POS0631 COMPARATIVE EFFICACY OF COMBINATION THERAPY WITH BIOLOGIC OR TARGET SYNTHETIC DRUGS FOR RHEUMATOID ARTHRITIS: A BAYESIAN NETWORK META-ANALYSIS

Background:Biologic agents and small molecules have shown long term benefit when added in patients with active RA non-responders to conventional DMARDs treatment (1). In head-to-head trials only adalimumab was compared to other drugs in combination with methotrexate, with some evidence of superiority but no data on multiple comparisons have been reported (2). The availability of biosimilar agents led in clinical practice to prefer mainly the cheaper one, so the choice of the most effective treatment remains a clinical unmet need (3).Objectives:To assess the relative efficacy of different therapeutic strategies for achieving ACR50 response at 24 weeks of treatment in patients with active RA, based on direct and indirect evidence.Methods:We performed systematic reviews of MEDLINE, EMBASE, and Cochrane Library databases, searching for all published phase 3 Randomised Controlled Trials (RCTs) comparing adalimumab originator to its biosimilars, abatacept, baricitinib, certolizumab pegol, tofacitinib or upadacitinib, combined to MTX, in patients with active RA inadequate responders to previous conventional DMARDs. American College of Rheumatology (ACR) 50% response at 24 weeks of treatment had to be evaluated both in adalimumab branch and in examined drug branch. Bayesian fixed-effect network meta-analysis was performed to combine the direct and indirect evidence using the WinBUGS 1.4 software (MRC Biostatistics Unit, Cambridge, UK).Results:Eleven RCTs evaluating 6'004 patients were included in the analysis, namely originator (1) and biosimilars (2) adalimumab, abatacept (3), baricitinib (4), certolizumab pegol (5), tofacitinib (6) and upadacitinib (7). Convergence was reached at n.100'000 iterations. Upadacitinib seems to be more effective than both originator and biosimilar adalimumab in achieving ACR 50 (OR 1.65 95% CI 1.25-2.14 and OR 1.22 95%CI 1.10-2.18; see Figure 1). Similarly, tofacitinib was more effective of originator adalimumab (OR 1.25 95%CI 1.01-155). Upadacitinib was ranked first among treatments with a probability of being the agent more likely to induce ACR 50 response of 86.3%. In this regard tofacitinib had a probability of 4.8%, hence it was ranked second among treatments.Figure 1.Caterpillar plot OR for ACR50 at 24 weeks (originator [1] and biosimilars [2] adalimumab; abatacept [3]; baricitinib [4]; certolizumab pegol [5]; tofacitinib [6]; upadacitinib [7]).Conclusion:Although patients with active RA and inadequate response to MTX have different therapeutic combination of biologics or small molecules options, the best relative efficacy in terms of ACR50 response after 24 weeks of treatment is for upadacitinib 15 mg/day.References:[1]Smolen JS, et al. Annals of the Rheumatic Diseases 2020;79:685-699.[2]Combe B, Lukas C. Joint Bone Spine, 2020,105004.[3]Caporali R, et al. Biomed Res Int. 2018 Sep 9;2018:3878953.Disclosure of Interests:Fabio Cacciapaglia Speakers bureau: Roche, Pfizer, Eli Lilly, MSD, UCB, BMS, Abbvie, Vincenzo Venerito: None declared, Stefano Stano: None declared, Marco Fornaro: None declared, Giuseppe Lopalco Speakers bureau: Celgene, BMS, Abbvie, Novartis, Florenzo Iannone Speakers bureau: Roche, Pfizer, Eli Lilly, MSD, UCB, BMS, Abbvie, Novartis, Celgen

Bosonic Seesaw in the Unparticle Physics

Recently, conceptually new physics beyond the Standard Model has been proposed by Georgi, where a new physics sector becomes conformal and provides "unparticle" which couples to the Standard Model sector through higher dimensional operators in low energy effective theory. Among several possibilities, we focus on operators involving the (scalar) unparticle, Higgs and the gauge bosons. Once the Higgs develops the vacuum expectation value (VEV), the conformal symmetry is broken and as a result, the mixing between the unparticle and the Higgs boson emerges. In this paper, we consider a natural realization of bosonic seesaw in the context of unparticle physics. In this framework, the negative mass squared or the electroweak symmetry breaking vacuum is achieved as a result of mass matrix diagonalization. In the diagonalization process, it is important to have zero value in the (1,1)-element of the mass matrix. In fact, the conformal invariance in the hidden sector can actually assure the zero of that element. So, the bosonic seesaw mechanism for the electroweak symmetry breaking can naturally be understood in the framework of unparticle physics.Comment: 5 pages, no figure; added one more referenc

