Search

Objective Most patients with rheumatoid arthritis (RA) strive to consolidate their treatment from methotrexate combinations. The objective of this analysis was to identify patients with RA most likely to achieve remission with tocilizumab (TCZ) monotherapy by developing and validating a prediction model and associated remission score. Methods We identified four TCZ monotherapy randomized controlled trials in RA and chose two for derivation and two for internal validation. Remission was defined as a Clinical Disease Activity Index score less than 2.8 at 24 weeks post randomization. We used logistic regression to assess the association between each predictor and remission. After selecting variables and assessing model performance in the derivation data set, we assessed model performance in the validation data set. The cohorts were combined to calculate a remission prediction score. Results The variables selected included younger age, male sex, lower baseline Clinical Disease Activity Index score, shorter RA disease duration, region of the world (Europe and South America [increased odds of remission] versus Asia and North America), no previous exposure to disease-modifying antirheumatic drugs and/or methotrexate, lower baseline Health Assessment Questionnaire Disability Index score, and baseline hematocrit. The area under the receiver operating characteristic curve was 0.739 in the derivation data set and 0.756 in the validation data set. Patients were categorized into three remission prediction categories based on the remission prediction score: 40% in the low (less than 10% probability of remission), 45% in the intermediate (10%-25% probability), and 15% in the moderate remission prediction category (greater than 25% probability). Conclusion We used easily accessible factors to develop a remission prediction score to predict RA remission at 24 weeks after initializing TCZ monotherapy. These results may provide guidance to clinicians tailoring treatment options based on clinical characteristics.

Introduction Real-world use of immunomodulating therapy (IMT) in patients with systemic sclerosis (SSc) was investigated for the first time in a descriptive, retrospective cohort analysis of claims made in a healthcare insurance database to characterize treatment patterns and their alignment with SSc disease manifestations. Methods Treatment patterns and disease manifestations, symptoms, complications, and comorbidities were assessed in patients with SSc enrolled in a US healthcare claims database who received treatment between January 2006 and December 2013 and for whom data were available 6 months before and 12 months after SSc diagnosis. Results Among 7812 eligible patients, 6852 received treatments of interest for SSc and 2404 (30.8%) received IMT during the first year after SSc diagnosis. In the first year after diagnosis, the most common claims were for antibiotics (61.7%), opioids (50.6%), glucocorticoids (46.5%), and proton pump inhibitors (35.4%); the most common organs involved with complications among patients with SSc were lung (30.5%), heart (17.4%), and gastrointestinal tract (22.4%); the most common signs or symptoms were musculoskeletal (16.1%) and fatigue (10.5%); 1035 patients (15.1%) had infections and 14 (0.2%) had malignancies. Among patients who received IMT, 43.8% received at least hydroxychloroquine and 21.1% received at least methotrexate; 460 patients switched to a second IMT, 23.0% to at least methotrexate and 22.8% to at least mycophenolate mofetil. The most common comorbidities reported with first IMT were in lung (11.8%), overlap syndrome (8.4%), heart (5.3%), and gastrointestinal (6.8%) categories. Conclusion One-third of patients with SSc in the healthcare claims population received IMTs during the first year after diagnosis. However, patients who received IMTs had disease manifestations similar to those of the overall SSc healthcare claims population. Electronic Supplementary Material The online version of this article (10.1007/s40744-019-00181-8) contains supplementary material, which is available to authorized users.

Objectives To examine the rate of incident malignancies excluding non-melanoma skin cancer (NMSC) in patients with rheumatoid arthritis (RA) newly treated with tocilizumab versus other biologic drugs. Methods We conducted a cohort study using data from 3 U.S. insurance claims databases – Medicare (2010–2015), ‘IMS’ PharMetrics Plus (2011–2015) and Truven ‘MarketScan’ (2011–2015). Adults with RA who newly started tocilizumab or a TNF inhibitor (TNFi) after failing a different TNFi, abatacept or tofacitinib were included. The primary outcome was development of any malignancies excluding NMSC. For confounding control, tocilizumab starters were propensity score (PS)-matched to TNFi starters with a variable ratio of 1:3 within each database. Hazard ratios (HR) from the 3 PS-matched cohorts were combined by an inverse variance-weighted, fixed-effects model. We conducted a secondary analysis where we compared tocilizumab initiators with abatacept initiators. Results We included 13,102 tocilizumab initiators PS-matched to 26,727 TNFi initiators in all three databases. The incidence rate of malignancies per 1,000 person-years ranged from 8.27 (IMS) to 23.18 (Medicare) in the tocilizumab group and from 9.64 (MarketScan) to 21.46 (Medicare) in the TNFi group. The risk of incident malignancies was similar between tocilizumab and TNFi initiators across all three databases, with a combined HR of 0.98 (95%CI 0.80–1.19) in tocilizumab versus TNFi. The secondary analysis comparing tocilizumab versus abatacept showed similar results (combined HR 0.97, 95%CI 0.74–1.27). Conclusions This large multi-database cohort study found no difference in the risk of malignancies excluding NMSC in RA patients who newly started tocilizumab compared with TNFi or abatacept.

Introduction The safety profile of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) is well established. TCZ was approved to treat giant cell arteritis (GCA) in 2017 in the USA and Europe, and its safety profile in patients with GCA continues to be defined. The objective of this analysis was to examine incidence rates (IRs) of adverse events of special interest (AESI) occurring during the TCZ clinical development program and in healthcare claims data in patients with GCA or RA. Methods TCZ-naïve patients with GCA or RA were identified in the MarketScan administrative healthcare claims database. TCZ-treated patients with GCA from the GiACTA trial and TCZ-treated patients with RA from pooled clinical trial data were analyzed. The IRs of AESI (AESI IRs) were calculated for all cohorts. In the claims cohorts, risks of AESI were estimated using Poisson regression. Results TCZ-naïve claims cohorts comprised 4804 patients with GCA [mean (standard deviation) age 73.4 (9.8) years; follow-up 3.9 (3.1) years] and 15,164 patients with RA [age 60.3 (8.2) years; follow-up, 4.5 (2.8) years]. TCZ-treated clinical trial cohorts comprised 149 patients with GCA [age 69.5 (8.4) years; exposure approx. 138 patient-years (PY)] and 7647 with RA [age 52 (12.6) years; exposure approx. 22,394 PY]. The IRs of infections, stroke, malignancies, myocardial infarction, and gastrointestinal perforations in the GCA claims cohort exceeded those in the RA claims cohort; the risk of AESI (adjusted for age and glucocorticoid use) was higher in patients with GCA than in those with RA. Similar patterns to the claims cohorts in terms of the AESI IRs were observed in clinical trial cohorts, although the number of events was limited in the GCA trial cohort. Conclusion Higher IRs of AESI were observed in patients with GCA versus those with RA in both TCZ-naïve and -treated cohorts. Differences in underlying disease, age, and glucocorticoid use may influence AESI incidence, irrespective of intervention. Funding This study was funded by F. Hoffmann-La Roche Ltd and Genentech, Inc. Article processing charges were funded by F. Hoffmann-La Roche Ltd. Plain Language Summary Plain language summary is available for this article.

Objectives While tocilizumab may increase serum lipid levels, recent studies do not suggest a link between tocilizumab use and clinical cardiovascular risk in patients with rheumatoid arthritis (RA). Methods To compare cardiovascular safety of tocilizumab with abatacept, we conducted a cohort study using data from Medicare (2010–2013), IMS PharMetrics (2011–2014) and MarketScan (2011-6/2015). RA patients aged ≥18 years who newly started tocilizumab or abatacept entered the cohort on the day of their first use of tocilizumab or abatacept after a continuous enrollment period for ≥365 days. The primary outcome was a composite cardiovascular endpoint of hospitalization for myocardial infarction or stroke. To control for more than 60 confounders, tocilizumab starters were propensity score (PS)-matched to abatacept starters with a variable ratio of 1:3 within each database. A fixed-effects model combined database-specific hazard ratios (HR). Results We included 6237 tocilizumab starters PS-matched to 14,685 abatacept starters in all three databases. Mean age was 72 years in Medicare, 51 in PharMetrics and 53 in MarketScan. The incidence rate of the composite cardiovascular events per 100 person-years ranged from 0.37 (PharMetrics) to 1.64 (Medicare) in the tocilizumab group and from 0.59 (PharMetrics) to 1.69 (Medicare) in the abatacept group. The risk of the composite cardiovascular events was similar between the two groups across all three databases, with a combined HR of 0.82 (95% CI: 0.55–1.22) in tocilizumab versus abatacept starters. Conclusions This multi-database cohort study found no difference in the risk of cardiovascular events in RA patients who newly started tocilizumab versus abatacept.

