Abstract Tumor-induced Osteomalacia (TIO) and Epidermal Nevus Syndrome with osteomalacia (ENS) are rare conditions in which ectopic production of FGF23 by tumor (TIO) and bone (ENS) lead to renal phosphate wasting, impaired 1,25(OH)2D synthesis, osteomalacia, fractures, weakness, fatigue and decreased mobility. In an ongoing open-label Phase 2 study (NCT02304367), 17 adults were enrolled and treated with burosumab, a fully human monoclonal antibody against FGF23. Key endpoints were change in serum phosphorus and osteomalacia as assessed from trans-iliac crest bone biopsies. The per protocol (PP) analysis included 14/17 subjects who received 0.3-2.0 mg/kg burosumab every 4 weeks (W). Three subjects were excluded: 1 received subthreshold dosing (0.3 mg/kg at Day 0 and 0.15 mg/kg at W8, W32, and W72); 2 were diagnosed with X-linked hypophosphatemia post-enrollment. Ten subjects in the PP group had paired bone biopsies at baseline and W48. Mean ± SE histomorphometric values for the 8/10 subjects with osteomalacia at baseline were 20.4 ± 4.2 µm for osteoid thickness (OT), 23.0 ± 7.2% for osteoid volume/bone volume (OV/BV), and 66.1 ± 10.6% for osteoid surface/bone surface (OS/BS); baseline median (Q1, Q3) for mineralization lag time (MLT) was 1672 (1102, 2929) days. At W48, histomorphometric indices improved as shown by mean percentage changes in OT (37%), OV/BV (40%), OS/BS (-5%), and MLT (median percentage change -78%). Serum phosphorus, fatigue, and physical functioning are reported for the PP group. Mean (SD) serum phosphorus was 1.5 (0.3) mg/dL at baseline and 2.6 (0.8) mg/dL when averaged across the mid-point of the dose interval through W24. After W24, serum phosphorus, assessed only at the end of the dose interval, maintained this increase through W72. Mean (SD) Global Fatigue Score decreased from 5.3 (2.8) at baseline to 3.6 (2.9) at W48 (p=0.020) and to 3.3 (2.7) at W72 (p=0.004). The SF-36 mean (SD) physical component summary score increased from 34 (11) at baseline to 39 (10) at W48 (p=0.059) and to 42 (10) at W72 (p=0.003). Mean (SD) vitality score increased from 41 (14) to 47 (12) at W48 (p=0.075) and to 49 (12) at W72 (p=0.012). The mean (SD) number of sit-to-stand repetitions increased from 6.9 (4.0) at baseline to 8.6 (4.2) at W48 (n=10; p=0.004). By W72, all 17 subjects had ≥1 adverse event (AE). There were 13 serious AEs in 6 subjects, none were considered drug-related. Tumor progression occurred only in subjects with a history of tumor progression prior to enrollment. One subject discontinued treatment prior to W48 to treat tumor progression with chemotherapy. There was 1 death, considered unrelated to treatment. In adults with TIO Syndrome, burosumab was associated with improvements in serum phosphorus, osteomalacia, mobility, quality of life, and reductions in fatigue.

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.

Safety concerns associated with many drugs indicated for the treatment of rheumatoid arthritis (RA) can be attenuated by the early identification of toxicity through routine laboratory monitoring; however, a comprehensive review of the recommended monitoring guidelines for the different available RA therapies is currently unavailable. The aim of this review is to summarize the current guidelines for laboratory monitoring in patients with RA and to provide an overview of the laboratory abnormality profiles associated with each drug indicated for RA. Recommendations for the frequency of laboratory monitoring of serum lipids, liver transaminases, serum creatinine, neutrophil counts, and platelet counts in patients with RA were compiled from a literature search for published recommendations and guidelines as well as the prescribing information for each drug. Laboratory abnormality profiles for each drug were compiled from the prescribing information for each drug and a literature search including meta-analyses and primary clinical trials data.