The Gaugephobic Higgs

We present a class of models that contains Randall-Sundrum and Higgsless models as limiting cases. Over a wide range of the parameter space WW scattering is mainly unitarized by Kaluza-Klein partners of the W and Z, and the Higgs particle has suppressed couplings to the gauge bosons. Such a gaugephobic Higgs can be significantly lighter than the 114 GeV LEP bound for a standard Higgs, or heavier than the theoretical upper bound. These models predict a suppressed single top production rate and unconventional Higgs phenomenology at the LHC: the Higgs production rates will be suppressed and the Higgs branching fractions modified. However, the more difficult the Higgs search at the LHC is, the easier the search for other light resonances (like Z', W', t', exotic fermions) will be.Comment: 20 pages, 3 figure

Finite Gluon Fusion Amplitude in the Gauge-Higgs Unification

We show that the gluon fusion amplitude in the gauge-Higgs unification scenario is finite in any dimension regardless of its nonrenormalizability. This result is supported by the fact that the local operator describing the gluon fusion process is forbidden by the higher dimensional gauge invariance. We explicitly calculate the gluon fusion amplitude in an arbitrary dimensional gauge-Higgs unification model and indeed obtain the finite result.Comment: 15 pages, final version to appear in MPL

Temporal Control of the Host-Guest Properties of a Calix[6]arene Receptor by the Use of a Chemical Fuel

The host-guest interaction of a 1,3,5-trisaminocalix[6]arene receptor with N-methylisoquinolinium trifluoromethanesulfonate (Kassof 500 ± 30 M-1in CD2Cl2) can be dissipatively driven by means of 2-cyano-2-(4′-chloro)phenylpropanoic acid used as a convenient chemical fuel. When the fuel is added to a dichloromethane solution containing the above complex, the host is induced to immediately release the guest in the bulk solution. Consumption of the fuel allows the guest to be re-uptaken by the host. The operation can be satisfactorily reiterated with four subsequent additions of fuel, producing four successive release-reuptake cycles. The percentage of the guest temporarily released in the bulk solution by the host and the time required for the reuptake process can be finely regulated by varying the quantities of added fuel

On the presentation of the LHC Higgs Results

We put forth conclusions and suggestions regarding the presentation of the LHC Higgs results that may help to maximize their impact and their utility to the whole High Energy Physics community.Comment: Conclusions from the workshops "Likelihoods for the LHC Searches", 21-23 January 2013 at CERN, "Implications of the 125 GeV Higgs Boson", 18-22 March 2013 at LPSC Grenoble, and from the 2013 Les Houches "Physics at TeV Colliders" workshop. 16 pages, 3 figures. Version 2: Comment added on the first publication of signal strength likelihoods in digital form by ATLA

SAT0092 CARDIOVASCULAR RISK ASSESSMENT IN PATIENTS WITH AUTOIMMUNE RHEUMATIC DISEASES: AN ITALIAN RHEUMATOLOGISTS' SURVEY

