tbuckley/cabot-search huggingface dataset:
Phase 2 results: Encorafenib (ENCO) and cetuximab (CETUX) with or without alpelisib (ALP) in patients with advanced <i>BRAF-</i>mutant colorectal cancer (<i>BRAFm</i> CRC).
Authors: Josep Tabernero, Robin Van Geel, Tormod Kyrre Guren, Rona D. Yaeger, Anna Spreafico, Jason Edward Faris, Takayuki Yoshino, Yasuhide Yamada, Tae Won Kim, Johanna C. Bendell, Martin H. Schuler, Heinz-Josef Lenz, Ferry Eskens, Jayesh Desai, Howard S. Hochster, Emin Avsar, Tim Demuth, Victor Sandor, Elena Elez, Jan H.M. Schellens
Journal: Journal of Clinical Oncology (2016)

3544 Background: BRAFm CRC carries a poor prognosis, with survival of 5–6 months after failure of first-line therapy. Reactivation of epidermal growth factor receptor (EGFR) signaling with BRAF inhibition and uninhibited PI3K signaling may explain the limited efficacy of BRAF inhibitor monotherapy in patients (pts) with BRAFm CRC. This study investigated the BRAF inhibitor ENCO and the anti-EGFR antibody CETUX with or without the PI3Kα inhibitor ALP (BYL719) in pts with advanced BRAFm CRC. Methods: In this ongoing phase 1b/randomized phase 2 study (ClinicalTrials.gov: NCT01719380), phase 1b did not identify a maximum tolerated dose for either combination. Based on general tolerability of the triplet, the ENCO dose for phase 2 was chosen to be the same in both arms. In phase 2, pts with advanced BRAFm CRC failing ≥ 1 prior therapy were randomized 1:1 to a doublet (ENCO 200 mg PO QD and CETUX per label) or triplet (ENCO, CETUX, and ALP 300 mg PO QD). Progression-free survival (PFS) was the primary endpoint. Secondary endpoints included overall response rate (ORR) and overall survival (OS). Results: A total of 102 pts were randomized (triplet, n = 52; doublet, n = 50). Pts in each group had a median of 2 prior therapies. A planned PFS analysis comparing the triplet to the doublet after 73 events showed a HR (95% CI) of 0.69 (0.43–1.11; P= 0.064) with median PFS (95% CI) of 5.4 (4.1–7.2) mo and 4.2 (3.4–5.4) mo and confirmed ORR (95% CI) of 27% (16%–41%) and 22% (12%–36%), respectively. With 35 events, interim OS analysis (triplet vs doublet) showed a HR (95% CI) of 1.21 (0.61–2.39); median OS was 15.2 mo on the triplet and not reached on the doublet. Grade 3/4 adverse events (AEs), regardless of causality, were reported in 79% (triplet) and 58% (doublet) of pts. Grade 3/4 AEs in > 10% of pts in either arm were anemia (17% vs 6%), hyperglycemia (13% vs 2%), and increased lipase (8% vs 18%) for the triplet and doublet, respectively. Conclusions: Combinations of ENCO and CETUX with or without ALP showed promising clinical activity, including improved PFS and OS relative to historical data. Adding ALP to the doublet may add a PFS benefit as well as additional toxicity. Clinical trial information: NCT01719380.