Background Flight attendants are an understudied occupational group, despite undergoing a wide and unique range of adverse job-related exposures. In our study, we aimed to characterize the health profile of cabin crew relative to the U.S. general population. Methods In 2014–2015, we surveyed participants of the Harvard Flight Attendant Health Study. We compared the prevalence of their health conditions to a contemporaneous cohort in the National Health and Nutrition Examination Survey (NHANES 2013–2014) using age-weighted standardized prevalence ratios (SPRs). We also analyzed associations between job tenure and selected health outcomes, using logistic regression and adjusting for potential confounders. Results Compared to the NHANES population (n = 2729), flight attendants (n = 5366) had a higher prevalence of female reproductive cancers (SPR = 1.66, 95% CI: 1.18–2.33), cancers at all sites (SPR = 2.15, 95% CI: 1.73–2.67 among females), as well as sleep disorders, fatigue, and depression, with SPRs ranging between 1.98 and 5.57 depending on gender and the specific condition examined. In contrast, we observed a decreased prevalence of cardiac and respiratory outcomes among flight crew relative to NHANES. Health conditions that increased with longer job tenure were sleep disorders, anxiety/depression, alcohol abuse, any cancer, peripheral artery disease, sinusitis, foot surgery, infertility, and several perinatal outcomes. Conclusions We observed higher rates of specific adverse health outcomes in U.S. flight attendants compared to the general population, as well as associations between longer tenure and health conditions, which should be interpreted in light of recall bias and a cross-sectional design. Future longitudinal studies should evaluate specific exposure-disease associations among flight crew. Electronic supplementary material The online version of this article (10.1186/s12889-018-5221-3) contains supplementary material, which is available to authorized users.

Community-level approaches for pediatric asthma management rely on locally collected information derived primarily from two sources: claims records and school-based surveys. We combined claims and school-based surveillance data, and examined the asthma-related risk patterns among adolescent students. Symptom data collected from school-based asthma surveys conducted in Oakland, CA were used for case identification and determination of severity levels for students (high and low). Survey data were matched to Medicaid claims data for all asthma-related health care encounters for the year prior to the survey. We then employed recursive partitioning to develop classification trees that identified patterns of demographics and healthcare utilization associated with severity. A total of 561 students had complete matched data; 86.1% were classified as high-severity, and 13.9% as low-severity asthma. The classification tree consisted of eight subsets: three indicating high severity and five indicating low severity. The risk subsets highlighted varying combinations of non-specific demographic and socioeconomic predictors of asthma prevalence, morbidity and severity. For example, the subset with the highest class-prior probability (92.1%) predicted high-severity asthma and consisted of students without prescribed rescue medication, but with at least one in-clinic nebulizer treatment. The predictive accuracy of the tree-based model was approximately 66.7%, with an estimated 91.1% of high-severity cases and 42.3% of low-severity cases correctly predicted. Our analysis draws on the strengths of two complementary datasets to provide community-level information on children with asthma, and demonstrates the utility of recursive partitioning methods to explore a combination of features that convey asthma severity., Highlights • Community-level approaches to reduce asthma-related morbidity rely on local data sources. • Linkage of administrative data and surveys is an efficient way to obtain comprehensive data. • Recursive partitioning is a useful tool for exploring features that convey asthma severity. • The GUIDE partitioning algorithm provided asthma severity risk profiles based on the linked data.

ObjectiveTo explore possible associations of treatment with biological disease-modifying antirheumatic drugs (bDMARDs), including T-cell-based and interleukin-6 inhibition (IL-6i)-based therapies, and the risk for type 2 diabetes mellitus (T2DM) in patients with rheumatoid arthritis (RA).Study design, setting and participantsFive treatment groups were selected from a United States Electronic Medical Records database of 283 756 patients with RA (mean follow-up, 5 years): never received bDMARD (No bDMARD, n=125 337), tumour necrosis factor inhibitors (TNFi, n=34 873), IL-6i (n=1884), T-cell inhibitors (n=5935) and IL-6i+T cell inhibitor abatacept (n=1213). Probability and risk for T2DM were estimated with adjustment for relevant confounders.ResultsIn the cohort of 169 242 patients with a mean 4.5 years of follow-up and a mean 641 200 person years of follow-up, the adjusted probability of developing T2DM was significantly lower in the IL-6i (probability, 1%; 95% CI 0.6 to 2.0), T-cell inhibitor (probability, 3%; 95% CI 2.3 to 3.3) and IL-6i+T cell inhibitor (probability, 2%; 95% CI 0.1 to 2.9) groups than in the No bDMARD (probability, 5%; 95% CI 4.6 to 4.9) and TNFi (probability, 4%; 95% CI 3.7 to 4.7) groups. Compared with No bDMARD, the IL-6i and IL-6i+T cell inhibitor groups had 37% (95% CI of HR 0.42 to 0.96) and 34% (95% CI of HR 0.46 to 0.93) significantly lower risk for T2DM, respectively; there was no significant difference in risk in the TNFi (HR 0.99; 95% CI 0.93 to 1.06) and T-cell inhibitor (HR 0.96; 95% CI 0.82 to 1.12) groups.ConclusionsTreatment with IL-6i, with or without T-cell inhibitors, was associated with reduced risk for T2DM compared with TNFi or No bDMARDs; a less pronounced association was observed for the T-cell inhibitor abatacept.

Racial and ethnic segregation has been linked to a number of deleterious health outcomes, including violence. Previous studies of segregation and violence have focused on segregation between African Americans and Whites, used homicide as a measure of violence, and employed segregation measures that fail to take into account neighborhood level processes. We examined the relationship between neighborhood diversity and violent injury in Oakland, California. Violent injuries from the Alameda County Medical Center Trauma Registry that occurred between 1998 and 2002 were geocoded. A local measure of diversity among African American, White, Hispanic, and Asian populations that captured interactions across census block group boundaries was calculated from 2000 U.S. Census data and a Geographic Information System. The relationship between violent injuries and neighborhood level of diversity, adjusted for covariates, was analyzed with zero-inflated negative binomial regression. There was a significant and inverse association between level of racial and ethnic diversity and rate of violent injury (IRR 0.30; 95% CI: 0.13-0.69). There was a similar relationship between diversity and violent injury for predominantly African American block groups (IRR 0.23; 95% CI: 0.08-0.62) and predominantly Hispanic block groups (IRR 0.08; 95% CI: 0.01-0.76). Diversity was not significantly associated with violent injury in predominantly White or Asian block groups. Block group racial and ethnic diversity is associated with lower rates of violent injury, particularly for predominantly African American and Hispanic block groups.

Objective While tocilizumab (TCZ) is known to increase low-density lipoprotein (LDL) cholesterol levels, it is unclear whether TCZ increases cardiovascular risk in patients with rheumatoid arthritis (RA). This study was undertaken to compare the cardiovascular risk associated with receiving TCZ versus tumor necrosis factor inhibitors (TNFi). Methods To examine comparative cardiovascular safety, we conducted a cohort study of RA patients who newly started TCZ or TNFi using claims data from Medicare, IMS PharMetrics, and MarketScan. All patients were required to have previously used a different TNFi, abatacept, or tofacitinib. The primary outcome measure was a composite cardiovascular end point of hospitalization for myocardial infarction or stroke. TCZ initiators were propensity score matched to TNFi initiators with a variable ratio of 1:3 within each database, controlling for >65 baseline characteristics. A fixed-effects model combined database-specific hazard ratios (HRs). Results We included 9,218 TCZ initiators propensity score matched to 18,810 TNFi initiators across all 3 databases. The mean age was 72 years in Medicare, 51 in PharMetrics, and 53 in MarketScan. Cardiovascular disease was present at baseline in 14.3% of TCZ initiators and 13.5% of TNFi initiators. During the study period (mean ± SD 0.9 ± 0.7 years; maximum 4.5 years), 125 composite cardiovascular events occurred, resulting in an incidence rate of 0.52 per 100 person-years for TCZ initiators and 0.59 per 100 person-years for TNFi initiators. The risk of cardiovascular events associated with TCZ use versus TNFi use was similar across all 3 databases, with a combined HR of 0.84 (95% confidence interval 0.56–1.26). Conclusion This multi-database population-based cohort study showed no evidence of an increased cardiovascular risk among RA patients who switched from a different biologic drug or tofacitinib to TCZ versus to a TNFi.

