analyze the endoscopic evaluation of upper GIB (UGIB) and lower GIB (LGIB) in Sistan and Balouchestan, southeast Iran. Methods: Data from patients with GIB in a referral university-affiliated hospital in Zahedan, Southeastern Iran during a 10-year period, were obtained. A total of 21884 reports of adult patients' endoscopy and colonoscopy from 2011 to 2020 who were admitted to Ali-Ibn-Abitaleb hospital were studied of which 5862 reports were related to GIB. Incomplete files were excluded. Information on age, sex, and endoscopic diagnosis of the 5053 reports was analyzed and compared using chi-square statistical test. Results: There were 3310 men (65.6%) and 1743 women (34.4%) with a mean (±SD) of age 48.4 (±19.83) years. 3079 patients had UGIB (60.8%) and 1974 patients had LGIB (39.2%). Peptic ulcer (72.8% duodenal ulcer and 27.2% gastric ulcer) was seen as the main reason for UGIB (29.7%) and hemorrhoids were the main reason for LGIB (44.2%). Mallory-Weiss syndrome was significantly common in the age<40 years old, and the incidence rate of malignancy was significantly higher in those aged>40 years old than in the younger age group (P<0.001). Conclusion: Peptic ulcer was the most common etiological factor and it was more common in men than in women. Gastroesophageal varices were the second most common cause of UGIB. Hemorrhoids and anal fissures were observed as the most common colonoscopic findings of LGIB. The prevalences of UGIB and LGIB are more common in men than women and increase with age. It is important for physicians to constantly update their information about the spectrum of diseases in their region and their changing over time to provide accurate diagnosis and management timely.

OA08 JAK inhibitors and the risk of malignancy: a meta-analysis across licenced disease indications

Abstract Background/Aims Concerns have been raised about the risk of malignancy with Janus kinase inhibitors (JAKi) following the ORAL Surveillance study, which reported an increased incidence of malignancy with tofacitinib compared with Tumor Necrosis Factor-α inhibitors (TNFi) in people with rheumatoid arthritis (RA) aged over 50 years who had additional cardiovascular risk factors. Our objective was to estimate the risk of malignancy for all licenced JAKi across disease indications, compared with TNFi, methotrexate (MTX), and placebo. Methods A systematic search of electronic databases (Medline, EMBASE, Cochrane) was performed to identify Phase 2/3/4 RCTs and long-term extension (LTE) studies of JAKi (tofacitinib, baricitinib, upadacitinib, filgotinib, peficitinib) in adults with RA, psoriatic arthritis, psoriasis, axial spondyloarthritis, inflammatory bowel disease, or atopic dermatitis. Comparators were placebo, MTX, and TNFi. Random-effects meta-analysis was performed to compare malignancy incidence rates between JAKi and comparators. Our primary outcome measure was the incidence of all malignancies including non-melanomatous skin cancers (NMSC). Secondary outcomes were malignancies excluding NMSC, and NMSC only. Results In 62 eligible RCTs and 14 LTE studies, there were 71,767 person-years of exposure to JAKi; 2,680 to placebo; 7,827 to TNFi; and 1,074 to MTX. Comparing JAKi with placebo arms of RCTs, the incidence rate ratio (RR) for all malignancies including NMSC was not significantly different (RR 0.81; 95% CI 0.52 to 1.26; p = 0.36). Similarly, when comparing JAKi with MTX, no significant differences were observed in the incidence of malignancy (RR 0.73; 95% CI 0.33 to 1.61; p = 0.43). Compared with TNFi, however, administration of JAKi was associated with an increased incidence of malignancy (RR 1.54; 95% CI 1.19 to 2.01; p = 0.001). For all analyses, findings were consistent when excluding NMSC, when analysing NMSC only, and when including LTE data. Conclusion In trial settings, JAKi do not associate with an increased risk of malignancy compared with placebo or MTX, but are associated with an increased risk of malignancy relative to TNFi. Disclosure C. Stovin: None. M.D. Russell: Honoraria; Lilly, Galapagos, Biogen, Menarini. Other; Lilly, Pfizer, Janssen, UCB. E. Alveyn: None. O. Adeyemi: None. V. Patel: None. M.A. Adas: None. F. Atzeni: None. K.K.H. Ng: None. A.I. Rutherford: None. S. Norton: None. A.P. Cope: Consultancies; BMS, Abbvie, GSK/Galvini. Grants/research support; BMS. J.B. Galloway: Honoraria; Abbvie, Biovitrum, BMS, Celgene, Chugai, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Sobi, UCB.

