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Background The Calcium Pyrophosphate Deposition (CPPD) subgroup of the Outcome Measures in Rheumatology (OMERACT) Ultrasound working group was established to validate ultrasound as an outcome measure instrument for CPPD, and in 2017 has developed and validated standardised definitions for elementary lesions for the detection of calcium pyrophosphate crystals in joints. The aim of this study was to develop and evaluate the reliability of a consensus -based ultrasound scoring system for CPPD extent, representing the next phase in the OMERACT methodology.Methods In this study the novel scoring system for CPPD was developed through a stepwise process, following an established OMERACT ultrasound methodology. Following a previous systematic review to gather available evidence on existing scoring systems for CPPD, the novel scoring system was developed through a Delphi survey based on the expert opinion of the members of the OMERACT Ultrasound working group-CPPD subgroup. The reliability of the scoring system was then tested on a web-based and patient-based exercise. Intra-reader and inter-reader reliability of the new scoring system was assessed using weighted Light's K coefficients.Findings The four-grade semiquantitative scoring system consisted of: grade 0 (no findings consistent with CPPD), grade 1 (& LE;3 single spots or 1 small deposit), grade 2 (>3 single spots or >1 small deposit or & GE;1 larger deposit occupying & LE;50% of the structure under examination in the reference image-ie, the scanning view with the highest grade of depositions), and grade 3 (deposits that occupy more than 50% of the structure under examination in the reference image). The score should be applied to the knee (menisci and hyaline cartilage) and the triangular fibrocartilage complex of the wrist. The intra-reader and inter-reader reliabilities on static images were almost perfect (K 0 & BULL;90 [95% CI 0 & BULL;79-1 & BULL;00] and K 0 & BULL;84 [0 & B

Biological drugs, such as proteins and immunogens, are increasingly used to treat various diseases, including tumors and autoimmune diseases, and biological molecules have almost completely replaced synthetic drugs in rheumatology. Although biological treatments such as anti-tumor necrosis factor (TNF) drugs seem to be quite safe, they cause some undesirable effects, such as the onset of infections due to weakening of the immune system. Given the biological nature of these drugs, they might be recognized as extraneous; this would induce an immune reaction that neutralizes their effectiveness or lead to more serious consequences. Laboratories play a pivotal role in appropriate therapeutic management. The aim of this review was to underline the production of anti-drug antibodies during treatment with biological drugs and highlight the role of laboratories in ensuring appropriate use of these drugs.

Maurizio Benucci,1 Arianna Damiani,2 Francesca Li Gobbi,1 Valentina Grossi,3 Maria Infantino,3 Mariangela Manfredi,3 Laura Niccoli,4 Fabrizio Cantini4 1Rheumatology Unit, Hospital S. Giovanni di Dio, Azienda USL-Toscana Centro, Florence, Italy; 2Rheumatology Unit, University of Florence, Florence, Italy; 3Immunology and Allergology Laboratory Hospital S. Giovanni di Dio, Azienda USL-Toscana Centro, Florence, Italy; 4Rheumatology Unit, S. Stefano Hospital, Azienda USL-Toscana Centro, Prato, ItalyCorrespondence: Maurizio BenucciRheumatology Unit, Azienda Sanitaria USL-Toscana Centro, Hospital S. Giovanni di Dio, Via Torregalli 3, Florence 50143, ItalyTel +39-055-6932636Fax +39-055-6932099Email maurizio.benucci@uslcentro.toscana.itAbstract: Over the last 20 years, the greatly improved knowledges of underlying pathogenic mechanisms of AS, including the role of tumor necrosis factor (TNF), the interleukin 23/Th17 axis, and interleukin-17 (Il-17), constituted the rationale to develop biologics selectively inhibiting these pathways. For more than 10 years, anti-TNF biologics were successfully employed to treat AS, with marked improvement of signs and symptoms in around 60% of the patients. Recent knowledge of the pathophysiology of spondyloarthritis has highlighted the emerging role of the IL-17/IL-23 axis. New therapies with selective biological drugs have emerged in the treatment of this pathology. In this review, we evaluated the effects of ixekizumab, a new anti–IL-17A, that was licensed both by EMA and FDA in August 2019 for the treatment of ankylosing spondylitis. The review highlights the efficacy and safety data of the 3 randomized controlled trials (COAST V-COAST W-COAST X) and those of the extension to 52 weeks of COAST V and COAST W.Keywords: ixekizumab, ankylosing spondylitis, randomized control trials

