Laura Horne

Safety of saxagliptin: rationale for and design of a series of postmarketing observational studies.

To describe the design and rationale of a series of postmarketing studies to examine the safety of saxagliptin, an oral dipeptidyl peptidase‐4 inhibitor for the treatment of type 2 diabetes mellitus, in real‐world settings.

Methodological Challenges When Comparing Demographic and Clinical Characteristics of International Observational Registries.

Comparisons of data from different registries can be helpful in understanding variations in many aspects of rheumatoid arthritis (RA). The study aim was to assess and improve the comparability of demographic, clinical, and comorbidity data from 5 international RA registries.

Can rheumatoid arthritis (RA) registries provide contextual safety data for modern RA clinical trials? The case for mortality and cardiovascular disease

Background We implemented a novel method for providing contextual adverse event rates for a randomised controlled trial (RCT) programme through coordinated analyses of five RA registries, focusing here on cardiovascular disease (CVD) and mortality. Methods Each participating registry (Consortium of Rheumatology Researchers of North America (CORRONA) (USA), Swedish Rheumatology Quality of Care Register (SRR) (Sweden), Norfolk Arthritis Register (NOAR) (UK), CORRONA International (East Europe, Latin America, India) and Institute of Rheumatology, Rheumatoid Arthritis (IORRA) (Japan)) defined a main cohort from January 2000 onwards. To address comparability and potential bias, we harmonised event definitions and defined several subcohorts for sensitivity analyses based on disease activity, treatment, calendar time, duration of follow-up and RCT exclusions. Rates were standardised for age, sex and, in one sensitivity analysis, also HAQ. Results The combined registry cohorts included 57 251 patients with RA (234 089 person-years)—24.5% men, mean (SD) baseline age 58.2 (13.8) and RA duration 8.2 (11.7) years. Standardised registry mortality rates (per 100 person-years) varied from 0.42 (CORRONA) to 0.80 (NOAR), with 0.60 for RCT patients. Myocardial infarction and major adverse cardiovascular events (MACE) rates ranged from 0.09 and 0.31 (IORRA) to 0.39 and 0.77 (SRR), with RCT rates intermediate (0.18 and 0.42), respectively. Additional subcohort analyses showed small and mostly consistent changes across registries, retaining reasonable consistency in rates across the Western registries. Additional standardisation for HAQ returned higher mortality and MACE registry rates. Conclusions This coordinated approach to contextualising RA RCT safety data demonstrated reasonable differences and consistency in rates for mortality and CVD across registries, and comparable RCT rates, and may serve as a model method to supplement clinical trial analyses for drug development programmes.

How comparable are rates of malignancies in patients with rheumatoid arthritis across the world? A comparison of cancer rates, and means to optimise their comparability, in five RA registries

BACKGROUND The overall incidence of cancer in patients with rheumatoid arthritis (RA) is modestly elevated. The extent to which cancer rates in RA vary across clinical cohorts and patient subsets, as defined by disease activity or treatment is less known but critical for understanding the safety of existing and new antirheumatic therapies. We investigated comparability of, and means to harmonise, malignancy rates in five RA registries from four continents. METHODS Participating RA registries were Consortium of Rheumatology Researchers of North America (CORRONA) (USA), Swedish Rheumatology Quality of Care Register (SRR) (Sweden), Norfolk Arthritis Register (NOAR) (UK), CORRONA International (several countries) and Institute of Rheumatology, Rheumatoid Arthritis (IORRA) (Japan). Within each registry, we analysed a main cohort of all patients with RA from January 2000 to last available data, and sensitivity analyses of sub-cohorts defined by disease activity, treatment change, prior comorbidities and restricted by calendar time or follow-up, respectively. Malignancy rates with 95% CIs were estimated, and standardised for age and sex, based on the distributions from a typical RA clinical trial programme population (fostamatinib). RESULTS There was a high consistency in rates for overall malignancy excluding non-melanoma skin cancer (NMSC), for malignant lymphomas, but not for all skin cancers, across registries, in particular following age/sex standardisation. Standardised rates of overall malignancy excluding NMSC varied from 0.56 to 0.87 per 100 person-years. Within each registry, rates were generally consistent across sensitivity analyses, which differed little from the main analysis. CONCLUSION In real-world RA populations, rates of both overall malignancy and of lymphomas are consistent.