Analysis of malignant neoplasms morbidity of the female genital organs and mammary glands in Chernihiv region

Malignant neoplasms of genital organs and mammary glands in women adversely affect the economic condition and demographic situation in most of the countries of the world, since a significant proportion of women affected by these diseases at working and reproductive age.The objective: to study and analyze the five-year dynamics of the incidence of for malignant neoplasms of the female genital organs and mammary glands in Chernihiv region.Materials and methods. The official data of sectoral statistical reporting for the period 2017–2021 of administrative territories of Chernihiv region and Ukraine were used. The medical statistical method and the method of structural and logical analysis were applied.Results. The analysis of the incidence for malignant neoplasms of the female genital organs and mammary glands in women in the Chernihiv region demonstrated that in the dynamics of the years 2017–2021, the incidence rate per 10 thousand female population as a whole tended to increase from 75.3 to 79.4 (in 1.05 times). At the same time, the incidence rate of malignant neoplasms of the mammary glands increased from 67.2 to 72.0 in (in 1.07 times); the frequency of cervical malignant neoplasms increased from 14.7 to 18.0 (in 1.22 times); the incidence rate of ovarian malignancies increased from 19.8 to 21.2 (1.07 times). In 2021, all the mentioned indicators in the region had higher values than in Ukraine as a whole. In the regional administrative territories these indicators had significant differences.Conclusions. High incidence rates for malignant neoplasms of the female genital organs and mammary glands in women in Chernihiv region for 2017–2021 were revealed, that requires optimization of preventive activities of the health care system at the regional level.

Computed tomography for malignancy screening in patients with rheumatoid arthritis before initiation of disease modifying antirheumatic drug.

This study aimed to clarify the usefulness of screening for malignancies using CT before the initiation of biologic and targeted synthetic DMARDs (b/tsDMARDs) in patients with active RA. We examined 2192 patients with RA who underwent plain CT scans prior to the initiation of b/tsDMARDs. The sensitivity for detecting malignancy was measured and compared with that of regular screening (physical examination and X-ray). We then evaluated the clinical characteristics, prognosis and treatment of patients with RA with concomitant malignancies. Additionally, we determined the incidence rate of malignancy in patients with RA who were initiated on b/tsDMARDs after CT screening. Of the 2192 patients, 33 (1.5%) were diagnosed with malignancy after CT screening. Whereas regular screening detected only seven malignancies, CT screening further detected 26 (including 19 at the early stage). On the other hand, 86% of the malignancies detectable by regular screening were at an advanced stage. Patients diagnosed with early-stage malignancies received RA treatments that included b/tsDMARDs after curative resection; 80% of these patients achieved low disease activity after 1 year. This rate was comparable to the patients without malignancy detection after screening (70%). The 5 year incidence of malignancy after the initiation of b/tsDMARDs after CT screening was lower than that of the RA cohort without CT screening (standardized incidence ratio: 0.35). Screening in patients with RA using CT before the initiation of b/tsDMARDs allows for the early detection and treatment of malignancy, resulting in safer and more stable b/tsDMARD treatments.

Risk of genitourinary malignancy in patients that receive anticoagulant or antiplatelet therapy.

