First-Line Pharmacotherapies and Survival among Patients Diagnosed with Non-Resectable NSCLC: A Real-Life Setting Study with Gender Prospective

(1) Purpose: To describe first-line pharmacotherapy and overall survival in non-resectable non-small cell lung cancer (nrNSCLC) patients by gender. (2) Methods: Incident cases of nrNSCLC recorded between 2009 and 2019 (cohort entry) in the pathology registry of the regional administrative healthcare database of Tuscany were identified. Records of antineoplastic therapies delivered up to 4 months following cohort entry were classified as chemotherapy, target therapies, immunotherapies, and undefined monoclonal antibodies. First-line treatment and survival of patients receiving drug treatment was described. Analyses were stratified according to histology, gender, and cohort entry year. (3) Results: 4393 incident cases of nrNSCLC were included. Women with non-squamous-NSCLC received target-therapy more frequently than men (14.9% vs. 6.5%). Immunotherapy incidence of use varied between 3.8% (2017) and 9.1% (2019). The 2-year survival rate increased over time: for non-squamous-NSCLC, it was 22.3% (2009–2011) and 30.6% (2018–2019), while for squamous-NSCLC, it was 13.5% and 22.5%, respectively. After multivariate analysis, a low reduction in mortality risk in 2018–2019 vs. 2009–2011 was found (non-squamous: HR: 0.95 CI95%: 0.92–0.98; squamous: HR: 0.94 CI95%: 0.90–0.98). Among non-squamous NSCLC, median survival was longer in women than in men (389 vs. 276 days). (4) Conclusion: In light of sex-related biomolecular differences, among non-squamous NSCLC, women received target-therapy more frequently than men. Survival seemed to slightly improve over the study period for both histologies, despite a poor reduction in mortality risk was still observed.

Identification of Tobacco-Related Cancer Diagnoses among Individuals with Psychiatric Disorders: A Population-Based Matched Cohort Study Using a Competing Risks Approach from British Columbia

Background: Individuals with psychiatric disorders (PD) have a high prevalence of tobacco use. Therefore, we assessed the hazard of receiving a tobacco-related (TR) cancer diagnosis among individuals with PD. Methods: Several population-based provincial databases were used to identify individuals in BC diagnosed with depression, schizophrenia, bipolar disorder, anxiety disorders, or multiple PD between 1990 and 2013. A primary population proxy comparison group (appendicitis) was also identified and matched to the psychiatric cohort based on age at cohort entry, gender, year of cohort entry, and postal code. We linked individuals in the cohort and comparison groups with the BC Cancer Registry. Using a competing risks approach, we estimated the effect of having a PD on the risk of receiving a TR cancer diagnosis, in light of the competing risk of mortality. Results: In total, 165,289 patients were included. Individuals with depression (HR = 0.81; p < 0.01; 95% CI: 0.73–0.91), anxiety disorders (HR = 0.84; p = 0.02; 95% CI: 0.73–0.97), or multiple PD (HR = 0.74; p < 0.01; 95% CI: 0.66–0.83) had a statistically significant lower risk of a TR cancer diagnosis compared to the comparison group. Individuals with schizophrenia (HR = 0.86; p = 0.40; 95% CI: 0.62–1.21) or bipolar disorder (HR = 0.58; p = 0.12; 95% CI: 0.29–1.14), however, showed no evidence of a statistically significant difference from the comparison group. Interpretation: We found that individuals with depression, anxiety disorders, or multiple PD diagnoses had a significantly reduced risk of receiving a tobacco-related cancer diagnosis. These results were unexpected and could be explained by individuals with a PD having barriers to a cancer diagnosis rather than a true decreased incidence.

