tbuckley/cabot-search huggingface dataset:
TRIBE-2 by GONO group: A phase III strategy study in the first- and second-line treatment of unresectable metastatic colorectal cancer (mCRC) patients.
Authors: Chiara Cremolini, Fotios Loupakis, Luca Boni, Sara Lonardi, Vittorina Zagonel, Elena Ongaro, Gianluca Masi, Emiliano Tamburini, Cristina Granetto, Monica Ronzoni, Lisa Salvatore, Filippo Pietrantonio, Giacomo Allegrini, Samantha Di Donato, Gianluca Tomasello, Daniele Santini, Stefano Sergio Cordio, Domenico C. Corsi, Giuseppe Fornarini, Alfredo Falcone
Journal: Journal of Clinical Oncology (2016)

TPS3629 Background: Chemotherapy plus bevacizumab (bev) is a standard first-line treatment for unresectable mCRC patients. The intensity of the chemotherapy backbone may be modulated from one to three drugs regimens according to patients’ general conditions and comorbidities, treatments’ objectives, and disease characteristics. TRIBE study demonstrated a significant advantage in progression-free (PFS) and overall survival (OS) for FOLFOXIRI plus bev as compared with FOLFIRI plus bev. Based on recent evidences supporting the de-intensification of the upfront regimen after 4-6 months, alternating induction and maintenance phases is a valuable option. Moreover, the prolonged inhibition of angiogenesis, and in particular the continuation of bev beyond disease progression, is an efficacious strategy in the treatment of mCRC patients. Based on these considerations, we designed the present phase III study aiming at comparing two different strategies in the first- and second-line treatment of mCRC. Methods: TRIBE-2 is a prospective, open-label, multicentric phase III randomized trial in which unresectable mCRC patients, previously untreated for the metastatic disease, are randomized to receive first-line mFOLFOX-6 plus bevacizumab followed by FOLFIRI plus bevacizumab after progression (arm A) or FOLFOXIRI plus bevacizumab followed by re-introduction of the same regimen after progression (arm B). All combination treatments are repeated up to 8 cycles and followed by maintenance with a fluoropyrimidine plus bev, in order to shorten the duration of more intensive treatments while prolonging as more as possible oxaliplatin- and irinotecan-free intervals. The primary endpoint is Progression Free Survival 2 (PFS2), defined as the time from randomization to disease progression on any treatment given after 1st progression or death. Assuming a median PFS2 of 15 months in arm A, 654 subjects will be needed to detect a HR for PFS2 of 0.77 in favour of arm B with two-sided alpha and beta errors of 0.05 and 0.20, respectively. The trial is now ongoing at 58 Italian centers and from Feb 2015 to Jan 2016 212 patients have been randomized. Clinical trial information: NCT02339116.
THU0695 The RA FLARE questionnaire (RA-FQ) is responsive to change in ra symptoms and impacts in clinical and observational trials
Authors: SJ Bartlett, VP Bykerk, B Fautrel, F Guillemin, A den Broeder, R Alten, R Christensen, E Choy, D Furst, S Hewlett, A Leong, L March, T Woodworth, BIO Clifton
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The RA-FQ is a new tool to measure RA flares. We have previously provided evidence of construct validity and reliability.1 <h3>Objectives</h3> We evaluated sensitivity to change of the RA-FQ in clinical trials and observational studies of RA patients with low disease activity. <h3>Methods</h3> RA patients in observational studies [CATCH-Canada (n=896) and STPR-France (n=138)], and an RCT (DRESS-Netherlands; n=178) completed 5 items asking whether they were in flare (yes/no), and if so, the severity and duration. We selected patients who said they were not in flare and had a DAS28 &lt;3.2 at thefirst visit (V1). Flare at the next study visit (V2) was defined three ways: 1) patient report (yes/no); 2) patient report-stringent (Boolean: patient report yes AND severity ≥4/10 AND duration &gt;7 days [to increase this reflected increased inflammatory disease activity]; and c) DAS