Background: Most rheumatoid arthritis (RA) patients strive to consolidate their treatment from methotrexate combinations to monotherapy with the goal of the most effective and simplified therapy. Tocilizumab (TCZ) appears to have similar efficacy when used with or without concomitant csDMARDs in RA. Thus, it is clinically useful to predict treatment benefit among patients with RA starting TCZ monotherapy. Objectives: To identify RA patients most likely to achieve remission with TCZ monotherapy by developing and validating a prediction model through conventional regression and machine learning. Methods: We followed the TRIPOD recommendations for derivation and validation of clinical risk prediction models. Four TCZ monotherapy randomized controlled trials (RCT) in RA were identified (ACT-RAY, ADACTA, AMBITION, and FUNCTION) – two were chosen for derivation of the prediction models and two for validation. Relevant data for individual subjects from the trials were obtained, including demographics, RA characteristics, prior treatments, comorbid conditions, and baseline disease activity. In the two derivation trials, we examined each potential predictor of remission one at a time in logistic regression models, adjusted for age, sex, and baseline CDAI. The dependent variable in all models was CDAI ≤ 2.8 (remission) at 24 weeks. Three methods were used for variable selection: odds ratio (OR) based (forwarding variables to multivariable models if OR > 1.5 or Results: Baseline characteristics in the derivation (n=473) and validation (n=380) cohorts were generally similar: mean age 51.6 years in DC and 52.1 in VC; 77% female in DC and 83% in VC; mean baseline CDAI 39.8 in DC and 42.1 in VC; disease duration was longer in VC 3.6 years compared to 0.9 in DC. Seventy-eight patients (17%) reached remission in the DC; 49 (13%) in the VC. After testing possible variables in the derivation models, the variables selected as predictors of remission included younger age, male sex, lower baseline CDAI, shorter RA disease duration, region of world (Europe and South America increased odds of remission vs. Asia and North America), no previous exposure to DMARD/MTX, lower baseline HAQ-DI, and baseline hematocrit (see Table). In the DC, model fit and calibration were adequate in all three models, though discrimination was notably reduced under 10 fold cross-validation. The VC modeling suggested that all three models were similar in discrimination and were well calibrated (see Table). Conclusion: Different modeling strategies selected similar variables to predict remission using TCZ monotherapy: shorter disease duration, lower HAQ-DI, and no prior DMARD/methotrexate use. While these results should be interpreted with caution, as the analysis combined different studies that may represent different populations, they may provide guidance to clinicians tailoring treatment options based on baseline characteristics. Disclosure of Interests: Jamie Collins Grant/research support from: genentech, Fredrik Johansson Grant/research support from: Genentech, Sara Gale Shareholder of: Roche, Employee of: Genentech/Roche, Seoyoung Kim Grant/research support from: Pfizer, Bristol-Myers Squibb, Roche/Genentech and AbbVie., Swastina Shrestha Grant/research support from: Genentech, David Sontag Grant/research support from: Genentech, Jacklyn Stratton Grant/research support from: Genentech, Trinh Huong Shareholder of: Roche, Employee of: Genentech/Roche, Chang Xu Grant/research support from: Pfizer, Elena Losina Grant/research support from: Genentech, Pfizer, Samumed and Flexion, Consultant for: Regeneron, Daniel Solomon Grant/research support from: Abbvie, Amgen, Genentech, Janssen, and Pfizer

Background: Workplace abuse, including sexual harassment, is frequently experienced worldwide and is related to adverse mental health outcomes, and injuries. Flight attendants are an understudied occupational group and are susceptible to harassment due to working in a feminized, client-facing occupation with few protections or sanctioned responses against aggressive behaviors. Objective: We investigated the relationship between workplace abuse and health in a cohort of cabin crew. We also aimed to characterize perpetrator profiles. Methods: We conducted our study among 4,459U.S. and Canada-based participants from the Harvard Flight Attendant Health Study using multivariate logistic regression. Our exposures of interest were episodes of workplace abuse in the past year. We evaluated several mental and physical health outcomes, including depression, fatigue, musculoskeletal injuries, and general workplace injuries. Results: We report that exposures to verbal abuse, sexual harassment, and sexual assault are common among cabin crew, with 63, 26, and 2% of respondents, respectively, reporting harassment in the past year alone. Workplace abuse was associated with depression, sleep disturbances, and musculoskeletal injuries among male and female crew, with a trend toward increasing odds ratios (ORs) given a higher frequency of events. For example, sexual harassment was related to an increased odds for depression (OR = 1.91, 95% confidence interval [CI]: 1.51-2.30), which increased in a dose response-like manner among women reporting harassment once (OR = 1.44, 95% CI: 0.93-1.95), 2-3 times (OR = 1.83, 95% CI: 1.29-2.38), and 4 or more times (OR = 4.12, 95% CI: 3.18-5.06). We found that passengers were the primary perpetrators of abuse. Conclusions: Our study is the first to comprehensively characterize workplace abuse and harassment and its relation to health in a largely female customer-facing workforce. The strong associations with health outcomes observed in our study highlights the question of how workplace policies can be altered to mitigate prevalent abuses. Clinicians could also consider how jobs with high emotional labor demands may predispose people to adverse health outcomes, educate patients regarding their psychological/physical responses and coping strategies, and be aware of signs of distress in patients working in such occupations in order to direct them to the appropriate treatments and therapies.

OBJECTIVES: To compare treatment effectiveness in rheumatoid arthritis (RA) patients naïve to biological disease-modifying antirheumatic drugs (bDMARDs) treated with tocilizumab (TCZ) or TNF-inhibitor (TNFi) with (-combo) or without (-mono) conventional synthetic DMARDs (csDMARDs).METHODS: Patients with RA across 7 European registries, naïve to bDMARDs who initiated treatment with TCZ or TNFi from 2009 to 2016 were included. Drug retention rate was analyzed using Kaplan-Meier and Cox models, and CDAI over time by mixed models. The proportions of patients reaching CDAI low disease activity (LDA) and remission after one year were corrected for attrition.RESULTS: 6713 TNFi-combo, 3762 TNFi-mono, 646 TCZ-combo and 384 TCZ-mono were eligible. Crude median retention was 3.67 years (95%CI 3.41-3.83) for TNFi-combo, 4.14 (3.77-4.62) for TNFi-mono, 2.98 (2.76-3.34) for TCZ-combo and 3.63 years (3.34-5.03) for TCZ-mono. After adjustment for covariates, country and year of treatment initiation stratification, hazards of discontinuation were lower for TCZ-mono (0.60, 95% CI 0.52-0.69) and TCZ-combo (0.66, 95% CI 0.54-0.81) compared to TNFi-combo. Adjusted CDAI evolution was not significantly different between groups. CDAI LDA and remission corrected for attrition were similar between TCZ with or without csDMARDs and TNFi-combo.CONCLUSION: In routine care across 7 European countries, the adjusted drug retention, adjusted CDAI over time and attrition-corrected response proportion for RA patients were similar for bio-naïve patients if treated with TNFi-combo, TCZ-combo or TCZ-mono.

ObjectiveTo investigate the rate of serious bacterial, viral or opportunistic infection in patients with rheumatoid arthritis (RA) starting tocilizumab (TCZ) versus tumour necrosis factor inhibitors (TNFi) or abatacept.MethodsUsing claims data from US Medicare from 2010 to 2015, and IMS and MarketScan from 2011 to 2015, we identified adults with RA who initiated TCZ or TNFi (primary comparator)/abatacept (secondary comparator) with prior use of ≥1 different biologic drug or tofacitinib. The primary outcome was hospitalised serious infection (SI), including bacterial, viral or opportunistic infection. To control for >70 confounders, TCZ initiators were propensity score (PS)-matched to TNFi or abatacept initiators. Database-specific HRs were combined by a meta-analysis.ResultsThe primary cohort included 16 074 TCZ PS-matched to 33 109 TNFi initiators. The risk of composite SI was not different between TCZ and TNFi initiators (combined HR 1.05, 95% CI 0.95 to 1.16). However, TCZ was associated with an increased risk of serious bacterial infection (HR 1.19, 95% CI 1.07 to 1.33), skin and soft tissue infections (HR 2.38, 95% CI 1.47 to 3.86), and diverticulitis (HR 2.34, 95% CI 1.64 to 3.34) versus TNFi. An increased risk of composite SI, serious bacterial infection, diverticulitis, pneumonia/upper respiratory tract infection and septicaemia/bacteraemia was observed in TCZ versus abatacept users.ConclusionsThis large multidatabase cohort study found no difference in composite SI risk in patients with RA initiating TCZ versus TNFi after failing ≥1 biologic drug or tofacitinib. However, the risk of serious bacterial infection, skin and soft tissue infections, and diverticulitis was higher in TCZ versus TNFi initiators. The risk of composite SI was higher in TCZ initiators versus abatacept.

Background Flight attendants are an understudied occupational group, despite undergoing a wide range of adverse job-related exposures, including to known carcinogens. In our study, we aimed to characterize the prevalence of cancer diagnoses among U.S. cabin crew relative to the general population. Methods In 2014–2015, we surveyed participants of the Harvard Flight Attendant Health Study. We compared the prevalence of their self-reported cancer diagnoses to a contemporaneous cohort in the National Health and Nutrition Examination Survey (NHANES 2013–2014) using age-weighted standardized prevalence ratios (SPRs). We also analyzed associations between job tenure and the prevalence of selected cancers, using logistic regression and adjusting for potential confounders. Results Compared to NHANES participants with a similar socioeconomic status (n = 2729), flight attendants (n = 5366) had a higher prevalence of every cancer we examined, especially breast cancer, melanoma, and non-melanoma skin cancer among females. SPR for these conditions were 1.51 (95% CI: 1.02, 2.24), 2.27 (95% CI: 1.27, 4.06), and 4.09 (95% CI: 2.70, 6.20), respectively. Job tenure was positively related to non-melanoma skin cancer among females, with borderline associations for melanoma and non-melanoma skin cancers among males. Consistent with previous studies, we observed associations between job tenure and breast cancer among women who had three or more children. Conclusions We observed higher rates of specific cancers in flight attendants compared the general population, some of which were related to job tenure. Our results should be interpreted in light of self-reported health information and a cross-sectional study design. Future longitudinal studies should evaluate associations between specific exposures and cancers among cabin crew. Electronic supplementary material The online version of this article (10.1186/s12940-018-0396-8) contains supplementary material, which is available to authorized users.