Maurizio Benucci,1 Arianna Damiani,1 Mariangela Manfredi,2 Maria Infantino,2 Valentina Grossi,2 Francesca Li Gobbi11Rheumatology Unit, S.Giovanni di Dio Hospital, Florence, Italy; 2Immunology and Allergology Laboratory Unit, S.Giovanni di Dio Hospital, Azienda USL-Toscana Centro, Florence, ItalyAbstract: Rheumatoid arthritis (RA) is a chronic inflammatory disorder that affects joints with swelling and progressive joint destruction. The pathology leads to a progressive disability with an impact on the quality of life of the patients. Strategies to reduce in-patient care costs could have a considerable impact on lowering the direct medical costs of RA in Italy. Abatacept, a selective T-cell costimulation modulator, is a valuable treatment option for patients with moderate-to-severe RA. A search using the keywords “cost-effectiveness analysis", "budget impact model", "abatacept", and "rheumatoid arthritis” was carried out on PubMed. Abatacept in the first- and second-treatment lines has been evaluated in our research. We evaluated patients with inadequate MTX response, inadequate anti-TNF agents response, switch studies and real-world data. Furthermore, in our research, we evaluated the main head-to-head studies published.Keywords: abatacept, budget impact model, cost-effectiveness analysis, rheumatoid arthritis

Maurizio Benucci,1 Francesca Bandinelli,1 Arianna Damiani,1 Francesca Li Gobbi,1 Maria Infantino,2 Valentina Grossi,2 Mariangela Manfredi2 1Rheumatology Unit, Hospital S. Giovanni di Dio, Azienda USL-Toscana Centro, Florence, Italy; 2Immunology and Allergology Laboratory Unit, Hospital S. Giovanni di Dio, Azienda USL-Toscana Centro, Florence, Italy Background: Rheumatoid arthritis patients are exposed to a high risk of cardiovascular morbidity and mortality even in the early phases of the disease. Methods: We evaluated carotid common carotid intimal media thickness (ccIMT) intimal thickness and brachial flow-mediated dilation (FMD) of 45 rheumatoid arthritis patients without known cardiovascular risk factors or heart disease on a stable dose of prednisone 5.2±1.2 mg/day and Methotrexate 11.5±2.1 mg at baseline (T0) and after 12 months (T1) of treatment with Abatacept 125 mg/week. The comparison between T0 and T1 (t- and Mann–Whitney test), correlation (Spearman r), and predictivity (linear regression) of FMD, ccIMT vs clinical and laboratory parameters (disease activity 28 score, tumor necrosis factor alpha [TNFα], interleukin-6, erythrocyte sedimentation rate, C-reactive protein (CRP), CD3+, CD3+/CD4+, CD3+/CD8+, CD19+(B), CD20+(B), NK CD3-CD56+CD16+, CD14+ HLA DR+, CD4+CD28+, CD4+CD28, rheumatoid factor IgM, IgA, RF IgG, anti-citrullinated peptide antibodies) were also evaluated. Results: During Abatacept treatment, ccIMT and FMD remained stable and disease activity 28 score, CRP, erythrocyte sedimentation rate, and interleukin-6 decreased significantly (p=0.0001, 0.002, 0.0002, 0.0001 respectively). At T0, only ccIMT resulted as correlated with baseline TNFα values (p=0.0245) in an inverse proportion. At T1, ccIMT correlated with CD3/CD8+ lymphocytes number (p=0.0351) and FMD with CRP (p=0.0075). In regression analysis, baseline ccIMT and FMD had a low predictivity for TNFα (p=0.011) and CRP (p=0.049)