definition often used in studies (DAS28&lt;3.2 at V2 required increase of 1.2; DAS≥3.2 at V2 required increase of 0.6). We compared RA-FQ scores with other PROs and disease activity indicators between flaring and non-flaring patients at V2. Effect size was estimatedusing Cohen9s SMD. We hypothesized that at V2, RA-FQ scores would be similar in patients not flaring at both visits, and would be significantly higher in those flaring at V2. <h3>Results</h3> The mean difference in RA-FQ scores at V2 ranged from 7.3 (95% CI 1.4, 13.2) in STPR (DAS def) to 19.6 (95% CI 16.7, 22.6) in CATCH (patient report-stringent). The standardized mean difference effect sizes (SMDES) ranged from 0.82–1.95, and were largest for patient report-stringent in 2 studies. SMDE were strong (range 0.84–2.42) for patient global, MD global, HAQ, DAS28, and other clinical indicators except ESR. The mean difference in RA-FQ scores at V2 ranged from 7.3 (95% CI 1.4, 13.2) in STPR (DAS def) to19.6 (95% CI 16.7, 22.6) in CATCH (patient report-stringent). The standardized mean difference effect sizes (SMDES) ranged from 0.82–1.95, and were largest for patient report-stringent in 2 studies. SMDE were strong (range 0.84–2.42) for patient global, MD global, HAQ, DAS28, and other clinical indicators except ESR. <h3>Conclusions</h3> Data from clinical and observational studies support the responsiveness of the RA-FQ in detecting change over time. The robust psychometric properties of the RA-FQ suggest it reliably detects clinically relevant worsening of RA symptoms consistent with increased disease activity and support its use in research and clinical care. <h3>References</h3> Bykerk V et al. RMD Open 2016;2(1):e000225. <h3>Disclosure of Interest</h3> None declared
OP0340 Weight loss for overweight and obese individuals with gout: a systematic review of longitudinal observational studies
Authors: SM Nielsen, EM Bartels, M Henriksen, H Gudbergsen, H Bliddal, A Astrup, FK Knop, L Carmona, W Taylor, JA Singh, F Perez-Ruiz, LE Kristensen, R Christensen
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Weight loss is a commonly recommended treatment for gout, but the magnitude of effect to expect has to our knowledge not previously been evaluated in a systematic review. <h3>Objectives</h3> The aim of this systematic review was to determine the benefits and harms associated with weight loss in overweight patients with gout. <h3>Methods</h3> Based on a pre-defined protocol (CRD42016037937), we searched six databases for longitudinal studies, quantitatively reporting the effect of weight loss in overweight gout patients. Risk of bias was assessed using the ROBINS-I tool. The quality of the evidence was assessed using GRADE. <h3>Results</h3> From 3,991 potentially eligible studies, 10 were included (incl. one RCT). Interventions included diet with/without physical activity, bariatric surgery, diuretics, metformin, or no intervention. Due to clinical heterogeneity of the included studies, data are presented for each study and synthesised separately. The effect on serum uric acid (sUA) ranged from -168 to 30 μmol/L, and 0% to 60% patients achieved sUA normalisation (i.e. sUA &lt;360 μmol/L). Six out of eight studies (75%) showed beneficial effects on gout attacks. A dose-response relationship was indicated in two studies for sUA, sUA normalisation and gout attacks. At short term (&lt;3 months) after bariatric surgery, one study showed temporary increase in sUA, and another showed temporary increased number of gout attacks. Other possible harmful effects, measured by proxies such as withdrawals due to adverse events and serious adverse events, were poorly reported. <h3>Conclusions</h3> The available evidence is in favour of weight loss for overweight gout patients, with low, moderate and low quality of evidence for an effect on sUA, sUA normalisation, and gout attacks, respectively. At short term, temporary increased sUA and gout attacks may occur after bariatric surgery. There is an urgent need to initiate rigorous prospective studies (preferably RCTs) to provide more trustworthy estimates of benefits and harms of weight loss in overweight gout patients. <h3>References</h3> Richette P, Doherty M, Pascual E, et al. 2016 updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis 2016:1–14, doi: 10.1136/annrheumdis-2016-209707. <h3>Disclosure of Interest</h3> None declared
