BackgroundImmune checkpoint inhibitors targeting cytotoxic T-lymphocyte-associated protein 4 and programmed cell death protein 1 (PD-1) have been established as a novel standard treatment for various types of malignancies. However, these new class of drugs have led to increased immune-related adverse events (IrAEs) including rheumatic manifestations.ObjectivesTo determine the risk factors of IrAEs in patients treated with anti-PD 1 antibody pembrolizumab.MethodsA retrospective medical record review was performed to identify all patients who received at least one dose of pembrolizumab at Samsung Medical Centre, Seoul, Korea between June 2015 and December 2017. Three hundred and ninety two patients were identified. Multivariate logistic regression model was used to identify risk factors of IrAEs.ResultsThe mean age was 59.7±13.0 years (range, 18–95) and the median number of doses of pembrolizumab was 2 (IQR, 1.25–5). The primary malignancies included in the study were lung cancer (n=212, 54.1%), melanoma (n=74, 18.9%), lymphoma (n=53, 13.5%) and others (n=53, 13.5%). Sixty-seven (17.1%) patients experienced clinically significant IrAEs; most commonly dermatologic disorders (n=39, 9.9%), pneumonitis (n=11, 2.8%), musculoskeletal disorders (n=10, 2.6%), followed by endocrine disorders (n=7, 1.8%). Fourteen patients (3.6%) experienced serious IrAEs (≥Grade 3). Most common serious IrAEs were pneumonitis (n=9, 2.3%). There were 4 deaths associated with IrAEs, all of which were due to pneumonitis. Multivariate logistic regression analysis showed that obesity was the risk factors of IrAEs in pembrolizumab-treated patients. Patients with a body mass index (BMI) of 25 or higher had a 3.65-fold higher risk of IrAEs compared with patients with a BMI between 18.5 and 22.9 (95% CI, 1.58 to 8.42).ConclusionsTo our knowledge, this is the first study to explore the risk factor for IrAE in patients undergoing modern cancer immunotherapy. Our study demonstrate that BMI is associated with an increased risk of IrAEs in patients treated with pembrolizumab. Further studies to investigate the potential mechanisms by which obesity raises IRAEs are needed.Disclosure of InterestNone declared

Background The role of serum uric acid as an independent risk factor for cardiovascular disease (CVD) remains unclear, although hyperuricemia is associated with CVD such as ischemic heart diseases (IHD), cerebrovascular accidents (CVA), or peripheral arterial occlusive diseases (PAOD). In particular, no study showed long-term cumulative effect of serum uric acid on CVD in gout patients with treatment. Objectives The aim of this study is to evaluate long-term cumulative effect of serum uric acid on CVD and determine predictive factors of CVD in gout patient with uric acid lowering treatment. Methods All patients who had a first visit for gout at Samsung Medical Center between 1995 and 2003, and follow-up until December 2012 or expired during follow-up period were included and retrospective analyzed. Cox regression according to level of control of uric acid defined as time-dependent covariate of each uric acid level and the ratio of numbers of uric acid level more than 6 umol/l to total numbers of measured uric acid level was performed to assess the effect of long-term cumulative uric acid level on CVD in gout patients with treatment. Results Three-hundred twenty seven patients with gout were observed. Mean age at diagnosis of gout was 45.7 and mean follow-up duration was 14.1 years. Of these, 67 (20.5%) patients developed CVD during follow-up period, which included 34 IHD, 28 CVA, and 5 PAOD. CVD related death was observed in 10 patients (3.1%). Mean duration of gout at diagnosis of CVD was 13.3 years. For every 1 umol/l increase of uric acid level, the risk of CVD revealed to be increased 1.32-fold after adjusting age, smoking, family history of premature CVD, obesity, chronic kidney disease, time-dependent diabetes mellitus, hypertension, and hyperlipidemia (adjusted HR 1.32 (1.17-1.48), p<0.0001). In particular, the patients who had high proportion of events of uric acid over 6 umol/l was associated with increased CVD risk (adjusted HR 3.82 (1.08-13.56), p=0.037). Subgroup analysis by Cox regression showed that time-dependent uric acid level is related to increase the risk of IHD and severe CVD (adjusted HR 1.42 (1.23-1.64) p<0.001 and adjusted HR 1.33 (1.77- 1.33 (1.17-1.50), p<0.0001, respectively). Age at diagnosis of gout, family history of premature CVD, and diabetes mellitus were significantly associated with increased risk of CVD (adjusted HR 1.11 (1.02-1.06), p<0.0001, 13.30 (7.52-23.52), p<0.0001, and 2.65 (1.35-5.18), p=0.005, respectively). Conclusions Our data demonstrated serum uric acid level was associated with increased risk of CVD in gout patients with treatment, which is a first data determined the long-term cumulative effect of uric acid on CVD. To control hyperuricemia is important to prevent CVD beyond gout itself in patients with gout. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4817

BackgroundThe international Chapel Hill Consensus Conference (CHCC) categorised Behçet’s disease (BD) as variable vessel vasculitis, which was defined as vasculitis that can affect vessels of any size and type. Vascular manifestations have been reported in up to 50% of patients with BD, most commonly as venous thrombosis.ObjectivesThe aim of this study is to investigate characteristics and treatment outcomes of patients with vascular BD, particularly with large vessel involvement.MethodsA retrospective review was performed on 2496 patients with ICD-10 code of Behçet’s disease and/or aortic disease who visited Samsung Medical Centre between 2004 and 2014. Patients who were suspected to have BD and vascular involvement were enrolled.ResultsEighty-three patients with clinical features of BD and vascular involvement were identified. Although less than half satisfied the classic International Study Group (ISG) criteria, greater proportion fulfilled the International Criteria for BD (ICBD), and all of the patients satisfied at least “suspected BD” according to the Japanese criteria. Fifty patients had arterial lesions including 34 with aorta involvement. Another 33 patients had venous thrombosis without arterial lesions. Patients showed a male predominance (87%) and a predilection of young age with the median of 42 years old. The most prominent type of arterial lesions was aneurysm (80%) with a high frequency of pseudoaneurysms. Among the aorta, the thoracic aorta was most commonly involved and 18 patients had aortic valve regurgitation. Seventy-five (90%) patients received glucocorticoids with a median initial dose of prednisolone of 30 mg per day and 68 (82%) received immunosuppressive treatment. Half of the patients had more than one relapse after stabilisation of the first vascular event. During the course, 44 patients underwent surgery and/or endovascular treatment and 60% of these patients had repeated treatment for the relapse. These included 31 aortic valve replacements on 13 patients.ConclusionsPatients with vascular BD showed a predilection of young male and 60% of patients had arterial involvement. The aorta was affected in more than half of the patients who had arterial involvement. Aneurysmal change was frequent finding and relapse rate was high during disease course. Further studies into a practical and specialised diagnostic tool for vascular BD and optimal treatment strategies are required.Disclosure of InterestNone declared