Using epidemiological registry data to provide background rates as context for adverse events in a rheumatoid arthritis drug development program: a coordinated approach†

Observational studies can provide context for adverse events observed in clinical trials, especially for infrequent events or long‐term risks. We developed methods to improve safety contextualization for a rheumatoid arthritis drug development program through coordinated analyses of multiple registries.

Infection rates in patients from five rheumatoid arthritis (RA) registries: contextualising an RA clinical trial programme

Objective Patients with rheumatoid arthritis (RA) have an increased risk of serious infections. Comparing infection rates across RA populations is complicated by differences in background infection risk, population composition and study methodology. We measured infection rates from five RA registries globally, with the aim to contextualise infection rates from an RA clinical trials population. Methods We used data from Consortium of Rheumatology Research of North America (CORRONA) (USA), Swedish Rheumatology Quality of Care Register (Sweden), Norfolk Arthritis Register (UK), CORRONA International (multiple countries) and Institute of Rheumatology Rheumatoid Arthritis (Japan) and an RA clinical trial programme (fostamatinib). Within each registry, we analysed a main cohort of all patients with RA from January 2000 to last available data. Infection definitions were harmonised across registries. Sensitivity analyses to address potential confounding explored subcohorts defined by disease activity, treatment change and/or prior comorbidities and restriction by calendar time or follow-up. Rates of infections were estimated and standardised to the trial population for age/sex and, in one sensitivity analysis also, for Health Assessment Questionnaire (HAQ) score. Results Overall, age/sex-standardised rates of hospitalised infection were quite consistent across registries (range 1.14–1.62 per 100 patient-years). Higher and more consistent rates across registries and with the trial programme overall were seen when adding standardisation for HAQ score (registry range 1.86–2.18, trials rate 2.92) or restricting to a treatment initiation subcohort followed for 18 months (registry range 0.99–2.84, trials rate 2.74). Conclusion This prospective, coordinated analysis of RA registries provided incidence rate estimates for infection events to contextualise infection rates from an RA clinical trial programme and demonstrated relative comparability of hospitalised infection rates across registries.

THU0138 The Corrona International Rheumatoid Arthritis Registry: Variations in Disease Activity and Management Across Participating Regions

Background To date, there is no multinational Rheumatoid Arthritis (RA) registry uniformly collecting longitudinal data. The CORRONA International (CI) registry was developed to address this need. Objectives To explore variations in RA disease (dx) activity and drug utilization across regions participating in CI RA registry and the US CORRONA RA registry. Methods The CI registry, launched in September 2011, is a multi-center, longitudinal, observational registry collecting data on demographics, lifestyle characteristics, anthropometry, medication exposures, adverse events and toxicities from rheumatologists and RA patients (pts) at regular clinical encounters. Adult RA pts have been enrolled in 10 countries in 3 regions [Eastern Europe: Poland, Czech Republic, Hungary, Romania, Russia, Ukraine; Latin America: Mexico, Brazil, Argentina; Asia: India]. We present baseline descriptive data including: variations in biologic and DMARD utilization, dx activity and functionality across the regions participating in both registries. Results As of Nov 2012, 4042 patients had been enrolled in CI. Table 1 shows variations in dx characteristics among the CI regions and the USA. In general, dx activity is higher but functionality and biologic drug utilization is lower in CI regions compared to USA. Biologics use is still very rare in India. Conclusions The CI registry reveals differences in the management of RA across different global regions. The ongoing recruitment and follow-up of more pts will enable association studies between therapeutic variations and disease outcomes. Acknowledgements Funding for this study was provided by CORRONA (study sponsor), from a development and subscription agreement/contract with AstraZeneca. Disclosure of Interest D. Pappas Employee of: Columbia University, Paid instructor for: Novartis, K. Lampl Employee of: AstraZeneca, J. Kremer Shareholder of: CORRONA, Inc., Employee of: CORRONA, Inc., F. Nyberg Employee of: AstraZeneca, A. Gibofsky Consultant for: AstraZeneca, M. Ho Employee of: AstraZeneca, L. Horne Shareholder of: AstraZeneca, Employee of: AstraZeneca, K. Saunders Employee of: CORRONA, Inc., A. Onofrei Employee of: University of Massachusetts, J. Greenberg Shareholder of: CORRONA, Inc., Consultant for: AstraZeneca, CORRONA, Novartis, Pfizer

