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Objective Randomized controlled trials (RCTs) in biologic-naïve rheumatoid arthritis (RA) patients with high disease activity and inadequate response/intolerance to methotrexate have shown interleukin-6 (IL-6) receptor inhibitors (IL-6Ri) to be superior to tumor necrosis factor inhibitors (TNFi) as monotherapy. This observational study aimed to compare the effectiveness of TNFi vs IL-6Ri as mono- or combination therapy in biologic/targeted synthetic (b/ts) -experienced RA patients with moderate/high disease activity. Methods Eligible b/ts-experienced patients from the CorEvitas RA registry were categorized as TNFi and IL-6Ri initiators, with subgroups initiating as mono- or combination therapy. Mixed-effects regression models evaluated the impact of treatment on Clinical Disease Activity Index (CDAI), patient-reported outcomes, and disproportionate pain (DP). Unadjusted and covariate-adjusted effects were reported. Results Patients initiating IL-6Ri (n = 286) vs TNFi monotherapy (n = 737) were older, had a longer RA history and higher baseline CDAI, and were more likely to initiate as third-line therapy; IL-6Ri (n = 401) vs TNFi (n = 1315) combination therapy initiators had higher baseline CDAI and were more likely to initiate as third-line therapy. No significant differences were noted in the outcomes between TNFi and IL-6Ri initiators (as mono- or combination therapy). Conclusion This observational study showed no significant differences in outcomes among b/ts-experienced TNFi vs IL-6Ri initiators, as either mono- or combination therapy. These findings were in contrast with the previous RCTs in biologic-naïve patients and could be explained by the differences in the patient characteristics included in this study. Further studies are needed to help understand the reasons for this discrepancy in the real-world b/ts-experienced population. Key Points• Patients with rheumatoid arthritis (RA) often require switching between biologics or targeted synthetic (b/ts) disease-modifying anti-rheumatic drugs (DMARDs) to achieve their treatment target.• Head-to-head randomized controlled trials (RCTs) in biologic-naïve RA patients with high disease activity and inadequate response/intolerance to methotrexate have shown interleukin-6 receptor inhibitors (IL-6Ri) to be superior to tumor necrosis factor inhibitors (TNFi) as monotherapy; however, there are no RCTs comparing these therapies in a population previously treated with b/tsDMARDs (i.e., b/ts-experienced patients).• This observational study compared the effectiveness of TNFi vs IL-6Ri (as mono- or combination therapy) in b/ts-experienced RA patients with moderate or high disease activity and found no significant differences in clinical outcomes for the two treatments.• A discrepancy is noted between our study and RCTs, which have shown superiority of IL-6Ri therapy (albeit in biologic-naïve patients). Further analyses may help elucidate the reason for this discrepancy in the real-world b/ts-experienced population.

ObjectivesThis study evaluated the comparative effectiveness of a tumour necrosis factor inhibitor (TNFi) versus a non-TNFi (biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs)) as the first-line treatment following conventional synthetic DMARDs, as well as potential modifiers of response, observed in US clinical practice.MethodsData were from a large US healthcare registry (Consortium of Rheumatology Researchers of North America Rheumatoid Arthritis Registry). The analysis included patients (aged ≥18 years) with a documented diagnosis of rheumatoid arthritis (RA), a valid baseline Clinical Disease Activity Index (CDAI) score of >2.8 and no prior bDMARD or tsDMARD use. Outcomes were captured at 1-year postinitiation of a TNFi (adalimumab, etanercept, certolizumab pegol, golimumab or infliximab) or a non-TNFi (abatacept, tocilizumab, rituximab, anakinra or tofacitinib) and included CDAI, 28-Joint Modified Disease Activity Score, patient-reported outcomes (including the Health Assessment Questionnaire Disability Index, EuroQol-5 Dimension score, sleep, anxiety, morning stiffness and fatigue) and rates of anaemia. Groups were propensity score-matched at baseline to account for potential confounding.ResultsThere were no statistically significant differences observed between the TNFi and non-TNFi treatment groups for outcomes assessed, except the incidence rate ratio for anaemia, which slightly favoured the TNFi group (19.04 per 100 person-years) versus the non-TNFi group (24.01 per 100 person-years, p=0.03). No potential effect modifiers were found to be statistically significant.ConclusionsThe findings of no significant differences in outcomes between first-line TNF versus first-line non-TNF groups support RA guidelines, which recommend individualised care based on clinical judgement and consideration of patient preferences.