Background Two previous randomized, controlled trials (RCTs), BREVACTA and SUMMACTA, showed subcutaneous tocilizumab (TCZ-SC) was superior to placebo (PBO) and comparable to intravenous TCZ (TCZ-IV) in combination with csDMARDs for improving RA disease activity.1,2 Objectives To compare the efficacy of TCZ-SC with PBO or TCZ-IV + csDMARDs for improvement in patient-reported outcomes (PROs) in 2 RCT populations. Methods Both RCTs enrolled patients (pts) with inadequate responses to DMARDs; up to 20% had inadequate responses to tumor necrosis factor inhibitors. In BREVACTA, pts received blinded TCZ-SC 162 mg or PBO every 2 weeks (q2w) + csDMARDs for 24 weeks. In SUMMACTA, pts received TCZ-SC 162 mg weekly or TCZ-IV 8 mg/kg q4w + csDMARDs for the 24-week double-blind period. PROs, assessed at 12 weeks (prior to rescue) in BREVACTA and 24 weeks in SUMMACTA, included patient global assessment (PtGA; visual analog score [VAS], 0–100 mm), pain (VAS), Health Assessment Questionnaire Disability Index (HAQ-DI, 0–3) and Short Form-36 (SF-36) physical and mental component summary (PCS, MCS: 0–50) and domain (0–100) scores. The proportions of pts reporting scores ≥ minimum clinically important differences (MCID) and ≥ age/gender-matched normative values were assessed for each treatment group. Results Baseline PRO scores were mostly comparable between treatment groups in each study and between study populations. In BREVACTA, significantly more pts who received TCZ-SC reported scores ≥ MCID for all PROs at week 12 compared with PBO (54% to 73% vs 42% to 55%, respectively; number needed to treat [NNT], 5.2 to 13.0). Compared with 1% to 20% at baseline, 8% to 34% of pts who received TCZ-SC and 4% to 25% of PBO pts reported scores ≥ normative values in all PROs at week 12 (Table). In SUMMACTA, similar proportions of pts who received TCZ-SC and TCZ-IV reported scores ≥ MCID in all PROs at week 24 (61% to 84% vs 64% to 84%, respectively). The proportion of patients who reported scores ≥ normative values was comparable between the TCZ-SC and TCZ-IV groups across all PROs; compared with 0.2% to 23% at baseline, 14% to 41% of pts who received TCZ-SC and 15% to 42% of pts who received TCZ-IV reported scores ≥ normative values at week 24 (Table). Conclusions In BREVACTA, TCZ-SC + csDMARDs resulted in significantly greater improvements across all PROs and significantly more pts reporting scores ≥ MCID at week 12 compared with PBO. Similarly, more pts receiving TCZ-SC reported scores ≥ normative values at week 12 compared with PBO, despite few pts with such scores at baseline. Responses were similar between pts treated with TCZ-SC and TCZ-IV + csDMARDs in SUMMACTA at week 24. These data show TCZ treatment resulted in clinically meaningful improvements in PROs and indicate that attainment of normative scores is a realistic goal in treatment of pts with active RA. References Kivitz A, et al. Arthritis Care Res (Hoboken). 2014;66:1653–61. Burmester G, et al. Ann Rheum Dis. 2014;73:69–74. Acknowledgements This study was funded by F. Hoffmann-La Roche/Genentech. Disclosure of Interest V. Strand Consultant for: Abbvie; Amgen; AstraZeneca; Biogen Idec; Boehringer Ingelheim; Celltrion; Crescendo; Genentech/Roche; GlaxoSmithKline; Janssen; Lilly; Merck; Novartis; Pfizer; Regeneron; Samsung; Sanofi; UCB, K. Lampl Employee of: Genentech, Inc, C. Birchwood Employee of: Genentech, Inc, J. Pei Employee of: Genentech, Inc, K. Tuckwell Shareholder of: Roche, Employee of: Roche, R. Finch Shareholder of: Roche, Employee of: Roche, A. Kivitz Consultant for: Genentech; Novartis; Pfizer; Sanofi-Regeneron; UCB, G. Burmester Grant/research support from: Roche, Consultant for: Roche

The aim of this study was to use multiple data sources to update information on gastrointestinal perforations (GIPs) during tocilizumab (TCZ) treatment in patients with rheumatoid arthritis (RA).