Haematuria is a common indication for a urology evaluation. In many cases, its cause is not determined unequivocally, but it does not pose any threat to the patient. However, it can represent the first symptom of urinary tract cancer. The present study aimed to compare the risk of urological malignancies in patients with haematuria who received antiplatelet or anticoagulant therapy versus those who did not. This prospective study included 562 patients with haematuria during the period of 2018‒2021. Among these, 129 patients had macroscopic haematuria. All patients underwent a urinary tract ultrasound, CT with urography, and cystoscopy. Patients with suspected malignancy underwent an appropriate surgical procedure with a pathology examination. Data were analysed with univariate and multiple logistic regression. The incidence rates of malignancies were 21.5 % overall, and 44.2 % and 14.8 % among patients with macroscopic and microscopic haematuria, respectively. Univariate regression showed that the odds of malignancy was significantly higher among patients with antiplatelet therapy compared to patients without antiplatelet therapy (OR: 1.88, 95% CI: 1.14‒3.05). In contrast, anticoagulation therapy did not significantly increase the odds of malignancy compared to no anticoagulation therapy (OR: 1.45, 95% CI: 0.74‒2.69). However, a multiple logistic regression model that included other known risk factors (e.g., sex or age) showed similar odds of malignancy among these patient groups. Malignancy risk for patients who received anticoagulant or antiplatelet therapy was similar to the risk observed in the general population. Antiplatelet and anticoagulant therapy were not significant risk factors of urological malignancy in patients with haematuria. The results from the present study will be used in a power analysis for an upcoming multicentre study (Tab. 4, Ref. 17). Text in PDF www.elis.sk Keywords: anticoagulation therapy, antiplatelet therapy, cancer, haematuria, risk factor.

Risks of malignancies among patients with psoriasis: A cohort study of 360 patients.

Psoriasis is a systemic, chronic, immunologically-mediated disease affecting approximately 2%-4% of the worldwide population. It is well known that psoriasis is associated with several comorbidities such as metabolic syndrome, cardiovascular disease, and malignancy. Although meta-analyses and large prospective cohort studies have shown an increased risk of malignancies in patients with psoriasis worldwide, an association between psoriasis and malignancy onset has not yet been established in Japan. We retrospectively analyzed 360 patients with psoriasis at our hospital to evaluate the incidence and types of malignancies in these patients. The incidence rate of malignancy was 14.4% (52/360). Colorectal cancer was the most commonly associated malignancy (20.9%), followed by skin cancer (16.4%), gastric cancer (10.4%), and lung cancer (10.4%). The calculated age- and sex-standardized incidence ratio of malignancies was 1.235 (95% CI 0.952-1.601) which indicated that the malignancy rate was higher in patients with psoriasis than in the general population, although the difference was not statistically significant. Furthermore, the multivariate analysis revealed increased risk of malignancy in males (HR=3.15; 95% CI 1.381-7.187; p < 0.001), psoriasis onset at older age (HR=1.08; 95% CI 1.058-1.111; p < 0.01), and psoriatic erythroderma (HR=4.44; 95% CI 1.354-14.581; p < 0.05). We also observed that treatment with biological agents tends to reduce the risk of developing malignancy; however, no statistical significance was found. These results suggest that periodic screening for malignancy should be recommended in patients with psoriasis having these risk factors and in those with poorly controlled psoriatic inflammation.

JAK Inhibitor Safety Compared to Traditional Systemic Immunosuppressive Therapies.

Dermatologists treating atopic dermatitis are interested in the safety profile of the recently available JAK inhibitors, upadacitinib and abrocitinib, especially after they received boxed safety warnings. Long-term clinical trial data using these JAK inhibitors for the treatment of atopic dermatitis suggest that they are associated with very low incidence rates of malignancy, major adverse cardiac events, and thromboembolic events. However, a knowledge gap exists regarding the incidence of adverse events for JAK inhibitors compared to traditional systemic therapies used to treat poorly controlled atopic dermatitis as well as baseline rates in both atopic dermatitis and reference control populations. To address this gap, we analyzed data regarding adverse events of special interest for methotrexate, cyclosporine, and systemic corticosteroids and calculated the incidence of adverse events per 100 patient-years for these drugs. We also examined data regarding baseline incidence of adverse events in atopic dermatitis and control patients. We found that compared to upadacitinib and abrocitinib, traditional systemic therapies for atopic dermatitis demonstrated equal or higher incidence rates for malignancy (excluding non-melanoma skin cancer), non-melanoma skin cancer, major adverse cardiac events, and venous thromboembolism. Moreover, the use of upadacitinib and abrocitinib also exhibited either comparable or lower incidence of malignancy (excluding non-melanoma skin cancer), major adverse cardiac events, and venous thromboembolism, but higher rates of non-melanoma skin cancer, in comparison to baseline rates in atopic dermatitis or control patients. These findings indicate that JAK inhibitors should be positioned, at least based on safety, ahead of traditional systemic therapies for atopic dermatitis treatment.J Drugs Dermatol. 2022;21(12):1298-1303. doi:10.36849/JDD.7187.