Poliovirus and non-polio-enterovirus environmental surveillance in Parma within the “Global Polio Eradication Program” (GPEI) Background: Environmental surveillance of poliovirus plays an essential role in GPEI both for the detection of WTP and VDPV circulation in endemic areas and for monitoring their absence in polio-free countries. Methods: Since 2005 to 2018, in Parma, 642 wastewater samples were collected from the two wastewater treatment plants and analyzed according to the WHO Guidelines. All isolates supposed being poliovirus were sent to ISS reference laboratory for molecular characterization while NPEV only refer to samples up to 2016. Results: Positivity was obtained in 68% of samples without significant difference between the two treatment plants. Six polioviruses (1.4%) were detected, all characterized as Sabin-like: 4 of them (66.7%) were type 3 and 2 (33.3%) type 1. Coxsackieviruses B mainly recurred among NPEV (85%) while residual 15% was Echoviruses. B4 was the most frequent Coxsackie serotype isolated (31%) while, among Echovirus, Echo 7 and Echo 11 prevail (both 23%). Conclusion: As OPV isn’t used in Italy since 2002, recovery of Sabin-like polioviruses indicates the possibility of poliovirus reintroduction, considering also the important exposure to migratory flows. Finally, monitoring the environmental circulation of NPEV, could compensate for the lack of a surveillance system of the infections they cause. (www.actabiomedica.it)

Objectives A seroprevalence study of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was conducted in a high-incidence area located in northeastern Italy. Methods All citizens above 10 years of age resident in five municipalities of the Autonomous Province of Trento, with the highest incidence of coronavirus disease 2019 (COVID-19) cases, were invited to participate in the study. Among 6098 participants, 6075 sera and a standardized questionnaire administered face-to-face were collected between 5 May and 15 May 2020 and examined. Symptomatic individuals and their family contacts were tested by RT-PCR. Anti-SARS-CoV-2 antibodies were detected using an Abbott SARS-CoV-2 IgG assay, which was performed on the Abbott Architect i2000SR automated analyser. Seroprevalence was calculated as the proportion of positive results among the total number tested. A multivariable logistic regression model was performed to assess the relationship between seropositive versus seronegative individuals for a set of explanatory variables. Results A total of 1402 participants were positive for IgG antibodies against SARS-CoV-2, with a prevalence of 23.1% (1402/6075). The highest prevalence was found in the age class 40–49 years. Overall, 34.4% (2096/6098) of the participants reported at least one symptom. The ratio between reported cases identified by molecular test and those with seropositive results was 1:3, with a maximum ratio of about 1:7 in the age group 70 years old. The infection fatality rate was 2.5% (35/1402). Among the symptoms, anosmia and ageusia were strongly associated with seropositivity. Conclusions The estimated seroprevalence of 23% was three-fold higher than the number of cases reported in the COVID-19 Integrated Surveillance data in the study area. This may be explained in part by a relatively high number of individuals presenting mild or no illness, especially those of younger age, and people who did not seek medical care or testing, but who may contribute to virus transmission in the community.

Anatomical substrate and mechanical trigger co-act in arrhythmia’s onset in patients with bileaflet mitral valve prolapse (bMVP). Feature tracking (FT) may improve risk stratification provided by cardiac magnetic resonance (CMR). The aim was to investigate differences in CMR and FT parameters in bMVP patients with and without complex arrhythmias (cVA and no-cVA). In this retrospective study, 52 patients with bMVP underwent 1.5 T CMR and were classified either as no-cVA (n = 32; 12 males; 49.6 ± 17.4 years) or cVA (n = 20; 3 males; 44.7 ± 11.2 years), the latter group including 6 patients (1 male; 45.7 ± 12.7 years) with sustained ventricular tachycardia or ventricular fibrillation (SVT-FV). Twenty-four healthy volunteers (11 males, 36.2 ± 12.5 years) served as control. Curling, prolapse distance, mitral annulus disjunction (MAD), and late gadolinium enhancement (LGE) were recorded and CMR-FT analysis performed. Statistical analysis included non-parametric tests and binary logistic regression. LGE and MAD distance were associated with cVA with an odds ratio (OR) of 8.51 for LGE (95% CI 1.76, 41.28; p = 0.008) and of 1.25 for MAD (95% CI 1.02, 1.54; p = 0.03). GLS 2D (− 11.65 ± 6.58 vs − 16.55 ± 5.09 1/s; p = 0.04), PSSR longitudinal 2D (0.04 ± 1.62 1/s vs − 1.06 ± 0.35 1/s; p = 0.0001), and PSSR radial 3D (3.95 ± 1.97 1/s vs 2.64 ± 1.03 1/s; p = 0.0001) were different for SVT-VF versus the others. PDSR circumferential 2D (1.10 ± 0.54 vs. 0.84 ± 0.34 1/s; p = 0.04) and 3D (0.94 ± 0.42 vs. 0.69 ± 0.17 1/s; p = 0.04) differed between patients with and without papillary muscle LGE. CMR-FT allowed identifying subtle myocardial deformation abnormalities in bMVP patients at risk of SVT-VF. LGE and MAD distance were associated with cVA. • CMR-FT allows identifying several subtle myocardial deformation abnormalities in bMVP patients, especially those involving the papillary muscle. • CMR-FT allows identifying subtle myocardial deformation abnormalities in bMVP patients at risk of SVT and VF. • In patients with bMVP, the stronger predictor of cVA is LGE (OR = 8.51; 95% CI 1.76, 41.28; p = 0.008), followed by MAD distance (OR = 1.25; 95% CI 1.02, 1.54; p = 0.03).

