tbuckley/cabot-search huggingface dataset:
AB0937 Efficacy of new treatments on dactylitis of psoriatic arthritis: update of systematic literature review
Authors: M. Sondag, F. Verhoeven, X. Guillot, C. Prati, D. Wendling
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Dactylitis is a frequent disabling feature of psoriatic arthritis (PsA). Therapeutic strategy on dactylitis is not really codified. <h3>Objectives</h3> The objective of the study was to evaluate efficacy on dactylitis of differents treatments actually available in PsA. <h3>Methods</h3> We performed a literature review from June 2014 to October 2017 based on Pubmed, using the search terms "psoriatic arthritis" and "treatment" with only clinical trials. 89 articles were identified (English-language reports only). Thus, we selected only randomised, double-blind placebo-controlled trials in which analysis of dactylitis was exposed: 11 articles were selected for full review. <h3>Results</h3> Significant improvement of dactylitis (p&lt;0.05) compared to placebo was observed with the use of golimumab in GO-VIBRANT, ustekinumab in PSUMMIT-1/PSUMMIT-2 trial, with apremilast 30 mg only in PALACE 3, with ixekizumab and adalimumab in SPIRIT-P1 (post hoc analysis). For secukinumab, results are different: McInnes <i>et al.</i> (FUTURE 2) found no significant efficacy with 47% of dactylitis resolution at 24 weeks for secukinumab vs 11% for placebo (p=0.9195). At the opposite, Kavanaugh <i>et al.</i> (FUTURE 2) demonstrated secukinumab efficacy on anti-TNF-naïve (300 mg and 150 mg dosages) and anti-TNF-exposed patients (only 300 mg). For Mc Innes <i>et al.</i>, clazakizumab permitted great decreases in the mean number of dactylitis from baseline to weeks 16 and 24 but no statistical data are available in the report. Similarly, in a recent publication, promising results were found for tofacitinib and abatacept, but no statistical data are available. At the opposite, no significant efficacy was demonstrated in a randomised controlled trial with brodalumab. Calculating of effect size was possible and available only in one study: secukinumab's effect size was 4.35 in McInnes study (FUTURE 2). Calculation of Odds Ratio (with of residual dactylitis between treatment and placebo groups was possible on part of studies with significant results for clazakizumab (200 mg dosing) and secukinumab in patients TNF exposed (figure 1). <h3>Conclusions</h3> Dactylitis was always used as secondary outcome criteria with heterogeneous results. So conclusions need to be cautious. This invalidating clinical manifestation need to be evaluated as a primary outcome in the future. <h3>Disclosure of Interest</h3> None declared
A Phase <scp>II</scp> Trial of Lutikizumab, an Anti–Interleukin‐1α/β Dual Variable Domain Immunoglobulin, in Knee Osteoarthritis Patients With Synovitis
Authors: Roy M. Fleischmann, Henning Bliddal, Francisco J. Blanco, Thomas J. Schnitzer, Charles Peterfy, Su Chen, Li Wang, Sheng Feng, Philip G. Conaghan, Francis Berenbaum, Jean‐Pierre Pelletier, Johanne Martel‐Pelletier, Ole Vaeterlein, Gurjit S. Kaeley, Wei Liu, Matthew P. Kosloski, Gwen Levy, Lanju Zhang, Jeroen K. Medema, Marc C. Levesque
Journal: Arthritis & Rheumatology (2019)

Objective To assess the efficacy and safety of the anti–interleukin‐1α/β (anti– IL ‐1α/β) dual variable domain immunoglobulin lutikizumab ( ABT ‐981) in patients with knee osteoarthritis ( OA ) and evidence of synovitis. Methods Patients (n = 350; 347 analyzed) with Kellgren/Lawrence grade 2–3 knee OA and synovitis (determined by magnetic resonance imaging [ MRI ] or ultrasound) were randomized to receive placebo or lutikizumab 25, 100, or 200 mg subcutaneously every 2 weeks for 50 weeks. The coprimary end points were change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) pain score at week 16 and change from baseline in MRI ‐assessed synovitis at week 26. Results The WOMAC pain score at week 16 had improved significantly versus placebo with lutikizumab 100 mg ( P = 0.050) but not with the 25 mg or 200 mg doses. Beyond week 16, the WOMAC pain score was reduced in all groups but was not significantly different between lutikizumab‐treated and placebo‐treated patients. Changes from baseline in MRI ‐assessed synovitis at week 26 and other key symptom‐ and most structure‐related end points at weeks 26 and 52 were not significantly different between the lutikizumab and placebo groups. Injection site reactions, neutropenia, and discontinuations due to neutropenia were more frequent with lutikizumab versus placebo. Reductions in neutrophil and high‐sensitivity C‐reactive protein levels plateaued with lutikizumab 100 mg, with further reductions not observed with the 200 mg dose. Immunogenic response to lutikizumab did not meaningfully affect systemic lutikizumab concentrations. Conclusion The limited improvement in the WOMAC pain score and the lack of synovitis improvement with lutikizumab, together with published results from trials of other IL ‐1 inhibitors, suggest that IL ‐1 inhibition is not an effective analgesic/antiinflammatory therapy in most patients with knee OA and associated synovitis.