Abstract 2772: A novel bio-physical based CDA approach for evaluating lung cancer therapeutic responses

Abstract Background: Lung cancer is the world's highest mortality and incidence rate of malignancy, and the prognosis survival rate is significantly lower than other tumors. A novel bio-physics based multi (pan)-cancer test technology named Cancer Differentiation Analysis Technology (CDA) has been developed and investigated for evaluating and monitoring lung cancer therapeutic responses. Methods: A total of 686 patients diagnosed with different sub-types of lung cancer were included in this study. CDA levels were concurrently measured in peripheral blood obtained from 686 patients during the treatment. According to the response evaluation criteria in solid tumors (RECIST) 1.1 standard, the efficacy of 686 patients after treatment was evaluated, and the diagnostic efficacy of CDA technology was evaluated by receiver operating characteristic (ROC) curve. Results: Clinical pathological parameters of the patients are listed in Table 1. The higher the CDA value, the worse the curative effect. CDA value of lung cancer in CR (complete response) group was significantly lower than that in other 3 groups (p&amp;lt;0.05). CDA value of adenocarcinoma lung cancer in CR group were significantly lower than that in SD (stable disease) group (p&amp;lt;0.05). For non - metastatic lung cancer, CDA value in CR group was significantly lower than that in SD group (p&amp;lt;0.05) The receiver ROC analysis showed that the area under curve (AUC) of lung cancer group, NSCLC group, adenocarcinoma lung cancer group, were 0.756, 0.772, and 0.792, respectively. The AUC of early lung cancer group, and non - metastatic lung cancer group were 0.794, and 0.851. Conclusions: CDA appears to have the ability to predict and monitor therapeutic responses to lung cancer surgery and chemotherapy treatments. In most cases, the CDA of CR patients is low, and there is a good correlation between CDA and curative effect in early lung cancer. CDA could be a potential candidate for evaluating lung cancer, especially for early stage lung cancer therapeutic response. Citation Format: Junjie Wu, Zixiu Zou, Xuedong Du, Yue Lin, Xing Tang, Jie Chen, Lan Peng, Chris Yu. A novel bio-physical based CDA approach for evaluating lung cancer therapeutic responses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2772.

Incidence rates for hospitalized infections, herpes zoster, and malignancies in patients with ulcerative colitis in Japan: an administrative health claims database analysis.

Patients with ulcerative colitis (UC) are at an increased risk of certain infections and malignancies compared with the general population. Incidence rates (IRs) of hospitalized infections, herpes zoster (HZ), and malignancies in patients with UC, stratified by treatment, in Japan were estimated. This retrospective study identified patients with UC treated with corticosteroids, immunosuppressants, or tumor necrosis factor inhibitors (TNFi) from 2 administrative databases (Japan Medical Data Center [JMDC] and Medical Data Vision [MDV]). IRs (unique patients with events per 100 patient-years) were estimated for hospitalized infections, HZ, and malignancies, between June 2010 and May 2018. Among 6,033 MDV patients with UC receiving corticosteroids, immunosuppressants, or TNFi, IRs (95% confidence intervals) were: hospitalized infections, 1.73 (1.52-1.93); HZ, 1.00 (0.85-1.16), and malignancies, 1.48 (1.29-1.66). Among 958 JMDC patients with UC receiving corticosteroids, immunosuppressants, or TNFi, IRs (95% confidence intervals) were: HZ, 1.82 (1.27-2.37) and malignancies, 1.35 (0.87-1.82). In both cohorts, IRs of malignancies were generally similar among patients receiving immunosuppressants, TNFi, or combination therapy (immunosuppressants and TNFi); this was also true for IRs of hospitalized infections and HZ in the MDV cohort. IRs of hospitalized infections, HZ, and malignancies were higher in patients receiving calcineurin inhibitors compared with immunosuppressants or TNFi, in both cohorts. IRs of hospitalized infections, HZ, and malignancies among patients with UC were generally similar regardless of UC treatment, except for calcineurin inhibitors.