THU0765-HPR Patient satisfaction and self-monitoring of chronic inflammatory arthritis
Authors: K Grønning, EK Lyngvær, AS Magnussen, E Rødevand
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Effective drug treatment for patients with inflammatory arthritis have brought a major proportion of patients in clinical remission. The need for regular follow-up intervals in specialized care is less; patients take greater responsibility for their own care, and patients request access to more flexible health care services. As a result of this development, the University Hospital, St.Olavs Hospital, Department of Rheumatology, has developed a on-demand pathway (PORS) for patients with inflammatory arthritis (RA, PsA and AS) in clinical remission or low disease-activity aiming for increased patient responsibility and flexibility. <h3>Objectives</h3> The aim of this study was to investigate patients9 satisfaction with PORS regarding disease status, treatment, knowledge, responsibility, and cooperation with health care professionals. <h3>Methods</h3> We conducted a quest-back survey for patients included in PORS for ≥1 year in the period from June 2016 to October 2016. The survey contained 10 questions about the pathway. The response alternatives and scoring were: not at all =1, to a small extent =2, to some extent =3, to a large extent =4, to a very large extent =5, and not relevant =0. <h3>Results</h3> We identified 1048 eligible patients, 10 invitations were returned (unknown address), and 312 responded (30%). The descriptive analyses (see table) showed that the patients in general considered their disease activity to be in a stable phase. The cooperation with their general practitioner was good, they had to some or large extent sufficient knowledge to take responsibility for the blood test controls and adhere to prescribed medication. The patients were to some extent satisfied with the renewals of prescriptions and access to health professionals. The patients were less satisfied with the "promise" of getting outpatient appointments within 14 days if needed. Finally, the patients would largely recommend PORS to other patients. <h3>Conclusions</h3> We found that patients with inflammatory arthritis in general were satisfied with a management pathway encouraging greater responsibility for managing their own care and the possibility for more flexible contacts with the health care services. However, fullfilling the promise of outpatient appointments within 14 days were not always possible to achieve. <h3>Acknowledgements</h3> We would like to thank the local Rheumatology fund for financing the project. <h3>Disclosure of Interest</h3> None declared
Notes from the Field:<i>Vibrio cholerae</i>Serogroup O1, Serotype Inaba — Minnesota, August 2016
Authors: Victoria Hall, Carlota Medus, George Wahl, Alida Sorenson, Melanie Orth, Monica Santovenia, Erin Burdette, Kirk Smith
Journal: MMWR Morbidity and Mortality Weekly Report (2017)
AB0418 Comparison of anti-inflammatory drugs with glucocorticoids in treatment of rheumatoid arthritis
Authors: BN Coskun, F Ulutaş, S Ermurat, E Dalkılıc
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronical autoimmune disease that commonly presented with symmetrical polyarthritis of hands and feet. Pharmacological treatment options are non-steroid anti-inflammatory drugs (NSAIDs), glucocorticoids (GK) and disease modifying anti rheumatoid drugs (DMARDs) ([csDMARDs] or [tsDMARDs or [bDMARD]. <h3>Objectives</h3> In this study we aimed to review the use of NSAID and GK in our patients. <h3>Methods</h3> The patients who diagnosed as RA at our office were included in the study. Patients were classified with EULAR 2010 RA criteria. The demographics and medications of the patients were recorded. All patients we examined pain with visual analog scale (VAS), global assessment of patient and doctor, number of tender and swollen joints (28 joints), health assessment questionnaire (HAQ), C – reactive protein (CRP), eritrocyte sedimentation rate (ESR), rheumatoid factor (RF) and anti – CCP. We assessed activity of disease by using disease activity score DAS28. <h3>Results</h3> A total of 686 patients were enrolled in the study (580 female [84.5%], 106 male [15.5%]). Mean age was 53.23±12.21 and mean length of diagnosis was 10.74±7.59 months. The rate of extra-articular disease was 17.9% and the deformity rate was 31.3%. In all patients, activity of disease was mild in 55%, moderate in 37.8% and severe in 7.3% with regard to DAS28 score. The disease activity was mild in 54.6%, moderate in 43.11% and severe in 2.3% in patients who were using only NSAIDS. These rates of diseases activity was 57.2%, 40.7% and 2.1% in mild, moderate and severe disease respectively for the patients using only GK. In patients using both NSAIDs and GK, the disease activity was mild in 55%, moderate in 44% and severe in 1%. Comparison of the disease activity with medications revealed statistically significant difference in patients that using only NSAID and using both, but not in that using only steroid (respectively p: 0.022, p: 0.025, p: 0.46). <h3>Conclusions</h3> In our study we found that patients has mild activity of disease use highly rates of NSAID and GC. It is important for providing remission using NSAIDs and GC along with DMARD. Our results demonstrate use of both GK and NSAIDS results in better outcomes. <h3>References</h3> Singh JA, Saag KG, Bridges SL Jr et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol. 2016 Jan;68(1):1–26. Gaujoux-Viala C, Gossec L. When and for how long should glucocorticoids be used in rheumatoid arthritis? International guidelines and recommendations. Ann N Y Acad Sci. 2014 May; 1318:32–40. <h3>Acknowledgements</h3> None. <h3>Disclosure of Interest</h3> None declared
SP0055 What are the challenges for applying treat to target in axial spondyloarthritis?