Background On 11 March 2020, the World Health Organisation (WHO) declared the coronavirus disease 2019 (COVID-19) outbreak to be a pandemic. As the mosquito season progressed, the understandable concern that mosquitoes could transmit the virus began to increase among the general public and public health organisations. We have investigated the vector competence of Culex pipiens and Aedes albopictus, the two most common species of vector mosquitoes in Europe, for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to the very unusual feeding behaviour of Ae. albopictus, we also evaluated the role of this mosquito in a potential mechanical transmission of the virus. Methods For the vector competence study, mosquitoes were allowed to take several infectious blood meals. The mosquitoes were then collected and analysed at 0, 3, 7 and 10 days post-feeding. For the mechanical transmission test, Ae. albopictus females were allowed to feed for a short time on a feeder containing infectious blood and then on a feeder containing virus-free blood. Both mosquitoes and blood were tested for viral presence. Results Culex pipiens and Ae. albopictus were found not be competent vectors for SARS-CoV-2, and Ae. albopictus was unable to mechanically transmit the virus. Conclusions This is the first study to show that the most common species of vector mosquitoes in Europe do not transmit SARS-CoV-2 and that Ae. albopictus is unable to mechanically transmit the virus from a positive host to a healthy host through host-feeding. Graphical Abstract

SummaryBackgroundThere are conflicting results about the duration of antibodies induced by SARS-CoV-2, but several studies show a rapid decay in a few months after infection. To evaluate antibody decline, we re-evaluated the presence of anti-SARS-CoV-2 antibodies among individuals found seropositive in a first population survey conducted 4 months before.MethodsAll individuals above ten years of age resident in 5 municipalities of the Autonomous Province of Trento, northern Italy, who resulted IgG positive for anti-SARS-CoV-2 nucleocapsid (NC) antibodies in a serosurvey conducted on May 2020 were retested after 4 months. Anti-SARS-CoV-2 antibodies were detected using the Abbott SARS-CoV-2 IgG assay (Abbott Diagnostics, USA) detecting anti-NC antibodies. Samples that gave a negative result were re-tested using the same test plus Liaison SARS-CoV-2 IgG assay (DiaSorin, Italy) to assess anti-spike (S) S1/S2 IgG antibodies. Seroprevalence was calculated as the proportion of positive people on the total number of tested. A neutralizing assay was performed on a subgroup of formerly positives sera using fifty-percent tissue culture infective dose (TCID50) as endpoint dilution to produce a cytopathic effect in 50% of inoculated Vero E6 cells culture. In all the analyses a p value < 0.05 were considered statistically significant. Statistical analysis was performed by STATA version 16.1 (STATA Corp., College Station, Texas, USA).FindingsOverall, 1159 out of 1402 initially anti-NC seropositive participants were enrolled in the study. Of them, 480 (41.1%) became seronegative for anti-NC IgG antibodies. When 479 negative sera were tested for anti-S IgG, 373 samples (77.9%) resulted positives. A functional neutralization assay was performed on 106 sera showing high concordance with anti-S antibodies positivity.InterpretationA decline of anti-NC IgG values was recorded 4 months after the first evaluation. Worth of note, a high proportion of anti-NC seronegative individuals were positive for anti-spike IgG antibodies, which appear to persist longer and to better correlate with neutralization activity.