Background Tocilizumab (TCZ) as monotherapy was more efficacious than the TNF inhibitor (TNFi) adalimumab as monotherapy for treatment of rheumatoid arthritis (RA) patients refractory to methotrexate (MTX) or in whom MTX was deemed inappropriate (ADACTA study).1 However, data are lacking regarding the comparative real life effectiveness of TCZ as monotherapy versus TNFi combined with conventional synthetic DMARDS (csDMARDs). Objectives To analyse treatment effectiveness by comparing drug retention rates and disease activity level in RA patients naive to biological DMARDs (bDMARDs) treated with TCZ as monotherapy (TCZ mono) or TNFi combined with csDMARDs (TNFi combo). Methods We included patients with RA across 10 European registries (TOCERRA collaboration) who were naive to bDMARDs and received treatment with either TCZ mono or TNFi combo from 2009 to 2016. Drug retention rate was analysed using a Kaplan–Meier model. The proportions of patients reaching CDAI low disease activity (LDA) and remission after one year were adjusted for attrition with the LUNDEX index.2 Results A total of 6315 patients were eligible, 253 on TCZ mono and 6062 on TNFi combo. Patients with TCZ mono were younger, smoked less, and used less glucocorticoids at baseline compared with TNFi combo patients (table 1). The crude median retention was 2.8 years (95% CI: 2.0–3.3) and 2.0 years (95% CI: 1.8–2.1) for TCZ mono and TNFi combo, respectively (p=0.21). At 1 year, the rates of LUNDEX corrected CDAI LDA (CDAI ≤10) and remission (CDAI ≤2.8) were similar between both groups (figure 1). The results were unchanged when considering the type of combination with csDMARDs and the dosage of MTX. Conclusions In routine care across 10 European countries, the retention and proportion of RA patients in LUNDEX corrected CDAI LDA and remission at 1 year were similar if treated with TCZ mono or TNFi combo. References [1] Gabay C, et al. Lancet2013;381:1541–50. doi:10.1016/S0140-6736(13)60250-0 [2] Kristensen LE, et al. Arthritis Rheum2006;54:600–6. doi:10.1002/art.21570 Disclosure of Interest K. Lauper: None declared, T. Kvien Grant/research support from: AbbVie, BMS, MSD, Pfizer, Roche and UCB, Consultant for: AbbVie, BMS, Celgene, Celltrion, Eli Lilly, Hospira, Merck-Serono, MSD, Orion Pharma, Pfizer, Roche, Sandoz and UCB, C. Codreanu: None declared, M. Hernandez: None declared, F. Ianonne: None declared, E. Kristianslund: None declared, G. Lukina Consultant for: BMS, Roche, MSD, AbbVie and Pfizer, D. Nordstrom Grant/research support from: AbbVie, BMS, MSD, Pfizer, Roche and UCB, Consultant for: AbbVie, BMS, MSD, Roche, UCB and Pfizer, K. Pavelka Grant/research support from: AbbVie, Roche, Medis, MSD and Pfizer, Consultant for: AbbVie, Roche, Amgen, MSD, BMS, UCB and Egis, Z. Rotar: None declared, M. Santos: None declared, S. Gale Employee of: Genentech, M. John Employee of: F. Hoffmann-La Roche, Y. Luder Employee of: F. Hoffmann-La Roche, D. Courvoisier: None declared, C. Gabay Grant/research support from: Roche, AbbVie, MSD and Pfizer, Consultant for: AbbVie, BMS, Roche, Pfizer, Celgene, MSD, Janssen Cilag, Amgen, UCB

Background In randomised controlled trials, subcutaneous tocilizumab (TCZ sc) has been found non-inferior to intravenous TCZ (TCZ iv) for the treatment of rheumatoid arthritis (RA) patients. However, to our knowledge, there are no observational studies comparing these two different routes of administration in routine care. Objectives To compare the real-world effectiveness of TCZ sc and TCZ iv in RA patients. Methods We included RA patients treated with TCZ from 8 European registries. We compared drug retention using Kaplan-Meier and Cox models. The proportions of patients achieving CDAI remission and low disease activity (LDA) at 1 year were compared using LUNDEX correction with computation of confidence intervals by bootstrapping.1 Results 2896 patients were retrieved from the collaborative registries before January 2017, including 2469 TCZ iv and 427 TCZ sc. Baseline demographics were similar between both groups, but patients in the TCZ iv group had a more severe disease activity, with higher DAS28, CDAI, tender joint count (TJC), swollen joint count (SJC), ESR and physician global assessment values (table 1). Crude median retention was 2.14 years (95% CI 2.03–2.33) for TCZ iv and 1.00 year for TCZ sc (95% CI 0.83–1.10), p 3.8%); CDAI LDA: 37.3% in TCZ iv vs.33.7% in TCZ sc (difference: −3.6%; bootstrap 95% CI: −9.4%; 2.5%)). Likewise, DAS28 remission and LDA at 1 year (LUNDEX corrected) were comparable between TCZ sc and TCZ iv (difference in DAS28 remission: −2.7%; bootstrap 95% CI: −8.8%; 3.5%; difference in DAS28 LDA: −5.8%; bootstrap 95% CI: −11.9%; 0.4%). Conclusions Drug retention and clinical effectiveness, assessed by CDAI and DAS28 changes and responses, were similar in both groups of patients, treated with TCZ sc or TCZ iv. Reference [1] Kristensen LE, et al. Arthritis Rheum2006;54:600–6. doi:10.1002/art.21570 Disclosure of Interest K. Lauper: None declared, M. Santos: None declared, F. Ianonne: None declared, Z. Rotar: None declared, D. Nordstrom Grant/research support from: AbbVie, BMS, MSD, Pfizer, Roche and UCB, Consultant for: AbbVie, BMS, MSD, Roche, UCB and Pfizer, C. Codreanu: None declared, T. Kvien: None declared, E. Kristianslund: None declared, K. Pavelka Grant/research support from: AbbVie, Roche, Medis, MSD and Pfizer, Consultant for: AbbVie, Roche, Amgen, MSD, BMS, UCB and Egis, G. Lukina Consultant for: BMS, Roche, MSD, AbbVie and Pfizer, M. Hernandez: None declared, S. Gale Employee of: Genentech, K. Sarsour Employee of: Genentech, Y. Luder Employee of: F. Hoffmann-La Roche, D. Courvoisier: None declared, C. Gabay Grant/research support from: Roche, AbbVie, MSD and Pfizer, Consultant for: AbbVie, BMS, Roche, Pfizer, Celgene, MSD, Janssen Cilag, Amgen, UCB

Background Few studies have conducted head-to-head comparisons of malignancy risk between different types of biologics in rheumatoid arthritis (RA). Objectives To examine the rate of incident malignancy excluding non-melanoma skin cancer (NMSC) in RA patients newly treated with tocilizumab (TCZ) versus TNF inhibitors (TNFi). Methods We conducted a cohort study using data from 3 U.S. healthcare claims databases (2010–2015) – Medicare, IMS PharMetrics Plus or Truven MarketScan. Adults aged ≥18 years with RA who newly started TCZ or a TNFi after failing a different TNFi, abatacept or tofacitinib were included. The primary outcome was incident malignancy excluding NMSC based on 2 diagnosis codes within 2 months (specificity >98%). The 10 most frequently occurring cancers, leukaemia and human papilloma virus-related cancer and all-cause mortality were analysed as individual secondary endpoints. (table 1). For the primary as-treated analysis, follow-up time started the day after cohort entry and ended on treatment discontinuation, outcome occurrence, disenrollment, death, or the end of study period. To control for >60 potential confounders, TCZ starters were propensity score (PS)-matched to TNFi starters with a variable ratio of 1:3 within each database. Hazard ratios (HR) from the 3 PS-matched cohorts were combined by a fixed-effects model. Results We included a total of 10,393 TCZ initiators PS-matched to 26,357 TNFi initiators. A total of 118 malignancies occurred in TCZ starters and 322 in TNFi starters across the three databases. The IR of malignancy per 100 person-years ranged from 0.81 (IMS) to 2.18 (Medicare) in TCZ and from 0.98 (MarketScan) to 2.16 (Medicare) in TNFi. The risk of incident malignancy was similar between the two groups across all three databases (table 1), with a combined HR of 0.92 (95% CI: 0.74 to 1.14) in TCZ versus TNFi. Secondary analyses by cancer subtype and all-cause mortality showed similar results. Conclusions This large multi-database cohort study found no difference in the risk of malignancy excluding NMSC in patients with RA who newly start TCZ versus TNFi. Disclosure of Interest S. Kim Grant/research support from: Roche, Pfizer, Bristol-Myers Squibb, A. Pawar : None declared, R. Desai: None declared, S. Gale Employee of: Genentech, M. Klearman Employee of: Genentech, K. Sarsour Employee of: Genentech, D. Solomon Grant/research support from: Roche, Pfizer, Lilly, Amgen, CORRONA, S. Schneeweiss Grant/research support from: Genentech/Roche, Boehringer Ingelheim, Consultant for: Aetion, WHISCON, LLC

ObjectiveTo compare the effectiveness of tocilizumab (TCZ) and tumour necrosis factor (TNF) inhibitors (TNFi) as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA) after the use of at least one biologic DMARD (bDMARD).MethodsWe included patients with RA having used at least one bDMARD from 10 European registries. We compared drug retention using Kaplan-Meier and Cox models and Clinical Disease Activity Index (CDAI) change over time with mixed-effects models for longitudinal data. The proportions of CDAI remission and low disease activity (LDA) at 1 year were compared using LUNDEX correction.Results771 patients on TCZ as monotherapy (TCZ mono), 1773 in combination therapy (TCZ combo), 1404 on TNFi as monotherapy (TNFi mono) and 4660 in combination therapy (TNFi combo) were retrieved. Crude median retention was higher for TCZ mono (2.31 years, 95% CI 2.07 to 2.61) and TCZ combo (1.98 years, 95% CI 1.83 to 2.11) than TNFi combo (1.37 years, 95% CI 1.30 to 1.45) and TNFi mono (1.31 years, 95% CI 1.18 to 1.47). In a country and year of treatment initiation-stratified, covariate-adjusted analysis, hazards of discontinuation were significantly lower among patients on TCZ mono or combo compared with patients on TNFi mono or combo, and TNFi combo compared with TNFi mono, but similar between TCZ mono and combo. Average adjusted CDAI change was similar between groups. CDAI remission and LDA rates were comparable between groups.ConclusionWith significantly longer drug retention and similar efficacy to TNFi combo, TCZ mono or combo are reasonable therapeutic options in patients with inadequate response to at least one bDMARD.