Objective 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. Methods Using predefined definitions, 2 subsets of patients (main cohort and subcohort) from 5 international observational registries (Consortium of Rheumatology Researchers of North America Registry [CORRONA], the Swedish Rheumatology Quality of Care Register [SRR], the Norfolk Arthritis Register [NOAR], the Institute of Rheumatology Rheumatoid Arthritis cohort [IORRA], and CORRONA International) were evaluated and compared. Patients ages >18 years with RA, and present in or recruited to the registry from January 1, 2000, were included in the main cohort. Patients from the main cohort with positive rheumatoid factor and/or erosive RA who had received ≥1 synthetic disease‐modifying antirheumatic drug (DMARD), and switched to or added another DMARD, were included in the subcohort at time of treatment switch. Results Age and sex distributions were fairly similar across the registries. The percentage of patients with a high Disease Activity Score in 28 joints score varied between main cohorts (17.5% IORRA, 18.9% CORRONA, 24.7% NOAR, 27.7% CORRONA International, and 36.8% SRR), with IORRA, CORRONA, and CORRONA International including more prevalent cases of RA; the differences were smaller for the subcohort. Prevalence of comorbidities varied across registries (e.g., coronary artery disease ranged from 1.5% in IORRA to 7.9% in SRR), partly due to the way comorbidity data were captured and general cultural differences; the pattern was similar for the subcohorts. Conclusion Despite different inclusion criteria for the individual RA registries, it is possible to improve the comparability and interpretability of differences across RA registries by applying well‐defined cohort definitions.

Background Cardiovascular disease (CVD) is a major comorbidity in patients (pts) with rheumatoid arthritis (RA). We explored variations in the prevalence of cardiovascular (CV) risk factors and CVD among RA pts in different international regions using data from CORRONA International (C.Intl) and CORRONA US (C.USA) RA registries. Methods The C.Intl registry is a multi-center, observational registry. Adult RA pts have been enrolled from 83 rheumatology practices in 10 countries in 3 regions - Latin America (Mexico, Brazil, Argentina), Eastern Europe (Poland, Czech Republic, Hungary, Romania, Russia, Ukraine), Asia (India). The C.USA registry enrolls pts from 111 rheumatology practices across the United States. Both registries collect data in a similar manner from rheumatologists and RA pts at regular clinical encounters. We compared cross-sectional baseline descriptive C.Intl data for demographic and disease characteristics with cross-sectional data from the most recent visit of C.USA-enrolled pts. Prevalence for CV risk factors and CVD are presented crude for C.USA and age/gender-standardized to the C.USA age/gender distribution (age categories <50, 50-<60, 60-<70, ≥70 years) for C.Intl regions. Results We analyzed 5696 pts enrolled in C.Intl and 20291 pts actively followed in C.USA. While there are cross-sectional differences across all regions, the greatest differences are between the US and C.Intl regions overall. There is a higher percentage of male pts in C.USA, disease duration is longer, and pts tend to have lower disease activity, yet are more likely to receive a biologic (Table 1). After adjusting for age and gender differences by standardization, enrolled pts in India have the lowest BMI, are more rarely smokers and have a low prevalence of hyperlipidemia and CVD compared to other C.Intl regions and C.USA (Table 1). C.USA participants have the highest BMI. Participants from Eastern Europe suffer more frequently from hypertension and hyperlipidemia and have the highest prevalence of all manifestations of CVD (Table 1). Conclusions Data from the C.Intl and C.USA registries reveal variations in disease characteristics, as well as prevalence of CV risk factors and CVD, across different regions. Observed variations may be influenced by differences in the composition and treatment of pts populations, and this should be considered in analyses and evaluation of pts from different geographic origins. Acknowledgements This study is sponsored by CORRONA. Initial funding for the CORRONA International was provided by AstraZeneca. In the last two years, AbbVie, Amgen, AstraZeneca, Genentech, Horizon Pharma, Lilly, Novartis, Pfizer, Savient, Vertex, and UCB have supported CORRONA through contracted subscriptions. Disclosure of Interest D. Pappas Employee of: CORRONA, Inc., Paid instructor for: Novartis, K. Lampl Shareholder of: AstraZeneca, Employee of: AstraZeneca, J. Kremer Shareholder of: CORRONA, Inc., Employee of: CORRONA, Inc., S. Radominski Consultant for: Pfizer, BMS, AstraZeneca, Employee of: Universidade Federal do Parana- Curitiba- Brazil;, Speakers bureau: Pfizer,BMS,AstraZeneca,Janssen,Sanofi, GSK, J. Gal: None declared, F. Nyberg Shareholder of: AstraZeneca, Employee of: AstraZeneca, A. Malaviya Consultant for: Part-time Consultant Rheumatologist at ISIC Hospital, Advisory Board Member Janssen Pharma, Roche Pharma, Pfizer Pharma, Sanofi Pharma, A. Whitworth Employee of: CORRONA, Inc., O. Rillo: None declared, A. Gibofsky Shareholder of: Amgen, BMS, GlaxoSmithKline, Johnson&Johnson, Pfizer, Roche, Consultant for: Amgen, AstraZeneca, Celgene, Horizon, Iroko, Pfizer, Roche, Antares, UCB, Speakers bureau: Amgen, Pfizer, Roche, UCB, T. Popkova Speakers bureau: GlaxoSmithKline, MSD, AstraZeneca, M. Ho Employee of: AstraZeneca, I. Laurindo Consultant for: Abbott, AstraZeneca, Bristol,Janssen,Pfizer, Speakers bureau: Abbott, AstraZeneca, Bristol,Janssen,Pfizer, Roche, G. Reed Employee of: CORRONA, Inc., E. Kerzberg: None declared, L. Horne Shareholder of: AstraZeneca, Employee of: AstraZeneca, R. Zahora: None declared, K. Saunders Employee of: CORRONA, Inc., B. Pons-Estel Grant/research support: GLADAR, Abbott Laboratories, A. Onofrei Employee of: UMASS Medical School, J. Greenberg Shareholder of: CORRONA, Inc., Consultant for: AstraZeneca, Pfizer, Employee of: CORRONA, Inc. DOI 10.1136/annrheumdis-2014-eular.1695