Association between haemorrhagic fever with renal syndrome and cancers

To investigate the risk of haematologic and solid organ malignancies in patients with haemorrhagic fever with renal syndrome (HFRS) compared with the general population. This propensity-score-matched cohort study was conducted using data collected from the Korean national health insurance service (NHIS) between January 2003 and December 2017. The HFRS cohort included 5888 newly diagnosed cases of HFRS, and 412,804 general participants from the NHIS database were included as the control cohort. The incidence rate of malignancies was assessed and compared between the HFRS and control cohorts. There were 64 cases of haematologic malignancy in 236,286 person-years of observation, and 1245 cases of solid organ cancer in 209,333 person-years. The risks of haematologic malignancy and solid organ cancer were significantly higher in the HFRS cohort [adjusted hazards ratio (aHR) 4.10, 95% confidence interval (CI) 2.36-7.14] than the control cohort [aHR 2.97, 95% CI 2.60-3.38). In subgroup analysis, the HFRS cohort was associated with high hazard ratios for leukaemia and non-Hodgkin lymphoma. The HFRS cohort also had increased aHRs for all types of solid organ cancer. Patients with HFRS are at increased risk of both haematologic and solid organ malignancies compared with the general population, and this increased proportionally over time. Careful monitoring for malignancy after the onset of HFRS may be necessary.

Patient and treatment characteristics and safety outcomes of patients with relapsing-remitting multiple sclerosis treated with natalizumab in Greece: Results from the multicenter, 5-year prospective observational study 'TOPICS greece'.

BackgroundNatalizumab is a highly efficacious treatment for relapsing-remitting multiple sclerosis (RRMS).ObjectiveTo assess the real-world long-term safety of natalizumab in RRMS.MethodsThis multicenter, 5-year prospective observational study, included adults with RRMS newly initiated on natalizumab as per the approved product label in the routine care in Greece. Safety was evaluated by collecting serious adverse events (SAEs) following study enrollment.ResultsBetween 19-Apr-2012 and 18-Dec-2014, 304 eligible patients (median age at natalizumab initiation: 38.0 years; median disease duration: 6.2 years) were enrolled by 20 hospital-based neurologists. Over a median treatment duration period of 58.7 months, 50.7% of the patients discontinued natalizumab, mainly due to anti-JCV antibody detection (59.1%). The adverse event treatment discontinuation rate was 5.2%. The SAE incidence rate during the safety data collection period (median: 48.7 months) was 4.6%. The most common SAEs were infections (1.0%), including 2 cases (0.7%) of progressive multifocal leukoencephalopathy (PML), and no other opportunistic infections. PML diagnoses occurred 6.2-6.7 years after natalizumab initiation, and approximately 2 years after first detection of anti-JCV antibody for both patients. The incidence rate of malignancies was 0.7%.ConclusionIn real-world settings in Greece, natalizumab displayed an acceptable safety profile, with no new safety signals emerging.

Risk of Malignancy with Vedolizumab Versus Tumor Necrosis Factor-α Antagonists in Patients with Inflammatory Bowel Diseases.

We conducted a retrospective cohort study comparing the risk of malignancy between patients treated with vedolizumab vs. tumor necrosis factor-α (TNFα) antagonists in patients with inflammatory bowel diseases (IBD). Using an administrative claims database, we identified patients with IBD without prior malignancy who were new users of either vedolizumab or TNFα antagonists between 2014-2018, with no prior exposure to either biologic or in preceding 1y and had insurance coverage for at least 1y after treatment initiation. We estimated incidence rate of malignancy (solid organ, hematological or skin cancers) in patients treated with vedolizumab and TNFα antagonists, and compared risk using Cox proportional hazard analysis. We included 4807 patients treated with TNFα antagonists (age, 41 ± 15y, 60% with Crohn's disease [CD]) of whom 65 developed malignancy over 7214 person-year [PY] follow-up (incidence rate [IR], 9.0 per 1000-PY), and 759 patients treated with vedolizumab (age, 46 ± 16y, 42% CD) of whom 11 developed malignancy over 950-PY follow-up (IR, 11.6). No difference was observed in the incidence of malignancy between vedolizumab versus TNFα antagonists (incidence rate ratio, 1.28; 95% CI, 0.61-2.45). After adjusting for age, sex, race, comorbidity burden, disease phenotype and concomitant use of immunomodulators, no difference was observed in time to incident malignancy between vedolizumab versus TNFα antagonists (HR, 1.15; 95% CI, 0.61-2.19). Similar results were observed on stratified analysis by age and concomitant immunomodulators, and after excluding non-melanoma skin cancers. In an observational study of patients with IBD, no differences were observed in the risk of incident malignancy in patients treated with vedolizumab versus TNFα antagonists.