THU0318 Treating psoriatic arthritis to target: comorbidities, non-adherence and factors related to the health system prevent escalation of therapy in real life
Authors: M. Ferreira, R. Xavier, E. Abbeg, O. Martins, F. Menegat, C. Kohem, A. Gasparin, N. Andrade, V. Hax, D. Viecceli, C. Brenol, J.C. Brenol, P. Palominos
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Although the treat-to-target (T2T) strategy in psoriatic arthritis (PsA) clinical trials resulted in better outcomes in domains such as joints, skin, function and quality of life compared to standard care, in real life several factors affect such a strategy <sup>1</sup>. <h3>Objectives</h3> To determine the prevalence of patients achieving minimal disease activity (MDA) in our PsA clinic and the reasons why therapy in patients not achieving MDA was not optimised. <h3>Methods</h3> An observational, retrospective cross-sectional study nested in a cohort study was conducted; medical records of patients attending PsA clinic in a public university hospital were reviewed. Demographic data, current treatment and components of the MDA score were collected. When patients were not in MDA but the treatment was not optimised, the reasons for the non-escalation of therapy were recorded. <h3>Results</h3> MDA score was available in 113 visits, corresponding to 69 patients. Mean age of patients was 57.4±10.6, 53.6% (n=37) were females and 40.6% (n=28) were treated with biological drugs. MDA was reached in 31.0% (n=35) of visits; 36.2% (n=25) of the patients achieved MDA in at least one visit during the 8 months follow-up. There was no statistical difference in the proportion of patients achieving MDA according to treatment prescribed (biological DMARDs versus synthetic conventional DMARDs) (p=0.979). Although MDA was not achieved in 69.0% (n=78) of visits, optimisation of therapy was done in only 42.3% (n=33) of those visits. The main reasons which prevented treatment escalation were: physician impression of clinical remission and MDA overestimated by comorbidities and chronic deformities (57.7%, n=26), non-adherence to previous prescription (17.8%, n=8), delay to receive drugs from health insurance (17.8%, n=8), adverse events (11.1%, n=5), patient low cognitive level (6.7%, n=3) and patient refusal to escalate therapy (4.4%, n=2). In visits with impression of remission by rheumatologist, the skin and the swollen joint components of the MDA score were achieved in more than 80% of this visits (80.8%, n=21). <h3>Conclusions</h3> Rheumatologists are reluctant to escalate therapy in PsA even if patients are not in MDA if "objective" components of the MDA score such as skin and swollen joint counts are reached. Comorbid conditions, patients non-adherence to therapy and factors related to the health system influence a tight control strategy in the real life clinical practice. <h3>Reference</h3> [1] Coates LC, et al. Effect of tight control of inflammation in early psoriatic arthritis (TICOPA): a UK multicenter, open-label, randomized controlled trial. Lancet2015;386:2489–98. <h3>Disclosure of Interest</h3> None declared
Probing the Meaning of Persistent Propeptide Release in Type 1 Diabetes
Authors: Steven E. Kahn, Andrew T. Templin, Rebecca L. Hull, C. Bruce Verchere
Journal: Diabetes Care (2019)

Type 1 diabetes is well recognized to be immune mediated, resulting in destruction of β-cells. That this eradication is not always complete was evident in an early report from the Diabetes Control and Complications Trial (DCCT) showing that 11% of adult participants with type 1 diabetes for more than 5 years had measurable C-peptide in the fasting state and following mixed-meal stimulation, while no adolescents had evidence of such (1). Further, in participants with measurable C-peptide responses, C-peptide declined in all after a year of randomized therapy, with this decline being less in those who received intensive insulin therapy. Subsequently, it was shown in adolescents that 2 weeks of intensive insulin therapy, compared with conventional therapy, resulted in improved β-cell function a year later along with superior glucose control (2). In addition to C-peptide, proinsulin has also been shown to be circulating in individuals with type 1 diabetes at the time of diagnosis and to be still measurable 30 months later (3,4). Thus, there is long-standing evidence that at the time of diagnosis and subsequently, individuals with type 1 diabetes have β-cells still capable of synthesizing proinsulin, and many can process it to C-peptide and insulin.

