tbuckley/cabot-search huggingface dataset:
AB0758 Audit on ustekinumab drug survival in a district general hospital versus psummit 1 trial results
Authors: G Tracey, S Webber
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Psoriatic arthritis (PsA) is an immune mediated inflammatory disorder that affects 10–30% of patients with psoriasis. Ustekinumab, a monoclonal anti–IL-12/23p40 antibody, is approved for the treatment of PsA and plaque psoriasis<sup>1</sup> PSUMMIT 1 was one of two phase 3 trials of ustekinumab in adults with active PsA<sup>2</sup>In England, use of medication is subject to guidance from National Institute for Health and Care Excellence (NICE). [TA340] recommend that Ustekinumab is a possible treatment, alone or with methotrexate, for adults with active psoriatic arthritis when treatment with non-biological disease-modifying antirheumatic drugs has not worked well enough if: treatment with tumour necrosis factor (TNF) alpha inhibitors is not suitable for them, or the person has had a TNF alpha inhibitor before<sup>3</sup> We audited the survival data from our cohort of patients in district general hospital (DGH) against data from PSUMMIT trial. <h3>Objectives</h3> Our objectives were to evaluate drug survival of Ustekinumab in PsA, to compare real world data with that from PSUMMIT trial. <h3>Methods</h3> Our biologics database was searched for patients currently receiving Ustekinumab treatment for Psoriatic Arthritis and those who have had treatment failures. Length of treatment was recorded and any adverse effects which caused the treatment to be stopped. Analysis of treatment non-responders was performed including previous biologics/drug use. We then compared our results to those in the treatment arms (Ustekinumab 45mg or 90mg)of the PSUMMIT trial at week 24 and 52. <h3>Results</h3> <h3>Conclusions</h3> Ustekinumab has been shown to be a generally well tolerated drug. Our treatment group had proportionally more treatment failures than the PSUMMIT trial (4/20 20% vs 24/409 5.8%). There is the obvious criticism that our patient numbers are very small. For eligibility in PSUMMIT trial the patients had to be anti-TNF naïve. In NHS ENgland, Ustekinumab is not NICE approved as a first line agent except in certain circumstances.Therefore, our patients have had previous exposure to anti-TNF agents to which they have either been intolerant or found ineffective. More research into drug survival and persistence should be considered as real world data may not reflect RCT results. <h3>References</h3> Stelara: package insert. Horsham (PA): Janssen Biotech; 2014. McInnes IB, Kavanaugh A, Gottlieb AB, Puig L, Rahman P, Ritchlin C, et al. Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: 1 year results of the phase 3, multicentre, double-blind, placebo-controlled PSUMMIT 1 trial. Lancet 2013;382:780–9. Ustekinumab for treating active psoriatic arthritis.NICE, Technology appraisal guidance [TA340] Published date: 04 June 2015. <h3>Disclosure of Interest</h3> None declared
Combined OX40L and mTOR blockade controls effector T cell activation while preserving T <sub>reg</sub> reconstitution after transplant
Authors: Victor Tkachev, Scott N. Furlan, Benjamin Watkins, Daniel J. Hunt, Hengqi Betty Zheng, Angela Panoskaltsis-Mortari, Kayla Betz, Melanie Brown, John B. Schell, Katie Zeleski, Alison Yu, Ian Kirby, Sarah Cooley, Jeffrey S. Miller, Bruce R. Blazar, Duncan Casson, Phil Bland-Ward, Leslie S. Kean
Journal: Science Translational Medicine (2017)

A critical question facing the field of transplantation is how to control effector T cell (Teff) activation while preserving regulatory T cell (Treg) function. Standard calcineurin inhibitor-based strategies can partially control Teffs, but breakthrough activation still occurs, and these agents are antagonistic to Treg function. Conversely, mechanistic target of rapamycin (mTOR) inhibition with sirolimus is more Treg-compatible but is inadequate to fully control Teff activation. In contrast, blockade of OX40L signaling has the capacity to partially control Teff activation despite maintaining Treg function. We used the nonhuman primate graft-versus-host disease (GVHD) model to probe the efficacy of combinatorial immunomodulation with sirolimus and the OX40L-blocking antibody KY1005. Our results demonstrate significant biologic activity of KY1005 alone (prolonging median GVHD-free survival from 8 to 19.5 days), as well as marked, synergistic control of GVHD with KY1005 + sirolimus (median survival time, >100 days; P < 0.01 compared to all other regimens), which was associated with potent control of both TH/TC1 (T helper cell 1/cytotoxic T cell 1) and TH/TC17 activation. Combined administration also maintained Treg reconstitution [resulting in an enhanced Treg/Teff ratio (40% over baseline) in the KY1005/sirolimus cohort compared to a 2.9-fold decrease in the unprophylaxed GVHD cohort]. This unique immunologic signature resulted in transplant recipients that were able to control GVHD for the length of analysis and to down-regulate donor/recipient alloreactivity despite maintaining anti-third-party responses. These data indicate that combined OX40L blockade and sirolimus represents a promising strategy to induce immune balance after transplant and is an important candidate regimen for clinical translation.