Introduction Treatment of giant cell arteritis (GCA) involves immediate initiation of high-dose glucocorticoid therapy with slow tapering of the dose over many months. Chronic exposure to glucocorticoids is associated with serious comorbidities. The objective of this analysis was to determine the glucocorticoid exposure and risk of glucocorticoid-related adverse events (AEs) in real-world patients with GCA. Methods Data from the Truven Healthcare MarketScan® database (from January 1, 2000, to June 30, 2015) and the Clinical Practice Research Datalink (CPRD; from January 1, 1995, to August 31, 2013) were used to retrospectively analyze patients aged ≥ 50 years with GCA in the USA and UK, respectively. Outcomes included oral glucocorticoid use (cumulative prednisone-equivalent exposure), glucocorticoid-related AEs and the association of AE risk with glucocorticoid exposure over 52 weeks. Results Of the 4804 patients in the US MarketScan database and 3973 patients in the UK CPRD database included, 71.3 and 74.6% were women and mean age was 73.4 and 73.0 years, respectively. Median starting glucocorticoid dose and cumulative glucocorticoid dose at 52 weeks were 20–50 mg/day and 4000–4800 mg, respectively. The most frequent glucocorticoid-related AEs were hypertension and eye, bone health, and glucose tolerance conditions. In the first year after diagnosis, the likelihood of any glucocorticoid-related AE was significantly increased for each 1 g increase in cumulative glucocorticoid dose in the US and UK cohorts (odds ratio [95% CI], 1.170 [1.063, 1.287] and 1.06 [1.03, 1.09], respectively; P

BACKGROUND: Sexual harassment and other types of workplace abuse are frequently experienced by workers worldwide and are related to adverse mental health outcomes and injuries. Flight attendants are an understudied occupational group and are susceptible to experiencing harassment due to working in a feminized, client-facing occupation with few protections or sanctioned responses against aggressive behaviors. In our study, we investigated the relationship between workplace verbal abuse, sexual harassment or sexual assault and health outcomes in a cohort of cabin crew. We also aimed to characterize perpetrator profiles according to type of abuse. METHODS: Among 4,459 participants from the Harvard Flight Attendant Health Study, we examined associations between episodes of workplace harassment or abuse in the past year (overall and by frequency of episodes) and a range of health outcomes using multivariate logistic regression. FINDINGS: We report that exposures to verbal abuse, sexual harassment and sexual assault are common among cabin crew, with rates of 63%, 26% and 2%, respectively, in the past year alone. Workplace abuse was associated with depression, sleep disturbances, and musculoskeletal injuries among male and female cabin crew, with a trend towards increasing odds ratios (ORs) given a higher frequency of events. For example, sexual harassment was related to an overall increased odds for depression (OR=1.91, 95% confidence interval [CI]: 1.51-2.30), which increased in a dose response-like manner among women who reported harassment once (OR=1.44, 95% CI: 0.93-1.95), 2-3 times (OR=1.83, 95% CI: 1.29-2.38), and 4 or more times (OR=4.12, 95% CI: 3.18-5.06). We found that passengers were the primary perpetrators of all types of abuse. INTERPRETATION: Our study is the first to comprehensively characterize sexual harassment and its relation to health in a largely female customer-facing workforce. Future research should track findings longitudinally and should compare results across professions. Funding: Flight Attendant Medical Research Institute. Declaration of Interest: The authors have no conflicts on interest to declare. Ethical Approval: This research was approved the Harvard T.H. Chan School of Public Health’s Institutional Review Board. All participants provided their written informed consent prior to enrollment in the study.

OBJECTIVE Using the UK Clinical Practice Research Datalink, we examined the incidence of glucocorticoid (GC)-related serious adverse events (SAEs) in rheumatoid arthritis (RA) and non-RA patients and quantified the risk of SAEs in patients with RA. METHODS We matched incident patients with RA to an age- and sex-matched, non-RA comparison group of equal size. In a cohort analysis, we estimated incidence rates (IRs) and IR ratios (IRRs) for GC-related AEs (i.e., diabetes mellitus [DM], osteoporosis, fractures, glaucoma, hypertension, gastrointestinal [GI] perforation or bleeding, thrombotic stroke or myocardial infarction [MI], or death), stratified by GC use. We conducted a series of nested case-control analyses among patients with RA, evaluating the effects of increasing cumulative and average daily GC dose. Cases of each outcome were matched to controls for age, sex, and general practice. We calculated adjusted odds ratios (ORs) with 95% confidence intervals (95% CIs) for each outcome. RESULTS Patients with RA had a higher incidence for all investigated SAEs except glaucoma, compared to non-RA patients. IRRs were greater in those patients prescribed a GC than in those without. In patients with RA, GCs were associated with an elevated risk of DM (adjusted OR 1.33 [95% CI 1.14-1.56]), osteoporosis (adjusted OR 1.41 [95% CI 1.25-1.59]), thrombotic stroke or MI (adjusted OR 1.28 [95% CI 1.07-1.52]), serious infection (adjusted OR 1.28 [95% CI 1.11-1.48]), and death (adjusted OR 1.33 [95% CI 1.19-1.48]). There was a trend of increasing risk with increasing cumulative and average daily GC dose for all outcomes other than glaucoma, hypertension, and GI perforations or bleeding (P < 0.05). CONCLUSION Patients with RA had an increased incidence of GC-related AEs. Increasing cumulative and average daily GC doses were found to be associated with an increasing risk of developing an AE.

Background While rheumatoid arthritis (RA) has been associated with the increased risk of developing type 2 diabetes mellitus (T2DM), few basic science studies have indicated the possible beneficial role of some biologic disease-modifying antirheumatic drugs (bDMARDs), including the interleukin-6 (IL-6) based DMARDs, on insulin resistance in patients with RA. Objectives To evaluate the impact of treatment with bDMARDs, including the IL-6 inhibitors, on the probability of developing T2DM in a real world setting. Methods From the Centricity Electronic Medical Records of GE Healthcare, a longitudinal cohort of 192,509 US adults (age≥18 years) with diagnosis of RA from January 2000 to April 2016 was selected. Patients were excluded if they had a prior history of diabetes, cancer and micro- or macro-vascular diseases at diagnosis of RA. Four mutually exclusive antirheumatic treatment groups (TGs) were identified by diagnosis date (Dx) and treatment initiation date (ID): tocilizumab (TCZ, n=843), TCZ+Other bDMARDs (TCZ+obDMARD, n=2489), non-TCZ other bDMARDs (obDMARD, n=45,262) and no bDMARD (n=143,915). Within the treatment groups, 142,225 patients had a minimum 6 months of exposure before development of T2DM or end of follow-up. Treatment-effects regression models were used to estimate the probabilities (95% CI) of developing T2DM during follow-up in the 4 TGs after adjusting and balancing with inverse-probability-weighted regression for various factors including age, sex, smoking status, body mass index, use of non-biologic DMARDs, use of statins, anaemia status and follow-up time post ID. Results At diagnosis, the 142,225 patients were on average 55 years old, 22% male, 71% white Caucasian, 13% with anaemia, and 32% obese with mean BMI of 29 kg/m 2 . About 28%/42% were using statins/MTX at diagnosis or during follow-up before development of T2DM. During mean 4.6 years of follow-up from Dx, 2.6%/2.6%/5.3%/5.8% developed T2DM in the TCZ/TCZ+obDMARD/obDMARD/no bDMARD TGs. The adjusted probability of developing T2DM was 0.05 (95% CI: 0.04, 0.05) in no bDMARD group; with significantly lower probability of developing T2DM in TCZ [0.02 (95% CI: 0.01, 0.04)], TCZ+obDMARD [0.03 (95% CI: 0.02, 0.04)] and obDMARD [0.01 (95% CI: 0.01, 0.02)] groups (Table). Hypertension, higher BMI and Statin use were associated with significantly higher probability of developing T2DM by 0.25 (95% CI: 0.16, 0.35), 0.08 (95% CI: 0.07, 0.08) and 0.36 (95% CI: 0.27, 0.47) respectively. Patients with anaemia had 8% higher likelihood of developing T2DM (p=0.13). Among those who received any bDMARD, those who ever received TCZ had significantly lower probability of developing T2DM (0.024, 95% CI: 0.02, 0.03), compared to those who were never exposed to TCZ therapy. Conclusions This study indicates the possible beneficial role of IL-6 inhibitors (TCZ) in reducing the likelihood of developing T2DM among adults without major co-morbidities at diagnosis of RA. Acknowledgements Funding by F. Hoffmann-La Roche/Genentech. Disclosure of Interest S. Paul Grant/research support from: Therapeutic Innovations Australia, O. Montvida: None declared, J. Best Employee of: Genentech, S. Gale Employee of: Genentech, A. Pethoe-Schramm Employee of: F. Hoffmann-La Roche, K. Sarsour Employee of: Genentech