We thank Zheng et al 1 for their interest in our study2 and for providing constructive comments. They mention that even though the baseline mean Clinical Disease Activity Index (CDAI) was not statistically different, the proportion of patients with moderate or high disease at baseline was different and this could have been a key effect modifier.1 We used standardised differences to evaluate variables at baseline. Calculation of the standardised difference not only accounts for the means of the two cohorts, but also the SD. We noticed that continuous CDAI was balanced across the two therapy classes (as listed in the manuscript table 1, SD=−0.015)2 and similarly observed for categorical CDAI (low/moderate/high; SD=0.0515; results not shown …

Whole genome sequences of SARS-CoV-2 obtained from two patients, a Chinese tourist visiting Rome and an Italian, were compared with sequences from Europe and elsewhere. In a phylogenetic tree, the Italian patient’s sequence clustered with sequences from Germany while the tourist’s sequence clustered with other European sequences. Some additional European sequences in the tree segregated outside the two clusters containing the patients’ sequences. This suggests multiple SARS-CoV-2 introductions in Europe or virus evolution during circulation.

Background In RA patients, unacceptable pain (UP) may persist despite inflammation control (refractory pain [RP]). Sarilumab is indicated (either with methotrexate or as monotherapy if methotrexate is not tolerated/appropriate) for adults with moderately-to-severely active RA with an inadequate response or intolerance to ≥ 1 conventional synthetic disease-modifying antirheumatics (csDMARD). The recommended dose is 200 mg every 2 weeks (q2w) with dose reduction to 150 mg if required for management of laboratory abnormalities. Three randomised controlled trials (RCTs) of subcutaneous sarilumab 150 or 200 mg q2w vs comparators showed meaningful improvements in pain. This analysis assessed UP and RP in these trials. Methods RCTs evaluated sarilumab 150 and 200 mg q2w vs placebo (+csDMARDs: MOBILITY/NCT01061736 and TARGET/NCT01709578) and sarilumab 200 mg q2w vs adalimumab 40 mg q2w (MONARCH/NCT02332590). Post-hoc analyses calculated odds ratios (ORs) of UP (based on patient acceptable symptom state on a threshold of visual analog scale pain >40 mm [0-100]), RP (UP+C-reactive protein Results Across all three trials, sarilumab 150 and 200 mg q2w had lower odds of UP (p < 0.05; ORs 0.39-0.46 vs placebo and 0.54 vs adalimumab). In MOBILITY, sarilumab 150 and 200 mg q2w had lower odds (p < 0.05) of RP vs placebo at Week 24 (ORs 0.60 [0.38,0.93] and 0.57 [0.37,0.87]) and Week 52 (ORs 0.64 [0.37,1.02] and 0.62 [0.37,1.02]), and RP-strict at Week 52 (0.41 [0.19,0.90] and 0.35 [0.16,0.76]). In TARGET, sarilumab 150 mg q2w had lower odds (p < 0.05) of RP-strict at Week 24. Higher pain was associated with worse FACIT-fatigue, HAQ, SJC and TJC scores (all p < 0.001). Conclusion Sarilumab was associated with lower odds of UP or RP vs adalimumab or placebo. Disclosures V. Bykerk: Consultancies; Abbvie, Amgen, Brainstorm Therapeutics, Bristol-Myers Squibb, Genentech, Gilead, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi, Scipher, Union Chimique Belge. Shareholder/stock ownership; Abbvie, Amgen, Brainstorm Therapeutics, Bristol-Myers Squibb, Genentech, Gilead, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi, Scipher, Union Chimique Belge. Grants/research support; AbbVie, Amgen, Brainstorm Therapeutics, Bristol-Myers Squibb, Genentech, Gilead, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi, Scipher, Union Chimique Belge. W. Wei: Shareholder/stock ownership; Regeneron Pharmaceuticals, Inc. Other; Regeneron Pharmaceuticals, Inc. S. Boklage: Shareholder/stock ownership; Regeneron Pharmaceuticals, Inc. Other; Regeneron Pharmaceuticals, Inc. T. Kimura: Shareholder/stock ownership; Regeneron Pharmaceuticals, Inc. Other; Regeneron Pharmaceuticals, Inc. S. Fiore: Shareholder/stock ownership; Sanofi. Other; Sanofi. G. St John: Shareholder/stock ownership; Regeneron Pharmaceuticals, Inc. Other; Regeneron Pharmaceuticals, Inc.