Authors: M Dougados
Journal: Annals of the Rheumatic Diseases (2017)

The concept of Treat to Target (T2T) applied in rheumatoid arthritis has been evaluated in psoriatic arthritis and is currently under investigation in two different strategy trials in patients suffering from axial spondyloarthritis (axSpA). Whatever le results of these trials will be, the acceptation of this concept and consequently its implementation in daily practice might be challenging for several reasons. The concept of T2T necessitates 3 different steps and also the close collaboration of the patient and the availability of different treatment modalities. The three different steps consist in: a) the choice of the most relevant outcome measure (e.g. a measure evaluating a domain recognized as predisposing to subsequent clinically relevant damage (either structural damage or important comorbidities such as cardiovascular diseases)). b) the determination of the threshold of the outcome measure to reach (threshold below which the risk of subsequent damage is abolished or significantly decreased). c) The time to reach the target is usually related to the treatment modality (a few days for NSAIDs and several weeks for DMARDs). A part these different steps, two points have to be considered a) this T2T approach is impossible without embarking the patient in a true share decision b) this T2T strategy requires the possibility to adapt/increase the treatment in case the target is not reached after one or several "conventional" treatment modalities. For each of these different points we will consider past-on ongoing initiatives proposing to resolve the different encountered issues in order to facilitate the elaboration and the implementation of a T2T strategy in AxSpA. <h3>Disclosure of Interest</h3> M. Dougados Grant/research support from: UCB,ABBVIE,PFIZER,MERCK, Consultant for: UCB,ABBVIE,PFIZER,MERCK
Randomized Phase III Trial of Adjuvant Pazopanib Versus Placebo After Nephrectomy in Patients With Localized or Locally Advanced Renal Cell Carcinoma
Authors: Robert J. Motzer, Naomi B. Haas, Frede Donskov, Marine Gross-Goupil, Sergei Varlamov, Evgeny Kopyltsov, Jae Lyun Lee, Bohuslav Melichar, Brian I. Rini, Toni K. Choueiri, Milada Zemanova, Lori A. Wood, M. Neil Reaume, Arnulf Stenzl, Simon Chowdhury, Ho Yeong Lim, Ray McDermott, Agnieszka Michael, Weichao Bao, Marlene J. Carrasco-Alfonso, Paola Aimone, Maurizio Voi, Christian Doehn, Paul Russo, Cora N. Sternberg
Journal: Journal of Clinical Oncology (2017)

Purpose This phase III trial evaluated the efficacy and safety of pazopanib versus placebo in patients with locally advanced renal cell carcinoma (RCC) at high risk for relapse after nephrectomy. Patients and Methods A total of 1,538 patients with resected pT2 (high grade) or ≥ pT3, including N1, clear cell RCC were randomly assigned to pazopanib or placebo for 1 year; 403 patients received a starting dose of 800 mg or placebo. To address toxicity attrition, the 800-mg starting dose was lowered to 600 mg, and the primary end point analysis was changed to disease-free survival (DFS) for pazopanib 600 mg versus placebo (n = 1,135). Primary analysis was performed after 350 DFS events in the intent-to-treat (ITT) pazopanib 600 mg group (ITT
FRI0350 Investigating the link between ischemic heart disease and behcet's disease: a cross-sectional analysis
Authors: Y Yavne, S Tiosano, A Watad, D Comaneshter, AD Cohen, H Amital
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Behcet9s disease (BD) is a multi-systemic chronic inflammatory disorder which involves the vasculature tree of all sizes. Subclinical endothelial injury as a result of chronic inflammation in BD has been associated with thrombosis and arterial stiffness, risk factors for ischemic heart disease (IHD)<sup>1–4</sup>. However, data regarding the association between BD and IHD and the impact of various risk factors on this association, is scarce<sup>3–5</sup>. <h3>Objectives</h3> To examine the association between BD and the development of IHD and its potential impact as a cardiovascular risk factor. <h3>Methods</h3> This study was conducted as a case-control study utilizing the database of Clalit Health Services. The proportion of IHD was compared between patients diagnosed with BD and age- and gender-matched controls. Univariate analysis was performed using Chi-square and student <i>t-test</i> and a multivariate analysis was performed using a logistic regression model. <h3>Results</h3> 871 BD patients and 4,439 age- and gender-matched controls were included in this study. The proportion of IHD amongst BD patients was increased in comparison with controls (10.9% vs. 7.52% respectively, <i>p</i>-value =0.001). After controlling for cofounders, BD was associated with IHD on multivariate analysis (odds ratio 1.485, 95% confidence interval 1.106–1.982, Table 1). When the