Background Tocilizumab (TCZ) is a recombinant humanized monoclonal antibody targeted against the interleukin-6 receptor that was approved to treat rheumatoid arthritis (RA) in the EU in 2009 and in the US in 2010. TCZ has now completed long-term extension (LTE) follow-ups in a number of intravenous and subcutaneous RA trials. Objectives To provide an updated report on the incidence of safety events during TCZ treatment in patients with RA using data from multiple completed clinical trials and their LTEs, as well as to provide an update from the global TCZ postmarketing safety database. Methods Incidence and reporting rates of adverse events (AEs) of special interest, including infections, malignancies, anaphylaxis, bleeding events, myocardial infarctions, gastrointestinal perforations, strokes, hepatic events and demyelination, were estimated from 2 distinct patient data sets. Incidence rates were calculated from 12 completed TCZ RA clinical trials and their LTE periods and are reported as events per 100 patient-years (PY). Reporting rates were also estimated from the global TCZ postmarketing safety database (Oct 2008 to Oct 2015), which includes information from all spontaneously reported cases and non-interventional programs as well as literature cases, and are reported as cases per 100 patients. Results The clinical trial all-exposure population consisted of 7647 TCZ-treated patients with RA (81.6% female; mean [SD] age, 52 [12.6] years), constituting 22,394 PY (mean follow-up, 2.93 years) of exposure. The overall rate (95% CI) of serious AEs in the clinical trial population was 14.16 (13.67–14.66) per 100 PY. Overall incidence rates for individual events for the clinical trial population are reported in the Table and were consistent in each 6-month period over the 5-year duration. The global postmarketing population included 606,937 patients. The overall spontaneous reporting rate (range) of AEs of special interest in the postmarketing population was 9.37 (7.35–10.56) cases per 100 patients. Reporting rates of individual safety events of interest in the global postmarketing population are shown in the Table and were consistent in each 6-month period over the 7-year duration. Conclusions The safety profile of TCZ in the current analysis, which includes information about safety events from 12 clinical trials and their LTEs and across 7 years of real-world postmarketing reports encompassing $≈ $ 600,000 patients, was consistent with previous safety reports. These findings are consistent with the previously reported profile of TCZ and indicate that there is no evidence of increased safety risk with increasing exposure to TCZ. Acknowledgements This study was funded by F. Hoffmann-La Roche/Genentech, Inc. Disclosure of Interest S. Mohan Employee of: Genentech, Inc., M. Michalska Employee of: Genentech, Inc., J. Yourish Employee of: Genentech, Inc., J. Pei Employee of: Genentech, Inc., S. Gale Employee of: Genentech, Inc., C. Birchwood Employee of: Genentech, Inc., E. Berber Employee of: Genentech, Inc.

Background Tocilizumab (TCZ) as monotherapy has been shown to be more efficacious than the TNF inhibitor (TNFi) adalimumab as monotherapy in patients with rheumatoid arthritis (RA). However, effectiveness data comparing TCZ as monotherapy versus TNF inhibitors in combination with csDMARDs are limited. Objectives To examine retention of TCZ administered alone (TCZ mono) versus TNFi in combination with csDMARDs (TNFi combo) in patients with RA who had an inadequate response to ≥1 TNFi (TNFi-IR). Methods Patients with RA who were TNFi-IR and treated with TCZ mono or TNFi combo with baseline (BL) data, not immediately lost to follow-up and started treatment after TCZ was available across 9 European registries in TOCERRA from 2009 to 2016 were included. The hazard for TCZ discontinuation was modeled using a country-stratified Cox proportional hazards model, adjusting for age, gender, disease duration, seropositivity, HAQ and CDAI at BL, number of previous csDMARD and biologic DMARD (bDMARD), glucocorticosteroid and calendar year of treatment initiation. Missing data on covariates were imputed using multiple imputation with chained equations. Results A total of 4748 patients were eligible, including 585 who received TCZ mono and 4163 who received TNFi combo. Patients who received TCZ mono were older with a longer disease duration, more previous bDMARDs and less glucocorticosteroids at baseline (Table 1) compared with patients who received TNFi combo. The crude median retention for TCZ mono was 1.82 years (95% CI: 1.59–2.09) and 1.54 years (95% CI: 1.43–1.64) for TNFi combo, ( P =0.65). Causes of discontinuation differed between TCZ mono and TNFi combo ( P P Conclusions In routine care across 9 European countries, TCZ mono retention is better than TNFi combo in patients with RA who were TNFi-IR. Acknowledgements Funding by F. Hoffmann-La Roche/Genentech. Disclosure of Interest K. Lauper: None declared, D. Nordstrom Grant/research support from: AbbVie, BMS, MSD, Pfizer, Roche and UCB, Consultant for: AbbVie, BMS, MSD, Roche, UCB and Pfizer, K. Pavelka Grant/research support from: AbbVie, Roche, Medis, MSD and Pfizer, Consultant for: AbbVie, Roche, Amgen, MSD, BMS, UCB and Egis, V. Hernandez: None declared, M. J. Santos: None declared, Z. Rotar: None declared, F. Iannone: None declared, C. Codreanu: None declared, G. Lukina Consultant for: BMS, Roche, MSD, AbbVie and Pfizer, S. Gale Employee of: Genentech, K. Sarsour Employee of: Genentech, A. Pethoe-Schramm Employee of: F. Hoffmann-La Roche, D. Courvoisier: None declared, C. Gabay Grant/research support from: AB2 Bio, AbbVie, Actelion, BMS, Debiopharm, MSD, Novartis, Pfizer, Regeneron, Roche, Sanofi and UCB, Consultant for: AB2 Bio, AbbVie, Actelion, BMS, Debiopharm, MSD, Novartis, Pfizer, Regeneron, Roche, Sanofi and UCB

Background There have been conflicting reports whether patients with rheumatoid arthritis (RA) receiving conventional or biologic immunosuppressive therapies are at increased risk of specific malignancies. Melanoma is an aggressive malignancy with risk factors including sex, age, fair skin and elevated cumulative UV exposure. Interleukin-6 (IL-6) has a role in pro- and antitumorigenic pathways. Whether tocilizumab (TCZ), a biologic that alters IL-6 signaling, increases the risk of melanoma in patients with RA is unclear. Objectives This age- and sex-adjusted standardized incidence ratio (SIR) analysis compared the observed reports of melanoma in patients with RA treated with TCZ in clinical trial and postmarketing settings with the expected number of cases across geographic regions. Methods SIRs for melanoma were calculated from the TCZ clinical trials all-exposure population. Postmarketing rates were estimated from the TCZ Global Safety Database population. Both databases were searched cumulatively from 11 April 2005 to 10 October 2015. For clinical trials, observed reports of melanoma in patients with RA treated with TCZ were compared with expected number of cases in the general population based on the 2012 US Surveillance, Epidemiology, and End Results using an age- and sex-adjusted SIR. Postmarketing regional SIRs were calculated based on the estimated commercial exposure in each region and the incidence of melanoma as reported by Globocan by age and sex (2012). Crude postmarketing rates were age- and sex-adjusted according to the clinical trial demographic profile to estimate the expected number of cases of melanoma in each region. Results In the clinical trial setting, 4 qualifying cases of melanoma were identified among 7093 patients with RA treated with TCZ (20,828 PY of exposure). The SIR estimate (0.71 [95% CI, 0.19–1.81]) for melanoma incidence in patients with RA treated with TCZ in clinical trials was comparable to that in the general population (Table 1). In the postmarketing setting, the number of observed reports of melanoma was comparable to the expected number of cases in Europe and Japan and fewer than expected in North America (Table 2). The exception is Australia, where SIR estimates indicated more than the expected number of cases in patients with RA receiving TCZ in Australia compared with the general population in that region (SIR 3.71 [95% CI: 2.16, 5.93]). Conclusions In clinical trials, no evidence was found to suggest there were more cases of melanoma than expected in patients with RA treated with TCZ compared with the general population. Consistent with this, no evidence was found to suggest that patients with RA treated with TCZ in Europe, North America or Japan had more cases of melanoma than expected compared with the general population in each region. In contrast, the estimated SIR of melanoma in patients with RA treated with TCZ in Australia indicated more than the expected number of cases in the general population. This finding is consistent with reports of elevated risk of melanoma in patients with RA in Australia (compared with the general population), where UV exposure is high and methotrexate is a common first-line therapy.1,2 References Buchbinder et al. Arthritis Rheum. 2008. Buchbinder et al. BMC Musculoskelet Disord. 2015. Acknowledgements Funded by Roche/Genentech. Disclosure of Interest S. Gale Employee of: Genentech, J. Wang Employee of: Roche, J. Nebesky Employee of: Roche, A. Linke Employee of: Genentech, E. Berber Employee of: Genentech