FRI0140 Comorbidity and surgery history of rheumatoid arthritis patients who are receiving biological agent
Authors: B Armagan, A Sari, A Erden, L Kilic, EC Erdat, O Karadag, A Akdogan, S Apras Bilgen, U Kalyoncu, I Ertenli, S Kiraz
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Rheumatoid artritis (RA) is a chronic and autoimmune disorder that primarily affects middle and older ages. Comorbidities are important during RA treatment. <h3>Objectives</h3> We aim to determine the frequency of comorbidites and surgical history in the RA patients who receive biological agents. <h3>Methods</h3> Hacettepe University Biologic Registry (HUR-BIO) includes demographic and clinical data of patients treated with biological agent since 2005. By August 2016, 1235 RA patients were recorded in the database. Age, gender, smoking habits, disease duration, rheumatoid factor, anti citrullinated peptide (CCP), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), current and previous treatments, comorbidites and surgical history of patients were analyzed. Comorbidites and surgery history were determined by patients medical records. Disease activity was estimated by the 28-joint activity calculator- C reactive protein (DAS28-CRP). Functional assessment was evaluated by the Health Assessment Questionnaire (HAQ). <h3>Results</h3> Mean age (SD) of the patients (79,8% women) was 53,1 (12,6) and the mean disease duration was 11,0 (7,7) years. Of patients, 166 (16,6%) were older than 65 years. A total of 630 (63%) patients education level were less than high school, 197 (19,7%) of the patients were graduated from university. Smoking habitus of patients was as follows, 599 (59,9%) never smoked, 189 (18,9%) current smoker and 212 (21,2%) ex-smoker. At least one cardiovascular risk factor was detected in 699 (69,9%) patients. Comorbidities and surgical history of patients were shown in the table below. Patients with at least one comorbidity had less frequently female (77.3% vs 84.5%, p=0.007), high seropositivitly of RF (66% vs 57.1%, p=0.004), high patient global assessment (4.4±2.5 vs 3.9±3.9, p=0.007), high fatique score (4.6±3 vs 3.9±3.1, p=0.001), high pain score (4.8±2.5 vs 4.0±2.8, p=0.009), DAS-28 (3.43±1.39 vs 3.17±1.48, p=0,009) and high HAQ score (0.72±0.59 vs 0.58±0.54, p=0.001) than patients without comorbidities. <h3>Conclusions</h3> Comorbidities and past surgical history should be considered in RA patients when biological therapy is indicated. Comorbidities is one of the important conditions for physicians to manage patients. Cardiovascular, chronic viral infection such as hepatitis B and C, tuberculosis and cancer have to be investigated to start biological treatments. Surgical history such as cataracts, ortopedic surgery were also important for clinicians. HURBIO data demonstrated that patients with at least one comorbidities reflects more negative patient outcome measures. <h3>Disclosure of Interest</h3> None declared
THU0633 Temperature sensitivity in patients with rheumatoid arthritis
Authors: P Mandl, F Alasti, A Kerschbaumer, R Kaltenberger, T Krennert, GM Supp, U Landesmann, JS Smolen, D Aletaha