comparison between BD patients with IHD and controls with IHD was stratified according to risk factors, age younger than 70 and male gender were both found to be significantly elevated in the BD group. <h3>Conclusions</h3> BD patients have an increased proportion of IHD in comparison with matched controls. The population of BD patients with IHD has a higher proportion of younger males in comparison with controls with IHD. Preemptive screening for IHD may be warranted in this subgroup. <h3>References</h3> Uyar B, Solak A, Genç B, et al. Evaluation of Arterial Stiffness in Patients with Behçet9s Disease by Using Noninvasive Radiological Methods such as Intima-Media Thickness of the Carotid, Ankle-Brachial Pressure Index, Coronary Artery Calcium Scoring, and Their Relation to Serum Fetuin-A Levels: A Case-Control Study. Ann Dermatol. 2015;27:702. Springer J, Villa-Forte A. Thrombosis in vasculitis: Curr Opin Rheumatol. 2013;25:19–25. Misra DP, Shenoy SN. Cardiac involvement in primary systemic vasculitis and potential drug therapies to reduce cardiovascular risk. Rheumatol Int. 2016;37.1:151–167. Pandey A, Garg J, Krishnamoorthy P, et al. Predictors of Coronary Artery Disease in Patients with Behcet9s Disease. Cardiology. 2014;129:203–206. Seyahi E, Memisoglu E, Hamuryudan V, et al. Coronary atherosclerosis in Behçet9s syndrome: a pilot study using electron-beam computed tomography. Rheumatology. 2004;43:1448–50. <h3>Disclosure of Interest</h3> None declared
THU0602 Worker productivity loss remains a major issue for patients with inflammatory arthritis and osteoarthritis: results from the international eular-pro worker productivity study
Authors: S Leggett, A Bosworth, C Hoffstetter, A Boonen, D Lacaille, C Mihai, C Talli, S Hagel, G Crepaldi, S Ramiro, S Dadoun, S Verstappen
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Rheumatic and Musculoskeletal Diseases such as Inflammatory arthritis (IA) and osteoarthritis (OA) are one of the biggest causes of disability and worker productivity loss which has recently been recognized by European policy makers and the World Health Organization (WHO). However, limited information is available about job characteristics and the level of both presenteeism and absenteeism in employed persons with IA or OA across countries. <h3>Objectives</h3> To describe job characteristics and worker productivity loss in patients with IA and OA in Europe and Canada. <h3>Methods</h3> Patients with IA or OA in paid employment from seven countries within Europe and from Canada were recruited to the EULAR-PRO Worker productivity study. Patients completed a questionnaire including questions about their job, job characteristics and the Work Productivity and Activity Impairment Questionnaire (WPAI) measuring percent hours absent and the percentage their disease affected productivity while working (0–100%=disease completely prevented work). Patients also completed several health-related patient reported outcome measures, including: the Health Assessment Questionnaire (HAQ), Visual Analogue Scale (VAS) general well-being, and EuroQol-5D (EQ-5D). <h3>Results</h3> 503 patients were included in this large international study. Mean (SD) age was 47 (10) years, median [IQR] disease duration 12 [5, 21] years and 94% had IA. 42% had a predominately mentally demanding job, 10% physically demanding job, and 48% a combination; with overall 34% reporting their job being very demanding (see table for country specific results). Respectively 12% and 5% of patients were able to often or always postpone work tasks if need be, whilst, respectively 19% and 51% never or sometimes received help from colleagues which may depend on job/employment type and company size. Twenty-one% of patients reported that they missed time off work due to ill-health in the past week (median [IQR] % time missed due to ill-health 20% [9–50]). Interestingly, a total of 11% were unsatisfied with their current job; and 23% of patients did not disclose their disease to their employer. <h3>Conclusions</h3> This is one of the largest international studies investigating worker productivity loss in patients with IA and OA. It highlights the burden of the disease across countries and the importance of increasing awareness of rheumatological conditions in order to prevent presenteeism and long-term sick leave by providing the best available intervention to the individual patient in paid employment. <h3>Disclosure of Interest</h3> None declared
Endoscopic submucosal dissection for a heterotopic gland in the transverse colon
Authors: Sayo Ito, Kinichi Hotta, Kenichiro Imai, Tadakazu Shimoda, Hiroyuki Ono
Journal: Endoscopy (2017)

It is rare for ectopic gastric mucosa to develop in the colorectum, and there are few reported cases [1] [2] [3]. To the best of our knowledge, there are no case reports of a heterotopic gland in the colon.