Background To evaluate the impact of treatment with disease-modifying antirheumatic drugs (DMARDs), including IL-6 receptor inhibitor tocilizumab (TCZ), on anaemia markers in patients with rheumatoid arthritis. Methods Using the Centricity Electronic Medical Records from USA, patients with rheumatoid arthritis diagnosed between January 2000 and April 2016, who initiated TCZ ( n = 3732); tofacitinib (TOFA, n = 3126); other biologic DMARD (obDMARD, n = 55,964); or other non-biologic DMARD (onbDMARD, n = 91,236) were identified. Changes in haemoglobin (Hb) and haematocrit (Hct) over 2 years of treatment initiation were evaluated, adjusting and balancing for confounders. Results Mean (95% CI) adjusted increase in Hb and Hct levels at 24 months in TCZ group were 0.23g/dL (0.14, 0.42) and 0.96% (0.41, 1.52) respectively. Among patients with anaemia in the TCZ group, Hb and Hct increased significantly by 0.72g/dL and 2.06%, respectively. Patients in the TCZ group were 86% (95% CI of OR: 1.43, 2.00) more likely to increase Hb ≥ 1g/dL compared to the other groups combined. No clinically significant changes in Hb were observed in the other groups. The obDMARD group demonstrated lower Hct increase than TCZ group, while no significant changes were observed in the remaining groups. Compared to those who initiated TCZ therapy after 1 year of diagnosis of rheumatoid arthritis, those who initiated earlier were 95% (OR = 1.95; 95% CI: 1.19, 3.21; p Conclusions This real-world study suggests significant increase in Hb and Hct levels after TCZ therapy in anaemic and non-anaemic patients with rheumatoid arthritis, compared with other biologic and non-biologic DMARDs.

Despite large public investments in asthma interventions, there are few rigorous assessments of these programmes and little understanding of what comprises an effective intervention. There is a lack of appropriate data, little technical support is provided, and the programs themselves have little incentive to conduct these analyses. In this study, we apply optimal full matching using propensity scores to estimate the impact of an asthma intervention programme across a range of health outcomes. Our participation model is derived using the Deletion, Substitution and Addition (DSA) algorithm, a method used in epidemiology for model selection. We find that the asthma programme in question has no significant effect on participants that distinguishes them from matched nonparticipants, but it is not clear whether this is due to the effectiveness of the programme, heterogeneity of effects or barriers outside the programme's control. Our findings do show how current programmes could be modified to increase their e...

Background Women have elevated rates of thyroid disease compared to men. Environmental toxicants have been implicated as contributors to this dimorphism, including polybrominated diphenyl ethers (PBDEs), flame retardant chemicals that disrupt thyroid hormone action. PBDEs have also been implicated in the disruption of estrogenic activity, and estrogen levels regulate thyroid hormones. Post-menopausal women may therefore be particularly vulnerable to PBDE induced thyroid effects, given low estrogen reserves. The objective of this study was to test for an association between serum PBDE concentrations and thyroid disease in women from the United States (U.S.), stratified by menopause status. Methods Serum PBDE concentrations (BDEs 47, 99, 100 and 153) from the National Health and Examination Survey (NHANES) and reports on thyroid problems were available in the NHANES 2003–2004 cycle. Odds ratios (ORs) were calculated using multivariate logistic regression models accounting for population-weighted survey techniques and controlling for age, body mass index (BMI), education, smoking, alcohol consumption and thyroid medication. Menopause status was obtained by self-reported absence of menstruation in the previous 12 months and declared menopause. Results Women in the highest quartile of serum concentrations for BDEs 47, 99, and 100 had increased odds of currently having thyroid disease (ORs: 1.5, 1.8, 1.5, respectively) compared to the reference group (1st and 2nd quartiles combined); stronger associations were observed when the analysis was restricted to postmenopausal women (ORs: 2.2, 3.6, 2.0, respectively). Conclusion Exposure to BDEs 47, 99, and 100 is associated with thyroid disease in a national sample of U.S. women, with greater effects observed post-menopause, suggesting that the disruption of thyroid signaling by PBDEs may be enhanced by the altered estrogen levels during menopause. Electronic supplementary material The online version of this article (doi:10.1186/s12940-016-0141-0) contains supplementary material, which is available to authorized users.

Exposure to neighborhood factors remains difficult to quantify when neighborhoods are often predefined and imprecisely measured. This study examines the association between neighborhood deprivation and participation in a community-based asthma case management (CM) program in Oakland, CA. We estimated neighborhoods by calculating walking distances of , and miles around each child's (n=2892) residence. The model assesses deprivation by the addition of weighted factors within a child's neighborhood-crime rates, alcohol outlets, and eight 2000 US Census characteristics. The results illustrate that neighborhood deprivation is weakly associated with greater levels of program participation, but neighborhood education level, measured by percentage of residents with less than a high school education, is strongly associated with greater program participation (OR: 4.43, 95% CI: [1.23, 15.99]). Neighborhood deprivation factors were significantly different between neighborhoods defined by walking distances and census blockgroups (Wilcoxon-signed rank test: p

This paper has two aims: (1) to summarize various geographic information science methods; and (2) to provide a review of studies that have employed such methods. Though not meant to be a comprehensive review, this paper explains when certain methods are useful in epidemiological studies and also serves as an overview of the growing field of spatial epidemiology.

For pediatric populations, schools are considered effective platforms to establish comprehensive asthma surveillance campaigns, particularly in communities with disproportionate prevalence of disea...

Previous studies have found associations between air pollution, specifically particulate matter, with preterm birth. Additionally, the associations are stronger in neighborhoods with low neighborho...

Background Few studies have examined the broad health effects of occupational exposures in flight attendants apart from disease-specific morbidity and mortality studies. We describe the health status of flight attendants and compare it to the U.S. population. In addition, we explore whether the prevalence of major health conditions in flight attendants is associated with length of exposure to the aircraft environment using job tenure as a proxy. Methods We surveyed flight attendants from two domestic U.S. airlines in 2007 and compared the prevalence of their health conditions to contemporaneous cohorts in the National Health and Nutrition Survey (NHANES), 2005-2006 and 2007-2008. We weighted the prevalence of flight attendant conditions to match the age distribution in the NHANES and compared the two populations stratified by gender using the Standardized Prevalence Ratio (SPR). For leading health conditions in flight attendants, we analyzed the association between job tenure and health outcomes in logistic regression models. Results Compared to the NHANES population (n =5,713), flight attendants (n = 4,011) had about a 3-fold increase in the age-adjusted prevalence of chronic bronchitis despite considerably lower levels of smoking. In addition, the prevalence of cardiac disease in female flight attendants was 3.5 times greater than the general population while their prevalence of hypertension and being overweight was significantly lower. Flight attendants reported 2 to 5.7 times more sleep disorders, depression, and fatigue, than the general population. Female flight attendants reported 34% more reproductive cancers. Health conditions that increased with longer job tenure as a flight attendant were chronic bronchitis, heart disease in females, skin cancer, hearing loss, depression and anxiety, even after adjusting for age, gender, body mass index (BMI), education, and smoking. Conclusions This study found higher rates of specific diseases in flight attendants than the general population. Longer tenure appears to explain some of the higher disease prevalence. Conclusions are limited by the cross-sectional design and recall bias. Further study is needed to determine the source of risk and to elucidate specific exposure-disease relationships over time.