Immortal time bias for life-long conditions in retrospective observational studies using electronic health records

Background Immortal time bias is common in observational studies but is typically described for pharmacoepidemiology studies where there is a delay between cohort entry and treatment initiation. Methods This study used the Clinical Practice Research Datalink (CPRD) and linked national mortality data in England from 2000–2019 to investigate immortal time bias for a specific life-long condition, intellectual disability. Life expectancy (Chiang’s abridged life table approach) was compared for 33,867 exposed and 980,586 unexposed individuals aged 10+ years using five methods: (1) treating immortal time as observation time; (2) excluding time before date of first exposure diagnosis; (3) matching cohort entry to first exposure diagnosis; (4) excluding time before proxy date of entering first exposure diagnosis (by the physician); and (5) treating exposure as a time-dependent measure. Results When not considered in the design or analysis (Method 1), immortal time bias led to disproportionately high life expectancy for the exposed population during earlier calendar periods (additional years expected to live: 2000–2004: 65.6 [95% CI: 63.6,67.6]; 2005–2009: 59.9 [58.8,60.9]; 2010–2014: 58.0 [57.1,58.9]; 2015–2019: 58.2 [56.8,59.7]). Date of entry of diagnosis (Method 4) was unreliable in this CPRD cohort. The final methods (Method 2, 3 and 5) appeared to solve the main theoretical problem but residual bias may have remained. Conclusions We conclude that immortal time bias is a significant issue for studies of life-long conditions that use electronic health record data and requires careful consideration of how clinical diagnoses are entered onto electronic health record systems.

313Long-acting bronchodilators and risk of acute coronary syndrome

Background There is concern that long-acting bronchodilators (long-acting muscarinic antagonists [LAMAs]) and long-acting beta2-agonists [LABAs]) may further increase the already elevated risk of cardiovascular events in patients with chronic obstructive pulmonary disease (COPD). Guidelines recommend stepwise escalation from one to two long-acting bronchodilators in patients with uncontrolled symptoms, but information about the impact of this treatment intensification on acute coronary syndrome (ACS) risk is limited. Methods We undertook a nested case-control study using national administrative data to estimate the risk of ACS in users of dual LAMA and LABA therapy, and users of LABA monotherapy, relative to users of LAMA monotherapy. The underlying study cohort comprised patients aged &gt;45 years who initiated long-acting bronchodilator therapy for COPD between 2006 and 2013 (n = 83,417). Cases were patients diagnosed with fatal or non-fatal ACS after cohort entry (n = 5,399). Up to 10 controls per case, matched by age, sex, date of cohort entry, and COPD severity, were randomly selected from the study cohort using risk set sampling. Odd ratios and 95% confidence intervals were estimated using conditional logistic regression. Results Relative to current use of LAMA monotherapy, the adjusted odds ratios for current use of dual LAMA and LABA therapy, and of LABA monotherapy, were 1.28 (95% CI 1.13–1.44) and 1.0 (95% CI 0.91–1.10), respectively. Conclusions Use of two long-acting bronchodilators rather than LAMA monotherapy, is associated with a higher risk of ACS, while the risks associated with LAMA and LABA monotherapy are comparable. Key messages The clinical benefit of adding a second long-acting bronchodilator to LAMA or LABA monotherapy is modest and, at the same time, is associated with an increased risk of ACS in a patient group already at high risk.

The association between statin and COVID-19 adverse outcomes: National COVID-19 cohort in South Korea