A Large Thyroid Fine Needle Aspiration Biopsy Cohort with Long-Term Population-Based Follow-Up.

Background: Prior studies evaluating thyroid fine needle aspiration biopsies (FNABs) have limited the calculation of risk of malignancy (ROM) to cytologic specimens with corresponding histologic specimens, and clinical follow-up for those patients who do not undergo immediate surgery has been largely disregarded. Moreover, there is marked variability in how researchers have approached thyroid FNAB statistical analyses. This study addresses the urgent need for information from a large cohort of patients with long-term clinical follow-up to more accurately determine the performance of thyroid FNAB and ROM for each diagnostic category. Methods: A retrospective review of the University of California, San Francisco (UCSF), pathology database for thyroid FNABs from January 1, 1997, to December 31, 2004, was performed. Diagnoses were coded using the 2017 The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), and patients were matched to both the UCSF cancer registry and California Cancer Registry. Data were analyzed using the Kaplan-Meier method, and stratified by TBSRTC diagnostic category. Kaplan-Meier curves were used to estimate incidence rates of malignancy, stratified by FNAB category. Cox proportional hazards models were used to determine the instantaneous ROM. Results: Initial FNABs from 2207 patients were included. Median follow-up period after the first thyroid FNAB was 13.9 years (range: 10.5-18.4 years). During follow-up, there were 279 confirmed diagnoses of thyroid malignancy. Estimates derived from Kaplan-Meier curves demonstrated that the risk of having a thyroid malignancy was low for nondiagnostic and benign categories, intermediate for atypia of undetermined significance (AUS), follicular lesion of undetermined significance (FLUS), AUS/FLUS combined, and follicular neoplasm, and high for suspicious and malignant categories. A total of 52/1575 false-negative cases (3.2%) were identified. Excluding papillary microcarcinomas, the false-negative rate was 1.5% (23/1575). No patients with a false-negative diagnosis died of thyroid cancer during the follow-up period. Conclusions: Asymptomatic patients with low-risk clinical and radiologic features and initially benign or unsatisfactory biopsy are unlikely to develop thyroid malignancy and highly unlikely to die of thyroid cancer. FNAB is highly accurate in detecting malignancy. Additional studies evaluating similar large data sets after the adoption of TBSRTC and the integration of molecular testing are needed.

Cancer incidence over the last decade in Omsk and Orenburg regions: a descriptive study

Aim. To assess the incidence of malignancies in Omsk and Orenburg Regions.Materials and Methods. We analyzed statistical reports (form # 7) from health authorities of Omsk and Orenburg Regions which contain the data on cancer incidence in the population during the last decade (2009-2018).Results. The incidence of malignancies in Omsk and Orenburg Regions had a moderate upward trend. Cancer incidence in the urban population of Orenburg region was higher than in the corresponding rural population, with the opposite ratio in the Omsk region. Average long-term standardized incidence rate of malignancies in Omsk and Orenburg regions was 276,5 0/0000 and 273,0 0/0000, respectively. Cancer incidence prevailed among the male population regardless of the indicator type. The prevalence of males across all patients was 46.0% and 46.8% in Omsk and Orenburg Region, respectively.Conclusion. Average long-term indicators of cancer incidence in Orenburg and Omsk Regions do not differ; however, different incidence pattern was detected in urban and rural populations in these regions over the decade.