THU0539 Sarcoidosis in spain: clinical and epidemiological characteristics at diagnosis in 1082 patients
Authors: R Pérez-Alvarez, B Kostov, A García González, R Gόmez De La Torre, M Lopez Dupla, B De Escalante, A Alguacil, J Chara, J Velilla, J Rascόn, JS Garcia Morillo, C Feijoo, E Fonseca, M Bonet, JL Callejas, G de la Red, E Calvo, C Soler, E Peral, JF Gόmez Cerezo, G Cruz-Caparrόs, P Perez, S Fernández Rodríguez, B Pinilla, A Gato, M Akasbi, A Robles, I Ojeda, MJ Vives, C Morcillo, M Penadés, M De Vicente, M Ramos-Casals, L Pallarés, P Brito-Zerόn
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> To characterize the main features at presentation of sarcoidosis in a large multicenter cohort from Southern Europe. <h3>Methods</h3> In January 2016, the Autoimmune Diseases Study Group (GEAS-SEMI) created a national registry (SARCOGEAS) of patients with sarcoidosis. Sarcoidosis was diagnosed in agreement with the criteria proposed by the ATS/ERS/WASOG 1999 statement, and extrathoracic disease was classified with the 2014 WASOG instrument. <h3>Results</h3> The cohort consisted of 1082 patients (82% biopsy-proven), including 618 (57%) women and 464 (43%) men, with a mean age at diagnosis of 47yrs; 140 (13%) patients were born outside Spain, 965 (89%) were White, 69 (6%) Hispanic, 30 (3%) Black/African American and 18 (2%) Asian. Thoracic involvement was present at diagnosis in 979 (90%) patients, including 437 (40%) patients with stage I, 374 (35%) with stage II, 123 (11%) with stage III and 26 (2%) with stage IV. The most frequently reported extrathoracic involvements at diagnosis were cutaneous in 385 (36%) patients, extrathoracic lymph nodes in 218 (20%), liver involvement in 151 (14%) and ocular involvement in 118 (11%). Potentially life-threatening WASOG involvements were reported in frequencies less than 10%, including neurological involvement in 77 (7%) patients, kidney involvement in 59 (5%) or cardiac involvement in 21 (2%). Therapeutic approaches at diagnosis included the use of oral glucocorticosteroids in 637 (59%) patients, immunosuppressive agents in 84 (8%, mainly methotrexate in 63 patients) and biological agents in 15 (1%, mainly infliximab in 10 cases). <h3>Conclusions</h3> In this large series of sarcoidosis from Southern Europe, clinical presentation is dominated by adenopathies (both thoracic and extrathoracic) and cutaneous involvement (erythema nodosum), with lower frequencies in the main extrathoracic involvements than that reported in US and Japanese series. <h3>Disclosure of Interest</h3> None declared
Targeting Pioglitazone Hydrochloride Therapy After Stroke or Transient Ischemic Attack According to Pretreatment Risk for Stroke or Myocardial Infarction
Authors: Walter N. Kernan, Catherine M. Viscoli, Jennifer L. Dearborn, David M. Kent, Robin Conwit, Pierre Fayad, Karen L. Furie, Mark Gorman, Peter D. Guarino, Silvio E. Inzucchi, Amber Stuart, Lawrence H. Young
Journal: JAMA Neurology (2017)

There is growing recognition that patients may respond differently to therapy and that the average treatment effect from a clinical trial may not apply equally to all candidates for a therapy. To determine whether, among patients with an ischemic stroke or transient ischemic attack and insulin resistance, those at higher risk for future stroke or myocardial infarction (MI) derive more benefit from the insulin-sensitizing drug pioglitazone hydrochloride compared with patients at lower risk. A secondary analysis was conducted of the Insulin Resistance Intervention After Stroke trial, a double-blind, placebo-controlled trial of pioglitazone for secondary prevention. Patients were enrolled from 179 research sites in 7 countries from February 7, 2005, to January 15, 2013, and were followed up for a mean of 4.1 years through the study's end on July 28, 2015. Eligible participants had a qualifying ischemic stroke or transient ischemic attack within 180 days of entry and insulin resistance without type 1 or type 2 diabetes. Pioglitazone or matching placebo. A Cox proportional hazards regression model was created using baseline features to stratify patients above or below the median risk for stroke or MI within 5 years. Within each stratum, the efficacy of pioglitazone for preventing stroke or MI was calculated. Safety outcomes were death, heart failure, weight gain, and bone fracture. Among 3876 participants (1338 women and 2538 men; mean [SD] age, 63 [11] years), the 5-year risk for stroke or MI was 6.0% in the pioglitazone group among patients at lower baseline risk compared with 7.9% in the placebo group (absolute risk difference, -1.9% [95% CI, -4.4% to 0.6%]). Among patients at higher risk, the risk was 14.7% in the pioglitazone group vs 19.6% for placebo (absolute risk difference, -4.9% [95% CI, -8.6% to 1.2%]). Hazard ratios were similar for patients below or above the median risk (0.77 vs 0.75; P = .92). Pioglitazone increased weight less among patients at higher risk but increased the risk for fracture more. After an ischemic stroke or transient ischemic attack, patients at higher risk for stroke or MI derive a greater absolute benefit from pioglitazone compared with patients at lower risk. However, the risk for fracture is also higher. clinicaltrials.gov Identifier: NCT00091949.