Background:Cardiovascular (CV) disease is the leading cause of morbidity and mortality in patients with inflammatory arthritis. The growing attention to the CV risk characterizing patients with autoimmune inflammatory disease led EULAR to provide recommendations on CV risk management (1). To date, there are no data on the adherence to EULAR recommendation among Italian rheumatologists.Objectives:Our objective was to measure the level of awareness and the attitude to manage CV risk.Methods:Italian rheumatologists were invited to anonymously answer a web-based questionnaire designed by the steering committee of the Cardiovascualr and Obesity in Rheumatic Diseases (CORDIS) study group of the Italian Society of Rheumatology. The first part of the questionnaire concerned demographic information; the subsequent questions concerned the attitude to assess CV risk and the limitations for not assessing, the specific CV risks considered in the clinical practice and their management. Data are presented using standard summary statistics and were expressed as mean+/-standard deviation or median (interquartile range) according to variables' distribution.Results:One thousand-three hundred rheumatologists (of whom 500 are under 40 and 100 over 70 years of age) have been invited by email to complete the survey. The questionnaire has been filled by 102 rheumatologists (7.85%) (53 females and 49 males) with a median age of 38 years (32-48) and a median of 4 (0-15) years of specialization. Most of the physician who answered the questionnaire works in University Hospitals (67/102; 65.7%), 22 out of 102 (21.6%) in non-academic Hospitals, and the remaining 12,7% in territorial outpatient clinics.When asked if they usually evaluate CV risk in patients with autoimmune rheumatic diseases, 67/102 (67.2%) answered positively, 18 no (17.6%) and 7 did not answer the question; 82% of those who routinely assess the CV do it by themselves. The barriers limiting the assessment of CV risk included: i) lack of time (79%); ii) complex management (12%); inadequate training (9%).As for the CV risk factors, lipid profile, hypertension and diabetes are assessed by most of the rheumatologists (90%, 89% and 88%, respectively), family history by 78% and body mass index by 75.3% and waist circumference only by 25% of those who completed the survey.Finally, only 18.6% stated that they manage by themselves CV risk in patients with autoimmune rheumatic diseases while 50% refer patients to other specialists and 23.4% to general practitioner.Conclusion:Despite the growing awareness on the CV risk characterizing patients with autoimmune rheumatic disease, about one third of young Italian rheumatologists does not strictly adhere to the EULAR recommendations on CV management, mostly due to insufficient time during the routine care visits.References:[1] Agca R et al. Ann Rheum Dis 2017; 76: 17-28.Disclosure of Interests:Francesca Romana Spinelli Grant/research support from: Pfizer, Speakers bureau: Lilly, BMS, Celgene, Fabio Cacciapaglia Speakers bureau: BMS; Roche; Pfizer; Abbvie, Fabiola Atzeni: None declared, Gianluca Erre: None declared, Andreina Manfredi: None declared, Elena Bartoloni Bocci: None declared, Matteo Piga: None declared, Garifallia Sakellariou Speakers bureau: Abbvie, Novartis, MSD, Ombretta Viapiana: None declared, Elisa Gremese Speakers bureau: Abbvie, BMS, Celgene, Jannsen, Lilly, MSD, Novartis, Pfizer, Sandoz, UC

Alexithymia and immunoendocrine parameters in patients affected by systemic lupus erythematosus and rheumatoid arthritis

Objective: Aim of this study was to evaluate the prevalence of alexithymia in patients affected by SLE or RA and to investigate the correlation between alexithymia and immunoendocrine parameters (PRL, hGH, IL-6 and TNF-alfa). Methods: Twenty-five patients (12 and 13 affected by SLE and RA, respectively) were enrolled into the study. The Toronto Alexithymia Scale-20 (TAS-20) was administered. PRL, hGH, IL-6 and TNF-alfa levels were measured by commercially available ELISA kits. Results: Alexithymia prevalence (TAS-20≥51) was 54% in RA and 42% in SLE patients. hGH serum levels were 3.1±4.2 and 1.1±0.9 IU/ml in SLE and RA, respectively. PRL concentration was 18.4±6.5 ng/ml and 14.2±4.0 ng/ml in SLE and RA patients, respectively (p=0.03). In RA group, TNF-alpha was 20±36.2 whereas in SLE it was 4.9±12.8 pg/ml (p=0.03); IL-6 serum concentrations were 24.4±25.1 and 2.9±5.4 pg/ml, in RA and SLE respectively (p=0.004). The serum level of hGH showed slight increase in alexithymic group (A) compared to non alexithymic group (NA) in both SLE and RA patients. PRL serum levels in SLE-A patients was 26.7±17.3 ng/ml while in SLE-NA patients was 12.4±3.3 ng/ml (p=0.04). In RA patients increased values of IL-6 and TNF-alpha were present in the A group compared to NA group (IL-6: 35.3±28 pg/mL vs 3.5±3.9 pg/mL, p=0.01; TNF-alpha: 34.7±39 pg/mL vs 3.1±3.4 pg/mL, p=0.01). Conclusions: In this preliminary results we found an high prevalence of alexithymia and a correlation between immunoendocrine parameters and alexhytimic features in SLE and RA, suggesting that an immunomodulatory pathway could influence this cognitive style in patients with autoimmune disorders. Other studies should contribute to find a common biological pathway linking alexithymia and autoimmunity

A clean signal for a top-like isosinglet fermion at the Large Hadron Collider

We predict a clean signal at the Large Hadron Collider ($\sqrt s)$=14 TeV for a scenario where there is a top-like, charge +2/3 vectorlike isosinglet fermion. Such a quark, via mixing with the standard model top, can undergo decays via both flavour-changing Z-boson coupling and flavour-changing Yukawa interactions. We concentrate on the latter channel, and study the situation where, following its pair-production, the heavy quark pair gives rise to two tops and two Higgs boson. We show that the case where each Higgs decays in the $b\bar{b}$ channel, there can be a rather distinct and background-free signal that can unveil the existence of the vectorlike isosinglet quark of this kind.Comment: 14 pages, 5 figures, 4 table