Background: There currently exists limited and conflicting clinical data on the use of statins amongst COVID-19 patients. Given the both paucity and lack of consensus among data on statin's efficacy and safety amongst COVID-19 patients, the current guideline is to continue statin in COVID-19 patients, who have previously been treated with statins. The aim of this paper was to compare hospitalized patients with COVID-19 who did and did not receive statins, in terms of COVID-19 outcomes. Methods: We conducted population-based retrospective study using South Korea's nationwide healthcare database as of May 15 2020. We identified 4,349 patients hospitalized with COVID-19 and aged 40 years or older. The cohort entry was defined as the date of hospitalization. Statin users were individuals with inpatient and outpatient prescription records of statins in the 240 days before cohort entry, and non-users were those without such records during this period. Our primary outcome was a composite endpoint of all-cause death, intensive care unit (ICU) admission, mechanical ventilation use and cardiovascular outcomes (myocardial infarction (MI), transient cerebral ischemic attacks (TIA) or stroke). We conducted inverse probability of treatment weighting (IPTW)-adjusted logistic regression analysis to estimate odds ratio (OR) and corresponding 95% confidence intervals (CI), to compare outcomes between statin users and non-users. Findings: 1,115 patients were statin users (mean age = 65.9 years; 60% female), and 3,234 were non-users (mean age = 58.3 years; 64% female). Statin use was not associated with increased risk of the primary outcome (IPTW OR 0.82; 95% CI: 0.60-1.11). Subgroup analysis showed a protective role of statins, for individuals with hypertension (IPTW OR 0.40; 95% CI: 0.23-0.69, p for interaction: 0.0087). Interpretation: Given that statins are not detrimental and that it may be beneficial amongst hypertensive patients and relatively cheap, we would encourage further investigation into statin for the prevention and treatment of COVID-19.

The Cumulative Dose-Dependent Effects of Metformin on the Development of Tuberculosis in Patients Newly Diagnosed with Type 2 Diabetes Mellitus

Background: Diabetes mellitus (DM) is a well-known risk factor for tuberculosis (TB). Metformin, which is an essential anti-diabetic drug, has been shown to exhibit anti-TB effects in patients with DM. Its effect on preventing the development of TB among patients who are newly diagnosed with DM remains unclear. We evaluated the protective effect of metformin on the development of TB among newly diagnosed patients with type 2 DM.Methods: This was a retrospective cohort study using the claims database. The study population included newly diagnosed type 2 DM patients between January 2003 and March 2011. A metformin user was defined if a patient had taken metformin for more than 28 days within the first 6 months after the initial cohort entry. Primary outcome was the development of TB within 2 years after the index date. Results: Metformin use was not associated with the prevention of TB development (Metformin user: 44/12,916 (0.34%) vs. Metformin non-user: 40/12,916(0.31%); HR, 1.17; 95% CI, 0.75-1.83; P = 0.482). There was, however, a reduction in the development of TB among patients taking a higher cumulative dose of metformin. Patients in the highest quartile of cumulative metformin dose had only a 10% risk of developing TB compared to metformin non-users. In contrast, patients in the second quartile had a higher risk of developing TB than patients in the first quartile. Conclusions: The highest cumulative doses of metformin were protective against the development of TB among newly diagnosed type 2 DM patients.

Factors associated with neuropsychiatric involvement in Latin American patients with systemic lupus erythematosus

Introduction Factors related to presentation of neuropsychiatric (NP) SLE manifestations, early in the course of the disease, and during follow up have not been clearly established. Purpose To identify disease and non-disease related factors associated with NP manifestations in early SLE. Methods We included 1193 patients from the GLADEL inception cohort free of NP involvement at cohort entry. We evaluated the association of demographic, clinical and laboratory data with NP involvement during follow-up. Statistical methods Independent factors associated with NP involvement were identified using a multivariable Cox regression model. Results Factors independently associated with NP manifestations were: mestizo ethnicity (HR 1.701, 95% CI 1.282–2.258, p = 0.0002), myalgias/myositis (HR 1.832, 95% CI 1.335–2.515, p = 0.0002), pneumonitis (HR 2.476, 95% CI 1.085–5.648, p = 0.0312), shrinking lung (HR 2.428, 95% CI 1.074–5.493, p = 0.0331) and hemolytic anemia (HR 1.629, 95% CI 1.130–2.347, p = 0.0089). Longer disease duration at cohort entry (13 to 24 months) was associated with a lower risk of developing NP manifestations (HR 0.642, 95% CI 0.441–0.934, p = 0.0206). Conclusions Patients with myalgias/myositis, pneumonitis, shrinking lung and hemolytic anemia are at higher risk of NP involvement, whereas longer disease duration at cohort entry is associated with a lower risk of developing NP involvement.