Within the initiatives for poliomyelitis eradication by WHO, Italy activated an environmental surveillance (ES) in 2005. ES complements clinical Acute Flaccid Paralysis (AFP) surveillance for possible polio cases, detects poliovirus circulation in environmental sewage, and is used to monitor transmission in communities. In addition to polioviruses, the analyses comprised: (i) the monitoring of the presence of non-polio enteroviruses in sewage samples and (ii) the temporal and geographical distribution of the detected viruses. From 2009 to 2015, 2880 sewage samples were collected from eight cities participating in the surveillance. Overall, 1479 samples resulted positive for enteroviruses. No wild-type polioviruses were found, although four Sabin-like polioviruses were detected. The low degree of mutation found in the genomes of these four isolates suggests that these viruses have had a limited circulation in the population. All non-polio enteroviruses belonged to species B and the most frequent serotype was CV-B5, followed by CV-B4, E-11, E-6, E-7, CV-B3, and CV-B2. Variations in the frequency of different serotypes were also observed in different seasons and/or Italian areas. Environmental surveillance in Italy, as part of the 'WHO global polio eradication program', is a powerful tool to augment the polio surveillance and to investigate the silent circulation or the re-emergence of enteroviruses in the population.

Background: Data-driven principal component (PC) and cluster analysis has the potential to identify previously unknown patient subgroups within a rheumatoid arthritis (RA) registry to establish prognosis, predict disease trajectory, and help inform treatment. Objectives: The Brigham and Women’s Rheumatoid Arthritis Sequential Study (BRASS), established in 2003, is a single-center, prospective observational registry cohort providing a comprehensive set of clinical disease activity measures in >1400 patients with RA. Our objective was to use PC and cluster analysis of baseline demographic, socio-economic, health and disease characteristics in BRASS to identify and characterize distinct patient clusters in RA. Methods: Patient variables recorded at entry into BRASS were refined and combined using PC analysis to reduce dimensionality and collinearity. The number of PCs was established by eigenvalue >1, cumulative variance, and interpretability. Patients were clustered using a k-means approach with non-hierarchical, exclusive, and complete clustering, with minimum cluster size 5% of population, and maximum 19 clusters. The final number of clusters was determined according to the cubic clustering criterion and pseudo F. Results: Analysis of baseline data from 1443 patients identified 41 PCs that capture the fundamental characteristics involved in RA. Cluster analysis distinguished 5 patient clusters. Each cluster reflected a different profile of PCs, and can be described based on overall health, RA disease activity and duration (Table). Key differentiators between clusters include comorbidity PCs (metabolic comorbidities predominate in cluster 1, neurologic in cluster 4, and orthopedic in cluster 5) and patient characteristics/social PCs (greatest number of doctor visits and family history of MI in cluster 3, greatest BMI in cluster 1, highest income in cluster 2, lowest