THU0756-HPR Predictors of fear of movement in patients with rheumatoid arthritis
Authors: GI Kinikli, H Guney, S Karahan, A Ates, M Turgay, G Kinikli
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Rheumatoid arthritis (RA) is a systemic chronic autoimmune inflammatory disease characterized by synovial joint inflammation that results in functional limitations accompanied by social and psychological outcomes. <h3>Objectives</h3> The aim of this study was to investigate the association between fear of movement and age, upper and lower extremity functions and functional disability in patients with Rheumatoid Arthritis (RA). <h3>Methods</h3> A total of 88 patients with RA participated to the study. Disease activity was assessed using the Disease Activity Score in 28 joints (DAS28). Functional disability was assessed using the Health Assessment Questionnaire-Disability Index (HAQ-DI). The Disabilities of the Arm, Shoulder and Hand Score (QuickDASH) was used to assess the upper extremity function. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used to assess the lower extremity function. The Tampa Scale for Kinesiophobia (TSK) was used to assess pain-related fear of movement. The multiple stepwise linear regression model with R-square (R<sup>2</sup>) was used to compare across the models and explain the total variance. <h3>Results</h3> Eight independent variables namely, age (r=0.215; p=0.044), QuickDASH (r=0.504; p&lt;0.001), HAQ-DI (r=0.315; p=0.003), WOMAC Pain (r=0.512; p&lt;0.001), WOMAC Stiffness (r=0.419; p&lt;0.001), WOMAC Function (r=0.398; p&lt;0.001), WOMAC Total (r=0.429; p&lt;0.001), WOMAC range (r=0.419; p&lt;0.001), demonstrated significant correlations with TSK. There were correlations between two independent variables (QuickDASH, p=0.013; WOMAC Pain, p=0.034) and TSK (R<sup>2</sup>=0.293). <h3>Conclusions</h3> Health professionals should keep in mind that fear of movement were likely to cause poorer upper extremity functional disability and lower extremity pain levels in spite of varied drug therapies in patients with RA. <h3>References</h3> Wan, S. W., He, H.-G., Mak, A., Lahiri, M., Luo, N., Cheung, P. P., &amp; Wang, W. (2016). Health-related quality of life and its predictors among patients with rheumatoid arthritis. Applied Nursing Research, 30, 176–183. Doury-Panchout, F., Metivier, J., &amp; Fouquet, B. (2015). Kinesiophobia negatively influences recovery of joint function following total knee arthroplasty. European journal of physical and rehabilitation medicine, 51(2), 155–161. <h3>Disclosure of Interest</h3> None declared
Kinetics and biomarkers of severe cytokine release syndrome after CD19 chimeric antigen receptor–modified T-cell therapy
Authors: Kevin A. Hay, Laïla-Aïcha Hanafi, Daniel Li, Juliane Gust, W. Conrad Liles, Mark M. Wurfel, José A. López, Junmei Chen, Dominic Chung, Susanna Harju-Baker, Sindhu Cherian, Xueyan Chen, Stanley R. Riddell, David G. Maloney, Cameron J. Turtle
Journal: Blood (2017)
FRI0237 Safety of biosimilar infliximab use in a medical day hospital: a case-series
Authors: JM Lopez Suarez, JM Lopez Chozas, E Rubio Romero
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The first biosimilar anti-NTF (infliximab) approved by the EMA (European Medicines Agency) began to be used throughout Europe in 2015. Since then, it has been widely used throughout the world, even replacing the original treatment approved in 1999 Remicade® with Remsima®, a biosimilar drug. This medicine is currently approved to treat people who have been diagnosed with rheumatoid arthritis, ankylosing spondylitis or psoriatic arthritis in the field of reheumatology, in addition to ulcerative colitis (UC) or Crohn9s disease (EC) in gastroenterology. However, safety data of the use of Remsima® infliximab in a medical day hospital (MDH) are lacking. <h3>Objectives</h3> To report intrainfusion and postinfusion adverse events related to intravenous Remsima® use in a medical day hospital. Besides, we will describe the rehospitalizations and continuity of treatment in the follow up. <h3>Methods</h3> We designed a prospective uncontrolled case-series study. Patients referred from March 2015 to October 2016 to our MDH to receive intravenous Remsima® were consecutively enrolled. Demographic data were collected, and a harmonised active monitoring strategy was applied. We recorded the indication for treatment, the doses administered and the number and symptoms of acute transfusion reactions (ATR) occurring both in the infusion period and during the 3 hour postinfusion observation interval <h3>Results</h3> 2828 doses were administered, 0.67% presented ATR, all of them during the infusion and reported to the Regional Pharmacovigilance Center. 