OP0124 RISK OF MALIGNANCIES ACROSS BIOLOGIC CLASSES IN RHEUMATOID ARTHRITIS: ANALYSIS OF A NATIONAL CLAIM DATABASE

Background:Objectives:To estimate the incidence rate of malignancies in biologic-treated RA patients, and to compared it to the general population and across different classes of biologicsMethods:We conducted an historical cohort study within the French the national claim database, named SNDS. This database prospectively records individual health resource of 86% of the entire French population (65 million inhabitants) since 2007. RA adult patients were identified based on ICD-10 code (M05 or M06). Patients with cancer history were excluded. Treatment exposures focused on incident first use of biologics including all anti-TNF, rituximab, abatacept, tocilizumab, ustekinumab, anakinra. To identify incident treatment periods, only patients who did not receive any biologics in the 1-year period before the index date were selected. In the base case analysis, exposure was defined with a 90-day latency after treatment initiation and a 180-day carry-over period after drug discontinuation.To compare the risk of malignancies between biologic treated patients and general population, Standardized incidence ratio (SIR [95%CI]) were calculated using FRANCIM (“France Cancer Incidence et Mortalité”) estimations as reference.To compare the risk of malignancies between biologics, a propensity score (including age, sex, year of first occurrence of RA code, date of treatment initiation, number of previous DMARDs, Charlson comorbidity index, diagnosis of tobacco and/or alcohol-associated disorders, number of hospitalizations for RA, cumulative corticosteroid dose) was calculated for each comparison. Hazard Ratios (HRs) for risk of cancer were estimated using Cox proportional hazard model using inverse probability of treatment weighting (IPTW) with propensity score. Exposure was considered as a time-dependent variable and propensity scores were estimated dynamically using pooled logistic regression reassessed for each new exposure.Results:Between 2007 and 2016, 31,792 patients (112,802 patient-years)- were exposed to biologics. The annual incidence rate of overall malignancies was 0.865 per 100 patients-years. Malignancies occurred in 730 patients exposed to anti-TNF, 235 patients exposed to another biologic and 11 exposed to both.As compared to the general population, biologic treated patients had an increased risk of lung cancer (SIR=1.35 [1.14;1.60]), a decreased risk of pancreatic cancer (SIR=0.52[0.31-0.85]) and no significant increased risk of invasive melanoma (SIR=1.15 [0.82;1.61]). Results were similar for anti-TNF-treated patients. Other biologics were not analyzed separately due to small sample sizes.The overall risk of malignancies and risk of lymphoma did not differ between anti-TNF and other biologics (analysed all together), or abatacept. Within the anti-TNF class, the overall risk of malignancies and risk of lymphoma did not differ between etanercept and monoclonal anti-TNF (table).Type of malignanciesHR [95% CI]p-valueHR [95% CI]p-valueHR [95% CI]p-valueAnti-TNF (ref) vs. other biologicsAnti-TNF (ref) vs. AbataceptMonoclonal anti-TNF (ref) vs. EtanerceptP-Y exposure83256 vs. 2564991770 vs. 468149620 vs. 36790All malignancies (excl. non-melanoma skin cancer)0.97 [0.81;1.17]p=0.71.27 [0.89;1.81]p=0.21.11 [0.94;1.32]p=0.2Solid cancer (excl. non-melanoma skin cancer)0.98 [0.80;1.20]p=0.81.23 [0.84;1.82]p=0.41.10 [0.92;1.32]p=0.3Lymphoma0.69 [0.32;1.46]p=0.31.73 [0.55;5.48]p=0.50.87 [0.49;1.57]p=0.7Conclusion:Using a large nationwide healthcare database, representative of the French population, the overall risk of malignancies did not seem to differ across the different classes of biologic. Among anti-TNF, the risk of malignancies of lymphoma did not differ between etanercept and monoclonal antibodies. The risk of organ specific cancers, except lung cancer, did not differ from that of general population.Disclosure of Interests:Raphaèle Seror Consultant of: BMS, Medimmune, Novartis, Pfizer, GSK, Lilly, Bruno Fautrel Grant/research support from: AbbVie, Lilly, MSD, Pfizer, Consultant of: AbbVie, Biogen, BMS, Boehringer Ingelheim, Celgene, Lilly, Janssen, Medac MSD France, Nordic Pharma, Novartis, Pfizer, Roche, Sanofi Aventis, SOBI and UCB, Alexandre Lafourcade: None declared, yann de-rycke: None declared, Xavier Mariette Consultant of: BMS, Gilead, Medimmune, Novartis, Pfizer, Servier, UCB, Florence Tubach Grant/research support from: Florence TUBACH is head of the Centre de Pharmacoépidémiologie (Cephepi) of the Assistance Publique – Hôpitaux de Paris and of the Clinical Research Unit of Pitié-Salpêtrière hospital, both these structures have received research funding, grants and fees for consultant activities from a large number of pharmaceutical companies, that have contributed indiscriminately to the salaries of its employees. Florence Tubach didn’t receive any personal remuneration from these companies.