POS0122 THE ASSOCIATIONS BETWEEN DISEASE MODIFYING ANTI-RHEUMATIC DRUGS AND INCIDENT, AND PROGRESSION OF, RADIOGRAPHIC HAND OSTEOARTHRITIS IN RHEUMATOID ARTHRITIS PATIENTS

Background:Hand osteoarthritis (OA) is characterized by bone erosions, joint space remodeling, and new bone formation mainly in distal interphalangeal (DIP) joints and thereby differs from hand manifestations in rheumatoid arthritis (RA). There are conflicting data about the benefit of treatment with conventional synthetic (cs) and biologic (b) disease modifying anti-rheumatic treatment (DMARD) on DIP OA.Objectives:To assess the associations between DMARDs and incident, and progression of, radiographic DIP OA in RA patients.Methods:We performed two observational cohort studies in the longitudinal Swiss Clinical Quality Management in Rheumatic Diseases registry (SCQM) between 1997 and 2014. RA patients who had ≥2 eligible hand radiographs were included at their first eligible radiograph (baseline) and were followed until the outcome or their last eligible radiograph. Radiographs were eligible if all 8 DIP joints could be scored. Modified Kellgren-Lawrence scores (KLS) were obtained by evaluating DIP joints for severity of osteophytes, joint space narrowing, subchondral sclerosis, and erosions. Incident/existing DIP OA was defined as KLS ≥2 in ≥1 DIP joint. Progression of existing DIP OA was defined as an increase of ≥1 in KLS in ≥1 DIP joint. We divided the study population into two cohorts based on whether DIP OA was present or absent at cohort entry (cohorts 1 and 2, respectively). Exposure status was defined time-dependently into mutually exclusive exposure groups: csDMARD monotherapy, bDMARD monotherapy, bDMARD/csDMARD combination therapy, past bDMARD/csDMARD therapy, or never DMARD use. Cox time-varying proportional hazard regression analyses were used to estimate hazard ratios (HRs) with 95% confidence intervals (CI) of DIP OA progression (cohort 1) or DIP OA incidence (cohort 2) associated with DMARD exposure categories (csDMARD monotherapy was the reference group because it was the largest group). Exposure and covariate information were extracted at every radiograph and other visit date. Missing covariate information was imputed using multiple imputation by chained equations. In sensitivity analyses, we repeated all analyses using generalised estimation equations (GEE).Results:Among 2234 RA patients with 5928 eligible radiographs, 1340 patients had radiographic DIP OA at cohort entry (cohort 1) and 894 were DIP OA naïve (cohort 2). In cohort 1, radiographic progression of existing DIP OA was characterized by new osteophyte formation (666, 52.4%), followed by joint space narrowing (379, 27.5%), subchondral sclerosis (238, 17.8%), and erosion (62, 4.3%). bDMARD monotherapy was associated with an increased risk of radiographic DIP OA progression compared to csDMARD monotherapy (adjusted HR 1.34, 95% CI 1.07–1.69). The risk of DIP OA progression was not significant in csDMARD/bDMARD combination therapy users (adjusted HR 1.12, 95% CI 0.96–1.31), absent in past DMARD users (adjusted HR 0.96, 95% CI 0.66–1.41), and significantly lower among never DMARD users (adjusted HR 0.54, 95% CI 0.33–0.90), compared to csDMARD monotherapy users. In cohort 2, the risk of incident OA did not differ materially between treatment groups. Results from GEE analyses corroborated all findings.Conclusion:Our results from this real-world RA cohort suggest that monotherapy with bDMARDs is not associated with incident DIP OA but may increase the risk of radiographic progression of existing DIP OA when compared to csDMARDs.Acknowledgements:We thank all patients and rheumatologists involved for their contribution to the SCQM RA cohort. A list of rheumatology offices and hospitals that contribute to the SCQM registry can be found at http://www.scqm.ch/institutions. The SCQM is financially supported by pharmaceutical industries and donors. A list of financial supporters can be found at http://www.scqm.ch/sponsors.Disclosure of Interests:Theresa Burkard: None declared, Christian Lechtenboehmer: None declared, Stephan Reichenbach: None declared, Monika Hebeisen: None declared, Ulrich Walker: None declared, Andrea Michelle Burden: None declared, Thomas Hügle Consultant of: Pfizer, Abbvie, Novartis, Grant/research support from: GSK, Jansen, Pfizer, Abbvie, Novartis, Roche, MSD, Sanofi, BMS, Eli Lilly, UCB