In the current issue of Diabetes Care , Sims et al. (5) report longitudinal findings on proinsulin secretion in type 1 diabetes using a large number of samples from the T1D Exchange. They divided their subjects into three groups based on stimulated C-peptide responses to a mixed meal. We have categorized these groups as having absent, intermediate, and high C-peptide responses, although the latter are a great deal lower than what is observed in healthy people. Individuals in the absent group had C-peptide responses that were below the reliable lower detection limit of the assay, and they were not studied further. These …
FRI0310 Achievement of low disease activity in lupus patients treated with belimumab is independent of serologic status at baseline: a real-life observational study
Authors: A. Fanouriakis, C. Adamichou, S. Koutsoviti, S. Panopoulos, C. Staveri, A. Klagou, C. Tsalapaki, L. Pantazi, S. Konsta, C.P. Mavragani, D. Dimopoulou, S. Ntali, G. Katsikas, K.A. Boki, D. Vassilopoulos, P. Konstantopoulou, S.-N. Liossis, A. Elezoglou, M. Tektonidou, P. Sidiropoulos, A. Erden, P.P. Sfikakis, G. Bertsias, D.T. Boumpas
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Low disease activity is a validated target of systemic lupus erythematosus (SLE) therapy. <h3>Objectives</h3> τo assess the ability of belimumab to induce low disease activity states in real-life setting. <h3>Methods</h3> Multicentre prospective observational study of SLE patients receiving belimumab due to active disease, refractory to at least one conventional immunosuppressant. Disease activity, including attainment of lupus low disease activity state (LLDAS) and remission-on-glucocorticoids (GC) (clinical SLEDAI-2K=0 with prednisone ≤5 mg/day), accrual of organ damage, flares and side effects were documented. <h3>Results</h3> Ninety-one patients were included [94.5% women, mean (SD) age 45.9 (12.5) years]. Most frequent manifestations were arthritis (76.7%), rash (72.5%), serologic activity (low C3/C4 and/or high anti-dsDNA; 54.9%), hair loss (47.2%) and mucosal ulcers (27.5%). Median (range) duration of treatment was 10.5 (3.0–42.1) months. Belimumab decreased average SLEDAI-2K, physician global assessment and daily prednisone dose over time, as early as 3 months after initiation. Complete withdrawal of GC was achieved in 17.8%, 22.5%, 31.7% and 23.3% at 3, 6, 9 and 12 months, respectively. The number of flares and severe flares was reduced by 62% and 50%, respectively, during the first year of treatment. Although reduction in clinical SLEDAI-2K was more pronounced in patients who were serologically active (from 8 to 1.5 at 12 months) compared to serologically inactive (from 6 to 4) at baseline, attainment of low disease activity states (LLDAS or remission) did not differ between groups and was reached by more than 40% of completers after 9–12 months (figure 1). Twenty patients (22.0%) discontinued treatment due to inadequate response and two due to side effects potentially related to the drug. <h3>Conclusions</h3> Belimumab is efficacious in achieving low disease activity in over 40% of active SLE patients, accompanied by complete GC discontinuation in more than 20%. Serologically active and inactive patients respond equally to the drug. <h3>References</h3> [1] Franklyn K, et al. Definition and initial validation of a Lupus Low Disease Activity State (LLDAS). Ann Rheum Dis. 2016;75(9):1615–21. [2] Zen M, et al. Prolonged remission in Caucasian patients with SLE: prevalence and outcomes. Ann Rheum Dis. 2015;74(12):2117–22. <h3>Disclosure of Interest</h3> None declared
SP0125 How big data and machine learning could change the game
Authors: S. Khalid
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> With recent advances in the acquisition and digitisation of medical data, the use of routinely collected health data for research is on the rise. Routinely collected data comes with the promise of the 3 V's of "big data": volume, velocity, and variety. Recent recommendations by the UK National Institute for Health and Care Excellence and the Academy of Medical Sciences have therefore acknowledged the potential for data science methods to play an increasingly important role in healthcare research. Against this backdrop of growing data and increasing computational resources, the use of data science methods including machine learning is becoming popular for analysing large-scale medical datasets. This talk provides a brief overview of machine learning methods for healthcare applications including an introduction to supervised and unsupervised learning, followed by real-world examples of data analysis using machine learning, such as (a) the development of prognostic models for clinical risk assessment, and (b) mining of electronic health records for detecting patterns and phenotypes within a population. <h3>Disclosure of Interest</h3> None declared
Clinical challenges in a patient with two BRAF V600E-mutated diseases
Authors: Ella Willenbacher, Wolfgang Willenbacher, Judith Loeffler-Ragg
Journal: Thorax (2019)

EW: A 51-year-old Caucasian male smoker (>30 pack-year) was referred due to generalised lymphadenopathy and disseminated, apical accentuated pulmonary nodules (up to 12 mm) on CT scans that demonstrated an elevated 18F-FDG uptake. There was a history of childhood pulmonary tuberculosis with ongoing positivity in the interferon-gamma release assay. The patient had night sweats and frequent coughs.