Objective. Our 24-week study (NCT01197755; OSKIRA-3) compared the efficacy and safety of fostamatinib versus placebo in patients taking background methotrexate treatment with active rheumatoid arthritis (RA) and an inadequate response to a single tumor necrosis factor-α antagonist. Methods. Adult patients were randomized (1:1:1) to fostamatinib [100 mg bid for 24 weeks (n = 105; Group A)], or 100 mg bid for 4 weeks, then 150 mg qd (n = 108; Group B), or to placebo (n = 110; Group C) for 24 weeks. Nonresponders at Week 12 could enter a longterm extension study. The primary endpoint was the proportion of patients achieving an American College of Rheumatology 20% (ACR20) response at Week 24. Results. Baseline characteristics were well balanced. Significantly more patients in fostamatinib Group A (36.2%; p = 0.004), but not B (27.8%; p = 0.168), achieved ACR20 at Week 24 versus placebo (21.1%). Frequently reported adverse events were diarrhea, hypertension, and headache. Elevated blood pressure (≥ 140/90 mm Hg) at ≥ 1 visit was observed in 46.7%, 51.9%, and 26.6% of patients, respectively. There were 2 deaths in the study, 1 in Group B and 1 in the placebo group. Conclusion. Fostamatinib 100 mg bid, but not fostamatinib 100 mg bid for 4 weeks then 150 mg qd, achieved statistical improvements in ACR20 at 24 weeks versus placebo. Because of efficacy and safety results from the phase III clinical program, the companies developing fostamatinib have decided not to study it further in RA at this time.