AB0206 DESCRIPTION AND FOLLOW-UP OF RHEUMATOID ARTHRITIS PATIENTS WHO STOPPED B/TSDMARD THERAPY, STRATIFIED BY CESSATION REASON

Background:Biologic or targeted synthetic disease modifying antirheumatic drugs (b/tsDMARD) may be stopped for several reasons such as non-response, adverse events, remission, or other reasons (e.g. major surgery). Understanding the reasons and consequences of b/tsDMARD therapy cessation may contribute towards therapy decision guidance. Moreover, identifying patient characteristics leading to the re-start of b/tsDMARD therapy may guide decision-making as to which patients should remain on continuous b/tsDMARD therapy versus who may potentially stop b/tsDMARD therapy.Objectives:To describe and follow rheumatoid arthritis (RA) patients who stopped b/tsDMARD therapy, stratified by cessation reason.Methods:We conducted a descriptive cohort study among adult RA patients in the longitudinal Swiss Clinical Quality Management in Rheumatic Diseases (SCQM) between 1997 and 2019. RA patients who stopped their first b/tsDMARD therapy were eligible, with therapy stop date defining cohort entry. We followed all eligible patients from cohort entry until b/tsDMARD re-start (the outcome) or censoring due to end of patient record. All analyses were carried out stratified by cessation reason (non-response, adverse events, remission, other reasons, unknown reasons). We described patient characteristics (demographics, lifestyle factors, clinical information, other medication use, relevant comorbidities) at cohort entry. Furthermore, we estimated Kaplan Meier curves to describe differences in cumulative incidences of b/tsDMARD re-start. Finally, we assessed patient characteristics at b/tsDMARD re-start and compared them with those at cohort entry.Results:Among 2559 eligible RA patients, the majority stopped their b/tsDMARD due to non-response (982, 38%), followed by adverse events (475, 19%), other reasons (445, 17%), unknown reasons (444, 17%), and remission (213, 8%). Mean age at b/tsDMARD stop was around 56.2 years except in patients who stopped due to remission (mean age of 58.1 years). The majority of patients were women (78%), stopping due to an adverse event had the highest proportion of women (84%), stopping due to remission had the lowest proportion of women (70%). Compared to patients who stopped b/tsDMARD therapy due to non-response or adverse events, patients who stopped due to remission were generally more physically active, better educated, less likely to have a family history of rheumatic diseases, and had shorter median disease duration. A total of 2086 patients (82%) re-started b/tsDMARD therapy during follow-up. Of these, the majority did so after stopping due to non-response (94%), followed by adverse events (82%), unknown reasons (79%), other reasons (74%), and remission (47%). The median cumulative incidence of re-starting b/tsDMARD therapy was shortest after non-response (30 days), followed by unknown reasons (31 days), adverse events (94 days), other reasons (212 days), and remission (1597 days). The population who stopped b/tsDMARD therapy due to remission or other reasons yielded increased RA disease activity and an increase in proportions of women, cardiac diseases, degenerative joint disease, other auto-immune diseases, and of patients with family history of rheumatic diseases at the date of b/tsDMARD re-start. However, among patients who stopped b/tsDMARD therapy due to non-response or adverse events, patient characteristics at b/tsDMARD re-start were unchanged compared to those at b/tsDMARD stop.Conclusion:Observed differences in patient characteristics at b/tsDMARD stop may yield insight into why the patient was not responding, had an adverse event, or achieved remission. Observed changes in patient characteristics from the date of b/tsDMARD stop to re-start identified which ones may lead to a worsening of RA activity in the absence of b/tsDMARD therapy.Acknowledgements:We would like to thank Dr. Almut Scherer, Monika Hebeisen, and Eleftherios Papagiannoulis from SCQM for providing the data and answering questions thereto. A list of rheumatology offices and hospitals that are contributing to the SCQM registries can be found on www.scqm.ch/institutions. The SCQM is financially supported by pharmaceutical industries and donors. A list of financial supporters can be found on www.scqm.ch/sponsors.Disclosure of Interests:Theresa Burkard: None declared, Enriqueta Vallejo-Yagüe: None declared, Thomas Hügle Consultant of: Pfizer, Abbvie, Novartis, Grant/research support from: GSK, Jansen, Pfizer, Abbvie, Novartis, Roche, MSD, Sanofi, BMS, Eli Lilly, UCB, Axel Finckh Speakers bureau: Pfizer, Eli-Lilly, Paid instructor for: Pfizer, Eli-Lilly, Consultant of: Pfizer, BMS, Novartis, Grant/research support from: AbbVie, AB2Bio, BMS, Gilead, Pfizer, Viatris, Andrea Michelle Burden: None declared