Prevalence of cardiovascular disease and major risk factors in patients with rheumatoid arthritis: a multinational cross-sectional study

To compare the prevalence of cardiovascular disease (CVD) and major CVD risk factors among rheumatoid arthritis (RA) patients enrolled in a large US and multinational registry. We compared CVD and CVD risk factor prevalence from 11 countries enrolled in the CORRONA US and CORRONA International registries; patients from the 10 ex-US participating countries were grouped by region (Eastern Europe, Latin America, and India). Unadjusted summary data were presented for demographics and disease characteristics; comparisons for prevalence of CVD risk factors and CVD were age/gender standardized to the age/gender distribution of the US enrolled patients. Overall, 25,987 patients were included in this analysis. Compared to patients from the ex-US regions, US participants had longer disease duration and lower disease activity, yet were more likely to receive a biologic agent. Additionally, CORRONA US participants had the highest body mass index (BMI). Enrolled patients in India had the lowest BMI, were more rarely smokers, and had a low prevalence of hyperlipidemia, hypertension, and prior CVD compared to the US and other ex-US regions. Participants from Eastern Europe had a higher prevalence of hypertension and hyperlipidemia and highest prevalence of all manifestations of CVD. Differences in the prevalence of both CVD and major CVD risk factors were observed across the four regions investigated. Observed differences may be influenced by variations in both non-modifiable/modifiable characteristics of patient populations, and may contribute to heterogeneity on the observed safety of investigational and approved therapies in studies involving RA patients from different origins.

FRI0184 A Snapshot of Contemporary Urate-Lowering Therapy (ULT) Care and Serum Uric Acid (SUA) Monitoring in A US Commercially-Insured Gout Population

Background Gout is the most common inflammatory arthritis in most western countries and is caused by hyperuricemia. The reduction of gout symptoms, as well as the reduction and maintenance of sUA levels ≤6 mg/dL, is a commonly recommended treatment goal for gout patients. Objectives To provide a snapshot of contemporary ULT care, sUA monitoring, and associated costs in the US commercially-insured gout population. Methods Gout patients treated with ULT were identified between 1 Feb 2011 and 31 Jan 2012 from the HealthCore Integrated Research Environment. The index event was considered to be the earliest of the following events: a prescription for ULT, a diagnosis of gout (ICD-9 274.xx), or a claim for colchicine with ULT therapy in the year prior. Patients with <12 months pre- and post-index enrolment or with a diagnosis of cancer were excluded. Patient demographics and comorbidities were captured in the 12 month pre-index period. Treatment characteristics, sUA laboratory tests, overall gout control (defined as: sUA ≤6 mg/dL, no flares, and no tophi), and costs were examined during the 12 month post-index period. Flares were defined during the post-index period as either a claim for colchicine, or a healthcare visit recording gout together with at least one of the following treatment patterns within 1 week: joint aspiration or injection (corticosteroids), prescription of NSAIDs, corticosteroids, adrenocorticotropic hormone, or IL-1 antagonist. Results 50,602 ULT-treated patients met the inclusion criteria, including 29% new ULT users. The average age was 59, and 82% were male. During follow-up, 90% of patients received allopurinol, 6% received febuxostat, and 4% received probenecid. Comorbidities were common, including hypertension (70% of patients), hyperlipidemia (61%), and diabetes (30%). Most patients had prior ULT use (71%), while the rest initiated ULT treatment on the index date. Use of acute gout care drugs consisted of colchicine (18%), NSAIDs (32%), and corticosteroids (22%). Overall, 46% of patients had at least 1 sUA laboratory test during the one-year follow-up period. Within the subset of patients with available sUA results (n=6,649), 47% of subjects had sUA levels ≤6 mg/dL and 30% had achieved overall gout control. For the overall study population, average all-cause costs were

Comorbidity Burden in Trial-Aligned Patients with Established Gout in Germany, UK, US, and France: a Retrospective Analysis.

11,804. Those with 0 flares had the lowest average all-cause costs (