53% of those ATR were women and they were on average 35.78 years (SD 14.71). The mean dose used was 4,809 mg/kg (SD 0.47). The indications for treatment in patients suffering ATR were: EC (47%), CU (26%), Spondylitis (21%) and Psoriasis (5%). As a predominant symptom during ATR we found: shortness of breath (36.89%), pruritus (15.75%), flushing sensation (15.75%), urticaria (10.4%), alopecia (5.2%), chest pain (5.2%), paresthesia (5.2%) and nausea (5.2%). 95% of ATR showed complete recovery of the symptoms, 47% disappeared with the pause of infusion. However, they had prolonged in MDH stay, the infusion was stopped for 30 minutes and restarted at a lower rate according to the protocol. 21% of patients presenting ATR dropped out because of the symptomatology, which represents 0.14% of the total infusions. <h3>Conclusions</h3> Biosimilar Inflliximab seems to be safe in a MDH setting, given the low rate of adverse transfusion reactions during the 18 months analyzed. The most frequent adverse reaction was shortness of breath. <h3>Disclosure of Interest</h3> None declared
THU0506 Association of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, platelet indices and serum amyloid a levels in children with familial mediterranean fever
Authors: F Dörtbaş, E Comak, E Isıyel
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Familial mediterranean fever (FMF) is an autosomal recessive, inherited, autoinflammatory disease characterized by recurrent, self-limited bouts of fever and inflammation. Persistent subclinical inflammation was related to increased risk of developing the serious complications, such as life- threatening amyloid a (AA) amyloidosis. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and platelet indices [mean platelet volume (MPV) and platelet distribution width (PDW)] are simple, inexpensive, and useful markers to determine inflammation. Although, there have been a lots of data regarding inflammatory markers in FMF, little information was available the relationship between NLR, PLR, MPV and serum amyloid A levels. <h3>Objectives</h3> The aim of this study was to investigate association of NLR, PLR, platelet indices and serum amyloid A levels in children with FMF <h3>Methods</h3> The medical records of children with FMF were reviewed retrospectively. Information including demographic features, clinical and laboratory findings, SAA and C-reactive protein (CRP) levels, type of MEFV mutation were collected from the hospital9s computerized database following approval by the local ethics commitee. The NLR and PLR were calculated from a complete blood count. Children (&lt;7 years old) was excluded from study due to age related features of neutrophil-to-lymphocyte ratio. <h3>Results</h3> Our study group included 127 children (60 males, 67 females) with FMF, diagnosed according to the Turkish pediatric FMF criteria. Their mean age was 11.35±3.69 years, their mean age at time of disease onset was 8.73±3.93 years, and their mean follow up period was 28.32±2.90 months. Thirty two children (25.2%) were homozygous, 56 children (44.0%) were compound heterozygous and 39 children (30.7%) were heterozygous for MEFV gene. In study population, the mean SAA levels, C-reactive protein (CRP) levels and er<i>ythrocyte</i> sedimentation rate (ESR) were 9.21±13.88 mg/L, 1.38±2.31 mg/dl and 16.64±12.59 mm/hour, respectively. Significant positive correlations were found between SAA, ESR, CRP and NLR (r=0.2, p=0.02; r=0.28, p=0.001; r=0.32, p=0.001, respectively). Hovewer, we did not find any significant correlation between SAA, ESR, CRP and platelet indices (MPV, PDW) and PLR (all p&gt;0.05). <h3>Conclusions</h3> Our finding suggest that simply calculating NLR from complete blood count may be used as an additional indicator of inflammation in children with FMF. But, platelet indices and PLR cannot be used as a laboratory markers predicting inflammation in these children. <h3>Disclosure of Interest</h3> None declared