Lymph node and bone marrow biopsies demonstrated infiltration by a small cell lymphocytic lymphoma-Non Hodgkin Lymphoma (SCL-NHL) with chronic lymphocytic leukemia (CLL-like) immunophenotype (Matutes score 4/5) staged as Ann Arbor IV B disease (figure 1A,B).



Figure 1 
Figure demonstrates results of the pathological and molecular analysis of biopsies from a lymph node (LN) affected by a small cell lymphocytic lymphoma and a pulmonary biopsy (PB) of the same patient affected by a PLCH. (A) HE TCT Thymin-Cytosin-Thymin (DNA base codes); PLCH, pulmonary …
The Prognostic Impact of Baseline Positron Emission Tomography (PET) Imaging in Untreated High Risk (HR) Follicular Lymphoma (FL): Analysis from E2408, the Bortezomib Induction or Novel Imid® Continuation (BIONIC) Study
Authors: Lucia Baratto, Opeyemi Jegede, Fangxin Hong, Thomas M. Habermann, Ranjana Advani, Randy D. Gascoyne, Lale Kostakoglu, Thomas E. Witzig, Erik A. Ranheim, Brad S Kahl, Andrew Quon, Andrew M. Evens
Journal: Blood (2018)
FRI0439 The promising role of lung mri in detecting systemic sclerosis (SSC)-related interstitial lung disease (ILD)
Authors: L. Gargani, C. Bruni, D. De Marchi, C. Romei, S. Guiducci, S. Bellando-Randone, G.D. Aquaro, A. Pepe, F. Falaschi, A. Pingitore, M. Matucci-Cerinic
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Interstitial lung disease (ILD) is very frequent and highly disabling in patients with systemic sclerosis (SSc). Magnetic resonance imaging (MRI) is not routinely used for the evaluation of the lung, since MRI generally provides a less detailed view of the pulmonary parenchyma, as well as poorer spatial resolution, compared to the non-invasive gold-standard of high resolution computed tomography (HRCT). Thus, its usefulness in the evaluation of interstitial lung disease (ILD) is limited at present. <h3>Objectives</h3> To evaluate MRI signals in different pathological and non-pathological lung areas, and to establish their clinical and instrumental correlations. <h3>Methods</h3> Thirty-two SSc patients underwent a cardiac MRI with dedicated lung scanning and chest HRCT on the same day. One-hundred-thirty-five regions of interest (ROIs) were identified, and STIR and T1 sequences were acquired[before (T0) and after 5 (T5), 10 (T10) and 15 (T15) minutes from gadolinium injection]. The ROIs were classified according to HRCT as normal, dependent areas (probably related to blood pooling in supine position) and pathological areas(ground glass ±reticulation on HRCT). Mean STIR and T1 times were also calculated for each patients, and correlated with FVC, DLco, B-lines on lung ultrasound and HRCT semi-quantitative scoring (Scleroderma Lung Study score). Patients were followed-up and lung worsening was defined on the basis of clinical judgement and at least &gt;15% DLco decline. <h3>Results</h3> Mean STIR and mean T1 times were significantly different between normal, dependent and pathologic areas (p&lt;0.001 between groups). Patients’ mean STIR showed a significant correlation with DLco (R=−0.56, p&lt;0.01), HRCT Scleroderma Lung Study score (R=0.52, p&lt;0.01) and B-lines on lung ultrasound (R=0.63, p&lt;0.01). The mean STIR of the 10 patients who developed a worsening pulmonary involvement had significantly different MRI signal intensity in comparison to the 25 patients without worsening pulmonary involvement (125±46 vs 66±37 msec, p&lt;0.01). <h3>Conclusions</h3> Our data highlight the usefulness of lung MRI in SSc patients to differentiate normal, dependent and pathologic areas, without need for contrast medium administration, and with good correspondence to other functional and imaging parameters. STIR values may have prognostic implications to predict lung worsening. Lung MRI, although still very preliminary, is a promising imaging tool that in the future may integrate HRCT in SSc-related ILD. <h3>Disclosure of Interest</h3> None declared
Opposing Pathogenesis of Germline SAMD9/SAMD9L Variants in Adult Myelodysplastic Syndrome (MDS)