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Studies evaluating weather sensitivity among patients with rheumatoid arthritis (RA) have yielded conflicting results. <h3>Objectives</h3> To evaluate whether patients with RA exhibit sensitivity to outside temperature. <h3>Methods</h3> We assessed correlation between mean daily temperature and self-reported pain (by visual analogue scale), and patient9s global assessment of disease activity (PGA). Assessments documented in the RA database of our department as well as the average temperature obtained from the Central Institute for Meteorology and Geodynamics, were matched on a daily basis for a period of 10 years between 2005 and 2015 and analyzed using generalized estimating equation (GEE) and a mixed model analysis (MM). Patients with &lt;5 visits in the study period, or with &lt;1 visit/quarter or with pain=0 in ≥3 consecutive visits and those living outside of the catchment area were excluded. Overlap between responsiveness of pain or PGA to temperature was calculated by Cohen9s kappa. <h3>Results</h3> A total of 399 patients with RA (average disease duration at first visit: 6.0±7.6 years, average age: 57.7±13.9 years, 82% female, mean CDAI 19.7±11.5, 59.9% rheumatoid factor positive) were analyzed. Lower temperatures correlated significantly with higher pain levels (estimate: -0.07, p=0.021) in GEE, however the effect size was very small. When we performed MM with temperature as independent variable and VAS pain or PGA as dependent variable, the majority of patients showed no sensitivity to temperature, however 22% of patients were significantly sensitive to cold temperature with an estimate of -0.29 (p&lt;0.0001) for pain and -0.21 (p=0.0005) for PGA (Figure 1). When we evaluated whether patients who demonstrate temperature-sensitivity to pain also exhibit temperature-sensitivity to PGA, we found an excellent overlap between the two patient groups (kappa: 0.81). <h3>Conclusions</h3> Our results indicate that a subgroup of patients with RA show significant sensitivity to cold temperature, and that these patients are characterized by higher pain and PGA levels at lower daily temperatures. These aspects may have to be taken into account in longitudinal analyses of disease activity of RA. <h3>Disclosure of Interest</h3> None declared
SAT0317 Type vi collagen formation: a new objective blood-based marker reflecting fibrosis of the skin in systemic sclerosis
Authors: P Juhl, L Iversen, T Karlsmark, M Karsdal, A-C Bay-Jensen, M Mogensen, AS Siebuhr
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Systemic sclerosis (SSc) is characterized by fibrosis of the skin. The dermis of the skin is rich in type I and III collagen, but other collagens as type VI collagen are present in the skin and play a key role in the organization of type I and III collagen. There is a lack of objective disease activity markers in SSc for frequent assessment of patients. The only measurement of disease activity currently is the subjective modified Rodnan skin score (mRSS). <h3>Objectives</h3> The objective is to examine blood-based markers of type I, III, and VI collagen formation as surrogates of disease activity and fibrosis in SSc. <h3>Methods</h3> SSc patients fulfilling the ACR criteria (n=121) were included. The study included both limited SSc (lSSc, n=79) and diffuse SSc (dSSc, n=42) (approval number H-B-2008–131). Markers of type I, III and VI collagen formation (P1NP, PRO-C3 and PRO-C6, respectively) were measured in serum by ELISA. Difference in the markers between groups were tested by Mann-Whitney T test and correlations were assessed by multiple linear regression adjusting for age, gender and BMI. Discriminative power of the markers was analyzed by ROC AUC on tertiles of mRSS. <h3>Results</h3> There were no significant difference in gender, BMI or disease duration between lSSc and dSSc. The mean age of the population was 57.4 (SD 11.6) years, 84% were female, mean disease duration was 11.7 (SD 8.9) years and mean mRSS was 11.2 (SD 8.6). PRO-C3 and PRO-C6 were significantly higher early (&lt;4 years) dSSc compared to early lSSc patients (both p=0.006). PRO-C6 was significantly elevated in early dSSc compared to late dSSc (p=0.04) and increased in late dSSc compared to late lSSc (p=0.02; Figure). Both PRO-C3 and PRO-C6 correlated with mRSS when adjusted for age, gender, and BMI with R-partial of 0.36 (p=0.0001) and 0.29 (p=0.002), respectively. Both PRO-C3, and PRO-C6 could separate the patient group having the highest tertile