income in cluster 5, and least emotional support in cluster 1). Conclusion: Data-driven cluster analysis of RA patient characteristics at entry into the BRASS registry identified five distinct patient phenotypes, providing a convenient method to potentially derive novel insights into the multifactorial drivers, commonly co-occurring health conditions, and manifestations of RA. Investigation of longitudinal outcomes in these different clusters in the BRASS registry and validation in an independent dataset is ongoing. Acknowledgement: Study funding and medical writing support (Matt Lewis, Adelphi) provided by Sanofi and Regeneron Pharmaceuticals, Inc. Disclosure of Interests: Jeffrey R. Curtis Grant/research support from: Abbvie, Amgen, BMS, Corrona, Janssen, Lilly, Myriad, Pfizer, Roche/Genentech, UCB, Crescendo Bioscience Inc., Consultant for: Abbvie, Amgen, BMS, Corrona, Janssen, Lilly, Myriad, Pfizer, Roche/Genentech, UCB, Crescendo Bioscience Inc., Michael E. Weinblatt Shareholder of: Stock option: CanFite, Lycera, Scipher, Inmedix, Grant/research support from: Crescendo Bioscience, Bristol Myers Squibb, Sanofi, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, CanFite, Corrona, Crescendo, GlaxoSmithKline, Gilead, Horizon, Lilly, Lycera, Merck, Novartis, Pfizer, Roche, Samsung, Scipher, Set Point, Kenneth Saag Grant/research support from: Amgen, Ironwood/AstraZeneca, Horizon, SOBI, Takeda, Consultant for: Abbvie, Amgen, Ironwood/AstraZeneca, Bayer, Gilead, Horizon, Kowa, Radius, Roche/Genentech, SOBI, Takeda, Teijin, Vivian Bykerk Grant/research support from: Mallinckrodt, BMS, Crescendo Biosciences, Sanofi/Regeneron., Consultant for: Amgen, Pfizer, UCB, Scipher, Sanofi/Genzyme/Regeneron, Christina Charles-Schoeman Grant/research support from: Bristol-Myers Squibb, AbbVie, and Pfizer, Consultant for: Regeneron-Sanofi, Pfizer, and Gilead, Stefano Fiore Shareholder of: Sanofi, Employee of: Sanofi, Gregory St. John Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, Toshio Kimura Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., Shen Zheng Consultant for: Sanofi, Clifton Bingham Grant/research support from: BMS, Consultant for: AbbVie, BMS, Eli Lilly, Genentech/Roche, Janssen, Pfizer, Sanofi/Regeneron, Grace Wright Consultant for: Abbvie, Amgen, BMS, Exagen, LILLY, Myriad Autoimmune, NOVARTIS, Pfizer, Sanofi Genzyme Regeneron, UCB, Speakers bureau: Abbvie, Amgen, BMS, Exagen, LILLY, Myriad Autoimmune, NOVARTIS, Sanofi Genzyme Regeneron, UCB, Martin Bergman Shareholder of: Johnson and Johnson (parent company of Janssen), Consultant for: AbbVie, Amgen, BMS, Celgene, Genentech/Roche, Janssen, Merck, Novartis, Pfizer, and Sanofi/Regeneron, Speakers bureau: AbbVie, Amgen, BMS, Celgene, Genentech/Roche, Janssen, Merck, Novartis, Pfizer, and Sanofi/Regeneron, Kamala Nola Shareholder of: Gilead, Johnson & Johnson, Proctor & Gamble, Consultant for: Yes – Gilead, Sanofi Genzyme, Regeneron, Speakers bureau: Coherus, Daniel E. Furst Grant/research support from: AbbVie, Actelion, Amgen, BMS Corbus, NIH, Novartis, Pfizer, Roche/Genentech, Consultant for: AbbVie, Actelion, Amgen, BMS, Cytori, Novartis, Pfizer, Roche/Genentech, Speakers bureau: CMC Connect (McCann Health Company), Nancy Shadick Grant/research support from: Mallinckrodt, BMS, Crescendo Biosciences, Sanofi/Regeneron.