THU0389 Is there any role of immunogenicity on the response to the anti-tumor necrosis factor alpha therapy in patients with ankylosing spondylitis: the first results of a prospective cohort study
Authors: S Akar, M Cinar, G Sargin, O Karadag, G Kinikli, M Ozmen, O Gercik, U Kalyoncu, S Yilmaz, T Senturk, G Keser, G Hatemi, F Yargucu, Y Ozguler, A Cefle, D Kozaci, D Solmaz, B Kisacik
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Although anti-tumour necrosis factor agents (anti-TNFs) are very effective in most patients with ankylosing spondylitis (AS) significant proportion of patients quit the treatment due to non-response or adverse events. The development of anti-drug antibodies (ADAs) and low serum drug levels might have a mechanistic role in loss of efficacy of or the development of adverse events in patients treated with anti-TNFs. There is limited data regarding the immunogenicity of anti-TNFs in patients with AS. <h3>Objectives</h3> Therefore the aim of this study was to evaluatethe relationship between the formation of ADAs, serum through drug levels and clinical response to anti-TNFs in patients with AS. <h3>Methods</h3> In total 350 AS patients with a new anti-TNF agent prescription in the last two weeks period were planned to include this multi-center prospective observational cohort study. Herein we are presenting the data of first 102 patients who had &gt;3months follow-up. Clinical data and serum samples were collected at baseline and at every three months of treatment. Serum drug levels and ADAs were measured by ELISA in one center to avoid inter-assay variability. <h3>Results</h3> 102 biologic naïve AS patients (75 [74%] male, mean (±SD) age; 37.2±10.7 years) who started anti-TNF agents (14 infliximab [13.7%], 27 adalimumab [26.5%], 33 etanercept [32.4%] and 28 golimumab [27.5%]) were included in the present analysis. In comparison to baseline values BASDAI, ASDAS-CRP and CRP values were significantly decreased in third months of follow-up (<i>P</i>&lt;0.001) (table). At 12 weeks of follow-up 9 patients (9%; 2 on infliximab and 7 adalimumab) had ADAs and 20 (20%; 10 on adalimumab, 4 infliximab, 4 golimumab and 2 etanercept) had no detectable drug levels.The presence of ADAs were significantly correlated with serum drug levels (<i>P</i>&lt;0.001). Up to 12 months of follow-up none of patients treated etanercept developed ADAs. Third month BASDAI and ASDAS-CRP values were significantly higher in patients with ADAs (BASDAI values were 5.2±1.4 vs 3.0±1.8; <i>P</i>&lt;0.001 and ASDAS-CRP values were 3.1±1.0 vs 1.9±1.1; <i>P</i>&lt;0.001) (figure) and patients with no detectable drug levels BASDAI values were 4.1±1.8 vs 2.9±1.8; <i>P</i>=0.012 and ASDAS-CRP values were 2.7±1.3 vs 1.9±1.0; <i>P</i>=0.015). <h3>Conclusions</h3> ADAs against anti-TNF agents might develop as early as 12 weeks of treatment. Our results confirm that ADA development may hinder the anticipated response to anti-TNF agents in patients with AS. <h3>Disclosure of Interest</h3> None declared