of mRSS from the rest with an AUC (95% CI) of 0.73 (0.62–0.82), and 0.74 (0.63–0.83), respectively. Together, PRO-C3 and PRO-C6 could separate the groups with an AUC (95% CI) of 0.77 (0.67–0.86) (Table 1). PRO-C3 and PRO-C6 performed equally well for identification of patients with the highest skin score (highest tertile vs. the middle and lower tertile) with a relative risk of 2.3 (1.4–3.8) (Table 2). The risk of being in the highest tertile of mRSS compared to the lowest were significantly higher with a high PRO-C6 (relative risk 2.6, 95% CI: 1.3–5.2) compared to PRO-C3 (relative risk: 2.2, 95% CI: 1.2–3.8) (Table 2). <h3>Conclusions</h3> Markers reflecting fibrosis (measures of type III and VI collagen formation) could be novel objective, and potentially predictive, biomarkers of disease activity and severity. <h3>Disclosure of Interest</h3> None declared
SP0148 Pathophysiology of established ra synovitis
Authors: B Lauwerys
Journal: Annals of the Rheumatic Diseases (2017)

Access to synovial tissue through - minimally invasive - synovial biopsy procedures led to the implementation of new translational approaches to our understanding of established RA. In this lecture, we will illustrate how the identification of different synovial pathotypes and related molecular pathways translated into clinically relevant phenotypes, such as disease severity or response to therapy. Validation of these concepts in ongoing large-scale multi-centric trials will be key to the integration of synovial assessment tools in clinical practice. <h3>Disclosure of Interest</h3> B. Lauwerys Shareholder of: DNALytics
SAT0434 Network meta-analysis on the efficacy of novel therapeutic agents in patients with psoriatic arthritis
Authors: TT Cheung, MF Tsoi, Y Fei, CS Lau, BMY Cheung
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Novel therapeutic agents are more effective than DMARDs in the management of psoriatic arthritis. However, direct comparisons of efficacy between these novel therapeutic agents are lacking. <h3>Objectives</h3> This network meta-analysis aims to compare the relative efficacies between different novel therapeutic agents. <h3>Methods</h3> Literature searching was conducted in MEDLINE, EMBASE, Scopus, ISI Web of Science, Cochrane Library, Clinicaltrials.gov and recent rheumatology conference abstracts up to Nov 2016. 2 independent researchers analysed the articles. For inclusion, randomised, placebo-controlled trials must report the proportion of patients achieving ACR20, ACR50, ACR70 and PASI75 responses. The outcomes of this network meta-analysis were the proportion of patients achieving ACR20, ACR50, ACR70 and PASI75 responses with reference to placebo and etanercept. Results were analysed using random effect model by R statistics (version 3.3.1) with statistical package netmeta (version 0.9–2). The heterogeneity of the study results was determined by the I<sup>2</sup> statistics. <h3>Results</h3> 18 trials were included into this study. In general, all novel therapeutic agents demonstrated superior efficacies than placebo. With reference to etanercept, apremilast and ustekinumab were associated with less proportions of patients achieving ACR20 response (odds ratio [95% confidence interval]: 20mg apremilast: 0.18 [0.07–0.48]; 30mg apremilast: 0.24 [0.09–0.62]; 45mg ustekinumab: 0.26 [0.09–0.73]; 90mg ustekinumab: 0.32 [0.11–0.90]). Etanercept was not different from apremilast, ustekinumab, golimumab, adalimumab, ixekizumab, certolizumab, ixekizumab and secukinumab in terms of ACR20 and ACR50 responses. Golimumab and infliximab were associated with greater proportions of patients achieving PASI75 response, though the difference did not reach statistical significance. (odds ratio [95% confidence interval]: golimumab: 3.51 [0.44–28.2]; infliximab: 5.97 [0.89–40.2]). <h3>Conclusions</h3> Apremilast and ustekinumab were less efficacious than etanercept in terms of ACR20 response. All the novel therapeutic agents demonstrated comparable efficacies in terms of ACR50, ACR70 and PASI75 responses. <h3>Disclosure of Interest</h3> None declared