Maurizio Benucci,1 Arianna Damiani,1 Francesca Li Gobbi,1 Francesca Bandinelli,1 Maria Infantino,2 Valentina Grossi,2 Mariangela Manfredi,2 Guillaume Noguier,3 Francesca Meacci2 1Rheumatology Unit, 2Immunology and Allergology Laboratory Unit, USL-Toscana Centro, Hospital S. Giovanni di Dio, Florence, Italy; 3Theradiag, Croissy Beaubourg, France Introduction: The aim of this study was to investigate the correlation between human leukocyte antigen (HLA) haplotypes and the development of antidrug antibodies (ADAs) in a cohort of patients with rheumatic diseases.Patients and methods: We evaluated the presence of ADAs in 248 patients with inflammatory rheumatic diseases after 6 months of treatment with anti-TNF drugs: 26 patients were treated with infliximab (IFX; three with rheumatoid arthritis [RA], 13 with ankylosing spondylitis [AS], 10 with psoriatic arthritis [PsA]); 83 treated with adalimumab (ADA; 24 with RA, 36 with AS, 23 with PsA); 88 treated with etanercept (ETA; 35 with RA, 27 with AS, 26 with PsA); 32 treated with certolizumab (CERT; 25 with RA, two with AS, five with PsA); and 19 treated with golimumab (GOL; three with RA, seven with AS, nine with PsA). Serum drug and ADA levels were determined using Lisa-Tracker Duo, the ADA-positive samples underwent an inhibition test, and the true-positive samples underwent genetic HLA typing. To have a homogeneous control population, we also performed genetic HLA typing of 11 ADA-negative patients.Results: After inhibition test, the frequency of ADAs was 2/26 patients treated with IFX (7.69%), 4/83 treated with ADA (4.81%), 0/88 treated with ETA (0%), 4/32 treated with CERT (12.5%), and 1/19 treated with GOL (5.26%). The frequency of HLA alleles in the examined patients was HLA-DRβ-11 0.636, HLA-DQ-03 0.636, and HLA-DQ-05 0.727. The estimated relative risks between the ADA-positive patients and the ADA-negative patients were HLA-DRβ-11 2.528 (95% CI 0.336–19.036), HLA-DQ-03 1.750 (95% CI 0.

Maurizio Benucci,1 Roberto Ravasio,2 Arianna Damiani1 1Rheumatology Unit, S. Giovanni di Dio Hospital, Florence, 2Health Publishing & Services Srl, Milan, Italy Introduction: Biological disease-modifying antirheumatic drugs are particularly recommended for use in patients who are poor responders, are intolerant to conventional disease-modifying antirheumatic drugs (cDMARDs), or in whom continued treatment with cDMARDs is deemed inappropriate. We estimated the efficacy and treatment costs associated with the use of tocilizumab (TCZ) plus methotrexate (Mtx) versus abatacept (ABT) plus Mtx in the treatment of rheumatoid arthritis (RA) in patients previously treated with Mtx. Methods: Clinical data from a Technology Appraisal Guidance published in January 2016 by the National Institute for Health and Care Excellence were used. Pharmacoeconomic comparison between biological agents was carried out to estimate the respective cost for the number needed to treat (NNT) compared to cDMARDs using both American College of Rheumatology (ACR) and European League against Rheumatism (EULAR) criteria. A 6-month period was considered. Direct medical costs including pharmacological therapy, administration, and monitoring were considered. Results: Using both ACR and EULAR criteria, TCZ subcutaneously (sc) or intravenously (iv) had a lower NNT (higher efficacy) compared to ABT (iv/sc). The most significant differences in favor of TCZ were observed using EULAR criteria. Related to the level of efficacy observed, TCZ (iv/sc) had a lower cost for NNT with both ACR and EULAR criteria compared to ABT (iv/sc). Sensitivity analysis confirmed these results. Conclusion: TCZ (iv/sc) represents a more cost-effective option than ABT (iv/sc) in the treatment of RA in patients previously treated with Mtx. Keywords: ACR, EULAR, pharmacoeconomics, rheumatology, economic, bDMARDs