497 Clinical Presentation Prior to Idiopathic Hypersomnia Diagnosis Among US Adults: A Retrospective, Real-World Claims Analysis

Introduction Idiopathic hypersomnia (IH) is a rare, serious central hypersomnolence disorder for which there are no FDA-approved medications available. A retrospective study was conducted to characterize newly diagnosed patients with IH in the United States. Here, we report morbidity and comorbidity claims prior to IH diagnosis. Methods Claims from the IBM® MarketScan® database were analyzed between January 2014 and September 2019. The general population cohort included all adults with ≥12 months of continuous enrollment. From this population, a cohort with newly diagnosed IH was identified, defined as ≥2 claims with an IH diagnosis code ≥1 day and ≤180 days apart, and without an IH diagnosis in the 12 months prior to cohort entry. Patients without continuous medical/prescription coverage (enrollment gaps &gt;30 days) in the 12 months prior to cohort entry were excluded. Claims with diagnoses for select morbid/comorbid conditions were identified from 12 months prior to cohort entry for the IH and general population cohorts and summarized using descriptive statistics. A sensitivity analysis was conducted on IH patients with the diagnosis code recorded in the primary position (“primary IH”) on the claims to understand the effects of applying a more specific definition of IH. Results Of the general population cohort (N=32,948,986; mean age, 42 years; 52% female), 4,980 (0.015%) newly diagnosed IH patients were identified (mean age, 43 years; 67% female). Sleep-related morbidities in the 12 months prior to cohort entry included narcolepsy type 2 (17%/0.1%) and hypersomnia (10%/0.2%) for the IH/general population cohorts, respectively. Common comorbidities were sleep apnea (50%/4%), mood disorders (32%/8%), depressive disorders (31%/7%), anxiety disorders (31%/9%), hyperlipidemia (30%/20%), headache/migraine (24%/7%), diabetes or use of diabetes/obesity medication (20%/12%), hypertension (15%/10%), and cardiovascular disease (14%/8%) for the IH/general population cohorts, respectively. Common morbidities/comorbidities for the primary IH cohort (n=2,205) were generally similar to the overall IH population. Conclusion Compared with the general MarketScan® population, morbidities/comorbidities were more common for IH patients across all conditions analyzed, including sleep disorders and psychiatric, cardiometabolic, and cardiovascular disease. With cardiovascular risk factors common upon diagnosis of IH, therapies that do not increase cardiovascular risk are warranted. Support (if any) Jazz Pharmaceuticals