Background Rheumatoid arthritis (RA) is a chronic, erosive form of inflammatory arthritis characterized by a distinctive pattern of bone and joint destruction. Along with disease-modifying antirheumatic drugs and newer biologic therapy, treatment can include oral corticosteroids (oCS), predominantly prednisolone or prednisone. CS are associated with a variety of adverse effects. 1 Objectives Using data from the UK9s Clinical Practice Research Datalink, we estimated the incidence rates (IRs) and incidence rate ratios (IRRs) of known oCS-related serious adverse events (SAEs) of interest in an RA cohort and in a non-RA general population (GP) comparison group matched on age, sex, and time. We also explored the role of oCS use on the risk for SAEs of interest by comparing RA patients of varying exposure levels of oCS. Methods Patients with a first-time diagnosis of RA who were ≥18 years of age were identified and matched to patients in a non-RA GP comparison group of equal size. Group IRs and IRRs were estimated for diabetes, osteoporosis, fractures, glaucoma, hypertension, thrombotic stroke or myocardial infarction (MI), gastrointestinal (GI) perforation or bleeding, and death for the RA group and the GP group. We then performed a series of nested case-control analyses examining the effect of oCS use on the risk for SAEs of interest. We used conditional logistic regression to calculate the unadjusted and multivariate adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for the association between oCS use and the risk for each separate outcome of interest. We stratified the analyses according to increasing cumulative and average daily oCS use. Results The cohort consisted of 34,047 RA patients and 34,047 matched non-RA GP patients. Mean follow-up time was ∼8 years. The incidence for most SAEs was greater in the RA group than in the GP group. IRRs (95% CIs) for SAEs of interest were diabetes (1.21; 1.13–1.31), osteoporosis (2.11; 1.96–2.27), fractures (1.16; 1.08–1.24), glaucoma (1.08; 0.94–1.22), hypertension (1.13; 1.09–1.18), thrombotic stroke or MI (1.22; 1.11–1.34), GI perforation or bleeding (1.3; 1.15–1.47), and death (1.17; 1.11–1.22). In multivariate analyses, increasing risks for diabetes, osteoporosis, fractures, thrombotic stroke or MI, and death were observed with increasing cumulative oCS use ( p 7.5 mg/day had an increased adjusted OR (95% CI) for diabetes (1.49; 1.21–1.84), osteoporosis (1.41; 1.20–1.66), fractures (1.22; 1.03–1.45), thrombotic stroke or MI (1.61; 1.27–2.04), and death (1.49; 1.27–1.74). Conclusions Patients with RA experienced an increased incidence of diabetes, osteoporosis, fractures, hypertension, thrombotic stroke or MI, GI perforation or bleeding, and death compared with age- and sex-matched controls. Increasing cumulative oCS doses and average daily oCS doses were associated with increased odds of diabetes, osteoporosis, fractures, thrombotic stroke or MI, and death. References Venables PJW. Rheumatoid arthritis treatment (beyond the basics). UpToDate, Inc. 2016. http://www.uptodate.com/contents/rheumatoid-arthritis-treatment-beyond-the-basics.Accessed January 21, 2016. Disclosure of Interest J. Wilson: None declared, K. Sarsour Shareholder of: Roche, Employee of: Roche, S. Gale Shareholder of: Roche, Employee of: Roche, A. Petho-Schramm Employee of: F. Hoffmann-La Roche, S. Jick: None declared, C. Meier Shareholder of: Hoffmann-La Roche, Grant/research support from: Hoffmann-La Roche

Background In the United States, systemic sclerosis (SSc) develops in adults at an annual estimated incidence rate of 20 cases per million, and the estimated prevalence is 240 cases per million. 1 Published research on the epidemiology of SSc and common treatments for US SSc patient cohorts is limited. In general, SSc patients are treated based on their specific organ involvement; patients with diffuse skin involvement or severe organ involvement, or both, are treated with systemic immunosuppressive therapy. Objectives To understand the treatment patterns for and the real-world use of immunosuppressive drugs in adults with SSc using data from a large US healthcare claims database. Methods The analysis is a retrospective cohort study of patients with SSc diagnosed from 2006 to 2012 using data from Truven Health MarketScan® Research Databases, a medical insurance claims database of insured active employees and their dependents, early retirees, Medicare-eligible retirees, and Medicaid recipients. An SSc diagnosis was determined by ≥1 inpatient claim for an SSc diagnosis ( ICD-9 710.1) or ≥2 outpatient claims for an SSc diagnosis. During the study time period, patients were allowed enrollment gaps of ≤30 days but had to have enrollment data 6 months before and 12 months after the SSc diagnosis. Results The prevalence of SSc in the MarketScan database from 2006 to 2013 ranged from 204 to 247 cases per million adults who were actively enrolled in health insurance plans. There were 6872 patients ≥18 years of age diagnosed with and treated for SSc during the study time period. Eighty-six percent of the treated SSc population were female, and the average age of the cohort was 54 years. The most common medication claims among patients in the first year after an SSc diagnosis were for antibiotics (54%), opioids (44%), corticosteroids (40%), and proton pump inhibitors (PPIs) (31%). Approximately 30% of SSc patients initiated ≥1 of the following disease-modifying antirheumatic drugs (DMARDs), alone or in combination, in the first year after the SSc index, with a median time to initiation of 70 days: methotrexate (21%), mycophenolate mofetil (17%), biologics (3%), cyclophosphamide (2%), or other DMARDs (62% of which included azathioprine, chloroquine, cyclosporine, hydroxychloroquine, penicillamine, quinacrine, and sulfasalazine). Among patients who filled a DMARD prescription in the first year, 15% switched to a second type of DMARD. Of the 70% of patients who did not fill a prescription for DMARD in the first year after the SSc index, 63% filled prescriptions for antibiotics, 56% opioids, 33% corticosteroids, 26% PPIs, 20% NSAIDs, 10% ACE inhibitors, 10% calcium antagonists, 5% prokinetics, 1% ERA, and Conclusions These data show that the prevalence of SSc among adults in a US healthcare claims population is consistent with the estimated US prevalence. Most SSc patients do not initiate DMARD treatment in the first year after diagnosis, and most SSc patients have received antibiotics, opioids, and systemic corticosteroids. References Mayes MD et al. Prevalence, incidence, survival, and disease characteristics of systemic sclerosis in a large US population. Arthritis Rheum. 2003;48:2246–2255. Disclosure of Interest S. Gale Shareholder of: Roche, Employee of: Roche, N. Mathew: None declared, C. Lin: None declared, A. Jahreis: None declared, K. Sarsour Shareholder of: Roche, Employee of: Roche

Background Anemia, a common complication of RA, has a negative impact on RA symptoms and QOL and is associated with a more severe form of RA. Roles of biologic DMARDs (BDMARDs), including the IL-6 pathway–inhibiting biologic tocilizumab (TCZ), in the pathophysiology of anemia have not been well explored at the population level. Objectives Evaluate the impact of treatment (Tx) with nonbiologic (NB) and BDMARDs on hemoglobin (Hb) and hematocrit (Hct) in a real-world setting. Methods Using the GE EMR database, a longitudinal cohort study was conducted on 153,672 adult RA pts in the US who had ≥6-mo follow-up. 4 mutually exclusive DMARDTx groups (TxGs) were identified: TCZ, tofacitinib (TOFA), other BDMARDs (OBDMARD), and other NBDMARDs (ONBDMARD). To evaluate changes in Hb and Hct at 6 and 12 mo from index date (ID) in different TxGs, unadjusted and adjusted mean (95% CI) changes were obtained, adjusting for age, sex, smoking status, RA duration, concomitant medications, CRP, and other covariates. Separate analyses were conducted for pts with Hb Results Demographics of the cohort were: 55 y mean age, 76% female, 59% white, 57% current or ex-smokers, 44% obese (mean BMI 30 kg/m 2 ). 2% of pts had ischemic heart disease, 2% renal disease, and 7% diabetes. Mean Hb and Hct levels at ID across TxGs were 13.3 g/dL and 40%. Average CRP (1.6 mg/dL) and ESR (23 mm/h) were clinically similar across TxGs at ID. Adjusting for covariates, increases in Hb and Hct levels at 6 and 12 mo were significantly higher in the TCZ group vs the other TxGs (Table). Among anemic pts at ID, increases in Hb and Hct at 6 mo were significantly higher in the TCZ group vs the other TxGs. Significantly greater reductions in ESR and CRP levels over all follow-up periods were observed in the TCZ group vs the other TxGs. Conclusions This study suggests significant increases in Hb and Hct levels after TCZ therapy vs other nonbiologic and biologic therapies in RA pts with anemia, in line with the potential role of IL-6 in RA pts with anemia. Further study is needed to better evaluate the role of IL-6–based OBDMARDs as a Tx option for RA pts with anemia. Disclosure of Interest S. Paul Grant/research support from: Genentech, AstraZeneca, Novo Nordisk, Consultant for: GI Dynamics, Speakers bureau: AstraZeneca, GI Dynamics, Novo Nordisk, K. Klein Grant/research support from: Genentech, AstraZeneca, Novo Nordisk, Consultant for: GI Dynamics, J. Best Shareholder of: Roche, Employee of: Genentech, S. Gale Shareholder of: Roche, Employee of: Roche, A. Petho-Schramm Employee of: F. Hoffmann-La Roche, K. Sarsour Shareholder of: Roche, Employee of: Roche

Polycyclic aromatic hydrocarbons (PAHs) are found widely in the ambient air and result from combustion of various fuels and industrial processes. PAHs have been associated with adverse human health effects such as cognitive development, childhood IQ, and respiratory health. The Fresno Asthmatic Children’s Environment Study (FACES) enrolled 315 children ages 6-11 years with asthma in Fresno, CA and followed the cohort from 2000 to 2008. Subjects were evaluated for asthma symptoms in up to three 14-day panels per year. Detailed ambient pollutant concentrations were collected from a central site and outdoor pollutants were measured at 83 homes for at least one 5-day period. Measurements of particle-bound PAHs were used with land use regression models to estimate individual exposures to PAHs with 4-, 5- or 6-member rings (PAH456) and phenanthrene for the cohort (approximately 22 000 individual daily estimates). We used a cross-validation based algorithm for model fitting and a generalized estimated equation approach to account for repeated measures. Multiple lags and moving averages of PAH exposure were associated with increased wheeze for each of the three types of PAH exposure estimates. The odds ratios for asthmatics exposed to PAHs (ng/m3) ranged from 1.01 (95% CI, 1.00-1.02) to 1.10 (95% CI, 1.04-1.17)]. This trend for increased wheeze persisted among all PAHs measured. Phenanthrene was found to have a higher relative impact on wheeze. These data provide further evidence that PAHs contribute to asthma morbidity.

Background and Aims: Few studies about the health consequences of flight attendant work exist, even though attending and safeguarding passengers is demanding work, usually involving circadian rhyth...