FRI0268 Ultrasound vs. magnetic resonance imaging in diagnosis of primary sjÖgren's syndrome
Authors: A Haidmayer, M Magyar, MH Stradner, T De Zordo, A Lutfi, B Unger, WB Graninger, J Hermann, C Dejaco
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Salivary gland (SG) biopsy is the gold standard for the diagnosis of primary Sjögren9s syndrome (pSS). Ultrasound (US) and magnetic resonance imaging (MRI) of the SG are emerging techniques. The comparison of both imaging methods for diagnosis and assessment of functional limitation is yet not well investigated. <h3>Objectives</h3> To assess the accuracy of US and MRI and to define possible cutoff values for the diagnosis of pSS. <h3>Methods</h3> Twenty-three patients with pSS according to AECG criteria and typical histology of the SG biopsy and 12 patients with sicca-syndrome and normal SG histology were included in the study. Two experienced ultrasound experts (C.D. 6y, T.D.Z. 5y) did ultrasound of the SG using a B-mode score (0–48 points [1]) and real-time sonoelastography (RTS; 0–16 pts [2]). Morphology of the parotid glands was also assessed by MRI (0–12 pts). We obtained clinical data (C-reactive protein (CRP), antinucleary-antibodies (ANA), Ro-/La-antibodies, Gamma globulins, patient questionaires ESSDAI and SSDI). The statistically analysis was carried out using Kolmogorov-Smirnov-test, student9s t-test, or Man-Whitney-U-test. Correlations were performed using Spearman-rang-correlations. <h3>Results</h3> Patients with pSS had significantly higher B-mode- (average =25 [2–44] vs. 9 [1–20], p&lt;0.001) and RTS-scores (6.5 [2–13] vs. 4 [1–9], p&lt;0.001) than sicca-patients. The same was also found for MRI-assessment (6,96 vs. 2,33, p=0.001). In a Spearman rank correlation, clinical parameters were linked to the imaging techniques The B-mode showed significant inverse correlations with the Saxon-test (r=-0.505, p=0.002) and a positive correlation with MRI (r=0.792, p&lt;0.0001). No correlation was found for the activity scores ESSDAI (p=0.221) or SSDI (p=0.219). The MRI score had an inverse correlation with the Saxon-test (r=-0.523, p=0.001). Both imaging techniques showed no relationship with ESR or CRP. We also generated ROC curves of both imaging methods to define possible cutoff values for the diagnosis. For B-Mode we would recommend a value of 12 points (sensitivity 82,6% and specificity 91,7%) and for MRI 3.5 points (78,3% and 91,7%). <h3>Conclusions</h3> Sonography and MRI detected typical morphological changes in the SG of pSS with high sensitivity and specificity. Both methods could become valuable tools for the diagnosis of pSS. <h3>References</h3> Hocevar, Ambrozic A, Rozman B, Kveder T, Tomsic M. Ultrasonographic changes of major salivary glands in primary Sjogren9s syndrome. Diagnostic value of a novel scoring system. Rheumatology (Oxford). 2005;44(6):768–72. Rubaltelli, Corradin S, Dorigo A, Stabilito M, Tregnaghi A, Borsato S, Stramare R. Differential diagnosis of benign and malignant thyroid nodules at elastosonography. Ultraschall Med. 2009;30(2):175–9. <h3>Disclosure of Interest</h3> None declared
SP0101 Diagnostic and therapeutic ultrasound-guided procedures
Authors: P Mandl
Journal: Annals of the Rheumatic Diseases (2017)

The lecture will provide an overview of sonography-guided musculoskeletal interventions which can be grouped broadly as diagnostic and therapeutic procedures. Primarily diagnostic procedures include arthrocentesis, biopsy from various musculoskeletal tissues (synovial, bone, muscle etc.), aspiration of fluid from cystic lesions, tendon sheaths and bursae. The therapeutic group features joint and soft tissue injections, needling of periarticular calcification, including barbotage. Both indirect and direct-guidance techniques will be detailed and published literature on accuracy, outcome and safety of sonographic-guided interventions will be reviewed. <h3>Disclosure of Interest</h3> None declared