Background The CORRONA International (C.Intl) rheumatoid arthritis (RA) registry is a multinational RA registry uniformly collecting baseline and longitudinal data. We explored variations in RA disease activity and drug utilization across regions participating in C.Intl, and CORRONA US (C.USA) RA registries. Methods The C.Intl registry is a multi-center, observational registry. Adult RA patients (pts) have been enrolled from 83 rheumatology practices in 10 countries in 3 regions: Latin America (LA) (Mexico, Brazil, Argentina), Eastern Europe (EEu) (Poland, Czech Republic, Hungary, Romania, Russia, Ukraine), Asia (India). The C.USA registry enrolls pts from 111 rheumatology practices across the US. Both registries collect data in a similar manner from rheumatologists and RA pts. We present baseline descriptive data across the regions participating in C.Intl, including variations in RA drug utilization, disease activity and functionality. We explored differences stratified by new (≤3 years duration) versus established (3+ years) disease. We compared C.Intl data by region with data from the most recent visit of pts enrolled in C.USA. Results 5696 pts enrolled in C.Intl and 20,291 RA pts followed in C.USA were analyzed. Mean (Standard Deviation (SD)) age was highest in the US and lowest in Asia [LA 54.2 years (12.9), EEu 57.1 (12.2), Asia 47.6 (11.9), US 60.3 (12.6)]. The majority of patients were women (LA: 86.7%, EEu: 83.4%, Asia: 85.5%, US: 76.6%). Mean (SD) disease duration was indicative of overall established dx [LA 9.9 years (8.7), EEu 9.1 (8.6), Asia 6.3 (5.8), US 12 (10.1)]. The majority of pts were seropositive (LA 83.5%, EEu 76.4%, Asia 65.4%, US 76%). Disease activity was higher, functionality worse, but biologic drug utilization and narcotic pain medication use were lower, in C.Intl regions compared to C.USA (Table 1). Conclusions There are regional differences in disease activity, functionality, and management of RA, which may be influenced by variations in demographic and genetic backgrounds of pt populations, prescribing patterns of local physicians and differences in standard of care. Acknowledgements This study is sponsored by CORRONA. Initial funding for the CORRONA International was provided by AstraZeneca. In the last two years, AbbVie, Amgen, AstraZeneca, Genentech, Horizon Pharma, Lilly, Novartis, Pfizer, Savient, Vertex, and UCB have supported CORRONA through contracted subscriptions. Disclosure of Interest D. Pappas Employee of: CORRONA, Inc., Paid instructor for: Novartis, K. Lampl Shareholder of: AstraZeneca, Employee of: AstraZeneca, J. Kremer Shareholder of: CORRONA, Inc., Employee of: CORRONA, Inc., S. Radominski Grant/research support: Pfizer,BMS,AstraZeneca, Amgen, Sanofi, Novartis, Celltrion, Roche;, Consultant for: Pfizer,BMS,AstraZeneca, Employee of: Universidade Federal do Parana- Curitiba- Brzazil;, Speakers bureau: Pfizer,BMS,AstraZeneca,Janssen,Sanofi, GSK, J. Gal: None declared, F. Nyberg Shareholder of: AstraZeneca, Employee of: AstraZeneca, A. Malaviya Consultant for: Part-time Consultant Rheumatologist at ISIC Hospital, Advisory Board Member Janssen Pharma, Roche Pharma, Pfizer Pharma, Sanofi Pharma, A. Whitworth Employee of: CORRONA, Inc., O. Rillo: None declared, A. Gibofsky Shareholder of: Amgen, BMS, GlaxoSmithKline, Johnson & Johnson, Pfizer, Roche, Consultant for: Amgen, AstraZeneca, Celgene, Horizon, Iroko, Pfizer, Roche, Antares, UCB, Speakers bureau: Amgen, Pfizer, Roche, UCB; Stockholder, T. Popkova Speakers bureau: GlaxoSmithKline, MSD, AstraZeneca, M. Ho Employee of: AstraZeneca, I. Laurindo Consultant for: Abbott,AstraZeneca, Bristol, Janssen, Pfizer, Speakers bureau: Abbott, AstraZeneca, Bristol, Janssen, Pfizer, Roche, G. Reed Employee of: CORRONA, Inc., E. Kerzberg: None declared, L. Horne Shareholder of: AstraZeneca, Employee of: AstraZeneca, R. Zahora: None declared, K. Saunders Employee of: CORRONA, Inc., B. Pons-Estel Grant/research support: GLADAR, ABBOTT Laboratories, A. Onofrei Employee of: UMASS Medical School, J. Greenberg Shareholder of: CORRONA, Inc., Consultant for: AstraZeneca, Pfizer, Employee of: CORRONA, Inc. DOI 10.1136/annrheumdis-2014-eular.1692

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