Effect of Climatic Environment Upon the Genesis of Subcutaneous Tumors Induced by Methylcholanthrene and Upon the Growth of a Transplantable Sarcoma in C3H Mice&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn2"&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/xref&gt;
Authors: Edward W. Wallace, Helene M. Wallace, Clarence A. Mills
Journal: JNCI Journal of the National Cancer Institute (1942)

Effect of Climatic Environment Upon the Genesis of Subcutaneous Tumors Induced by Methylcholanthrene and Upon the Growth of a Transplantable Sarcoma in C3H Mice Edward W. Wallace, Edward W. Wallace associate professor of pharmacology Search for other works by this author on: Oxford Academic PubMed Google Scholar Helene M. Wallace, Helene M. Wallace research associate Search for other works by this author on: Oxford Academic PubMed Google Scholar Clarence A. Mills Clarence A. Mills professor of experimental medicine College of Medicine, University of Cincinnati Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 3, Issue 1, August 1942, Pages 99–110, https://doi.org/10.1093/jnci/3.1.99 Published: 01 August 1942
FRI0191 Incidence of disease worsening in inflammatory arthritis patients on long-term innovator infliximab therapy
Authors: AM Marrache, E Psaradellis, J Vaillancourt, E Rampakakis, F Nantel
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> A recent randomized controlled study in a single country reported rates of disease worsening over a one-year follow-up period for innovator infliximab (REMICADE®, IFX) and a comparator in various diseases including AS and RA. After a mean duration of treatment of 6.7 years of innovator IFX, rates for disease worsening post-one year follow-up were 39.5% in AS and 36.7% in RA<sup>1</sup>. Other such data reporting disease worsening rates are rare. <h3>Objectives</h3> Using data from a longitudinal database, the objective was to determine the incidence of disease worsening in AS and RA patients on long-term therapy with innovator IFX. PsA patients were not included in this study due to low numbers (n=49). <h3>Methods</h3> BioTRAC is an ongoing, prospective registry of inflammatory arthritis patients initiating treatment with infliximab, golimumab or ustekinumab that has been ongoing since 2002 in Canada. We included AS and RA patients who had been on innovator IFX therapy for at least two, four or six years. Disease worsening endpoint was defined as follows: for AS patients; an increase in ASDAS ≥1.1 from baseline and a minimum score of 2.1. For RA patients; an increase in DAS28 ≥1.2 from baseline and a minimum score of 3.2. <h3>Results</h3> This analysis included a total of 196 AS and 425 RA patients. Among AS patients, 36.1% were female, 90.8% were bio-naïve at IFX initiation and 50% were on concomitant NSAID(s) at the 2-year index. The mean (SD) ASDAS score was 2.17 (1.05). As for the RA patients, 75% were female, 88.5% were bio-naïve, and 93% were on concomitant DMARD(s) while 35% were on corticosteroids at the 2-year index. The mean (SD) DAS28 ESR and DAS 28 CRP were 3.37 (1.40) and 3.00 (1.24), respectively. As shown in table 1, the incidence of disease worsening in AS and RA patients on stable IFX for 2–6 years was low and varied from 2.7% to 11.5% at the subsequent 12 and 24 months visit. <h3>Conclusions</h3> In this prospective longitudinal cohort, patients on long-term innovator IFX therapy show low rates of disease worsening of 2.7% to 11.5% at 1 and 2 years in AS and RA. Additional studies may elucidate the true rate of and reasons for disease worsening in rheumatologic populations. <h3>References</h3> Goll et al. Biosimilar Infliximab (CT-P13) Is Not Inferior to Originator Infliximab: Results from a 52-Week Randomized Switch Trial in Norway. Arthritis Rheum 2016;68(S10). Abstract 19L. <h3>Disclosure of Interest</h3> A. M. Marrache Employee of: Janssen Inc., E. Psaradellis Employee of: JSS Medical Research, J. Vaillancourt Employee of: JSS Medical Research, E. Rampakakis Employee of: JSS Medical Research, F. Nantel Employee of: Janssen Inc.