Authors: Yasunobu Nagata, Satoshi Narumi, Yihong Guan, Bartlomiej P. Przychodzen, Cassandra M. Hirsch, Hideki Makishima, Hirohito Shima, Victor Pastor Loyola, Teodora Kuzmanovic, Tomas Radivoyevitch, Vera Adema, Hassan Awada, Kenichi Yoshida, Francesc Sole, Babal K. Jha, Rabi Hanna, Thomas Laframboise, Seishi Ogawa, Mikkael A. Sekeres, Marcin W. Wlodarski, Jorg Cammenga, Jaroslaw P. Maciejewski
Journal: Blood (2018)
Vitamin D status and bone health: a possible inverse association
Authors: Toshihiro Sugiyama
Journal: BMJ (2019)

Mendelian randomisation analyses of relatively healthy, community dwelling individuals indicate a possible inverse relation between vitamin D status and bone health. Trajanoska and colleagues measured fracture risk (odds ratio per standard deviation decrease 0.84, 95% confidence interval 0.70 to 1.02, P=0.07)1 and Larsson and colleagues …
FRI0187 Lipoprotein (A) and possible related factors in patients with spondyloarthritis. results of the carma study
Authors: C. García-Gómez, M. Martín-Martínez, C. Fernández-Carballido, S. Castañeda, C. González-Juanatey, M. González Fernández, R. Sanmartí, J. García Vadillo, B. Fernández Gutiérrez, M. García Arias, F. Manero, J. Senabre, A. Rueda, S. Ros, J. Pina, A. Erra, I. Möller, J. Llorca, M. González-Gay
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Cardiovascular disease (CVD) is the main cause of mortality and morbidity in patients with spondyloarthritis (SpA), partially explained by traditional CV risk factors (CVRF). Other non-conventional CVRF, probably related to chronic systemic inflammation, may be involved. In this sense, lipoprotein (a) [Lp (a)], an non-conventional risk factor with proatherogenic and thrombogenic properties, could be involved, since it seems to act as an acute-phase reactant, there are few data on this aspect in these patients. <h3>Objectives</h3> To evaluate the prevalence of hyperlipoproteinemia (a) in patients with SpA and analyse the possible related factors. <h3>Methods</h3> Analysis of the baseline visit of patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) of the CARMA project (CARdiovascular in Reumatology), a prospective cohort study of 10 years of follow-up, to evaluate the cardiovascular risk in chronic rheumatic inflammatory diseases, including rheumatoid arthritis, AS and PsA, followed in 67 Spanish rheumatology centres. A multivariate logistic regression model was performed, in which the dependent variable was hyperliproteinemia (a), defined as the plasma concentration of lipoprotein (a) [Lp (a)]≥50 mg/dl. Sociodemographic factors and those related to the disease itself have been included as independent variables. <h3>Results</h3> 1459 patients were analysed, 738 with AS and 721 with PsA. Plasma concentrarions of Lp(a) were available in 57.7% of the patients with AS and in 57.1% of the patients with PsA. A 19.2% (95% CI: 16.80–22.05) of the patients with SpA, 20.7% (95% CI: 16.91–24.82) of AS and 17.7% (95% CI: 14.15–21.75) of PsA, respectively, had hyperlipoproteinemia (a), without statistically significant differences with respect to the control group: 16.7% (95% CI: 13.23–20.86; p=0.326). After adjusted for age and sex, only patients with AS were more likely to have hyperlipoproteinemia (a) than the control grup (OR: 1.806, 95% CI: 1177–2.771, p=0.007). In the model adjusted for possible confounding factors, high values of apolipoprotein B in all patients, non-steroidal anti-inflammatories in AS, and sex (men) and kidney disease as comorbidity in PsA, were associated with a higher probability of presenting hyperlipoproteinemia (a). <h3>Conclusions</h3> Patients with AS have a higher percentage of hyperlipoproteinemia (a) compared to the control group. No specific factors of the disease have been identified that are associated with hyperlipoproteinemia (a) in each of the analysed groups. <h3>Disclosure of Interest</h3> None declared