Background:Guidelines recommend adjusting therapy in patients with rheumatoid arthritis (RA) who fail to reach and sustain low disease activity (LDA) or remission (disease control). Many factors can affect the decision to change therapy, including the potential for improvement as well as the fear of potential worsening or loss of improvement already achieved. Although data exist on response to treatment in patients who switch therapy, data addressing the likelihood of worsening are limited.Objectives:The aim of this analysis was to describe the demographic, clinical characteristics, and change in clinical outcomes in patients on biologic/targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) who had some improvement in clinical disease activity index (CDAI) but did not achieve LDA after ~ 6-12 months of treatment and then switched to a different b/tsDMARD.Methods:This study included adult inadequately responding RA patients from the CORRONA registry who: (1) started a biologic or Janus kinase inhibitor (JAKi) between January 2010 to November 2020 (V1), (2) had any CDAI improvement (i.e., decrease ≥1 unit) but were not in LDA or remission at a subsequent visit (baseline [BL]) occurring 3 to 15 months after V1; (3) had a third visit (follow-up [F/U]) 6 (±3) months after BL with a valid CDAI measure; (4) switched therapy at the BL or between BL and F/U, with the switch occurring at least 3 months prior to the F/U. CDAI >10 and ≤22 was defined as moderate disease activity (MDA) and CDAI >22 was defined as high disease activity (HDA). Two thresholds of change in CDAI (≥6 and ≥12 units) were used to define meaningful improvement and meaningful worsening after the switch. If there was no meaningful improvement or meaningful worsening, this was considered as no meaningful change (-5 to +5 for 6 units change and -11 to +11 for 12 units change). These thresholds for meaningful change were set for all switchers regardless of their pre-switch CDAI value. Descriptive statistics were generated for demographic and clinical characteristics for the switchers at BL, and the change of clinical outcomes was evaluated from BL to F/U.Results:Of the 1,224 patients fulfilling the inclusion criteria, 93 (7.6%) switched therapy and 1,131 (92.4%) did not switch therampy after not achieving an adequate response on the initial b/tsDMARD. At BL, 42.5% and 70.0% of patients had no meaningful improvement to their prior therapy based on ≥6 and ≥12-unit change, respectively; mean (SD) age was 53.1 (14.0) years; duration of RA 10.7 (10.4) years; CDAI 22.2 (10.8); 81.7% were female; 64.5% had MDA, 35.5% had HDA; 21.5 % reported being disabled, 24.7% were current smokers, and 50% were obese. In terms of prior biologic use 57.0%, 22.6%, and 20.4% had been on 1, 2, and 3+, respectively. From BL to F/U, meaningful worsening occurred in 30.1% and 12.9% using a threshold of 6 and 12, respectively, with the remaining patients experiencing meaningful improvement or no meaningful change (Figure 1).Figure 1.Meaningful Worsening, Meaningful Improvement, and No Meaningful Change Based on CDAI Change Thresholds of ≥6 and ≥12 From BL to F/U (N=93)Conclusion:In our analysis, a large proportion of patients who initiated a biologic/JAKi and experienced some improvement but failed to attain LDA or remission, did not switch therapy within approximately a year. This analysis consisted of many patients who did not have a meaningful response to their prior biologic/JAKi, patients who had received multiple prior biologics, and a large portion of patients with poor prognostic factors. Despite this, the proportion of patients with meaningful worsening was low compared with most patients who had either meaningful improvement or no meaningful change. Additional research is warranted to understand the reasons for not switching and whether the likelihood of a meaningful change correlates with prior response, poor prognosis, or other factors.Acknowledgements:Amy Praestgaard (Sanofi) contributed to the statistical analysis for this abstract. Medical writing support for this abstract was provided by Krishna Kammari (Sanofi).Disclosure of Interests:Jeffrey Curtis Grant/research support from: and personal fees from AbbVie, Amgen, BMS, CORRONA, Eli Lily, Janssen, Myriad, Pfizer, Roche, Regeneron, Radius, UCB, outside the submitted work, Stefano Fiore Shareholder of: Sanofi, Employee of: Sanofi. In addition, he has a patent EP 19306553.9; USPTO #s 62/799,698; 62/851,474; 62/935,395 issued, Kerri Ford Shareholder of: Sanofi, Employee of: Sanofi, Judson Janak: None declared, Hong Chang: None declared, Dimitrios A Pappas Employee of: CORRONA LLC. He has previously acted as a consultant for Sanofi, Abbvie, Gtech Roche Hellas, and Novartis. He has an equity interest in CORRONA LLC. and is on the Board of directors of the CORRONA research foundation, Taylor Blachley: None declared, Kelechi Emeanuru: None declared, Vivian Bykerk Grant/research support from: reports grants from Amgen, BMS, UCB, and Novartis were given to institution, that grants from the NIH, PCORI, and CIHR were given to institutions which whom she is affiliated, and that she has received personal fees from Amgen, Gilead, BMS, Pfizer, Sanofi Aventis, Roche, UCB and Regeneron, outside the submitted work.

Background:Rheumatoid arthritis (RA) patients who fail therapy may be switched to any of the five classes of biological disease-modifying antirheumatic drugs (DMARDs) and targeted synthetic DMARDs, to meet treatment goals. Physicians may hesitate to switch between Janus Kinase inhibitors (JAKi) and interleukin-6 receptor inhibitors (IL-6Ri) since they both impact IL-6 signalling and due to limited data on switching between the two classes.Objectives:This retrospective, observational study based on the real-world Corrona RA registry aimed to describe the response in RA patients switching between IL-6Ri and JAKi.Methods:Adult RA patients who initiated either IL-6Ri or JAKi after November 2012 and had a six-month post-initiation follow-up visit were eligible. Patients in ‘Cohort A’ initiated an IL-6Ri following discontinuation of a JAKi and those in ‘Cohort B’ initiated a JAKi following discontinuation of an IL-6Ri. Disease activity measures and patient-reported outcomes (PROs) were evaluated at baseline and at six-month follow-up. Within each group, change from baseline was assessed for Clinical Disease Activity Index (CDAI), Health Assessment Questionnaire (HAQ), pain, fatigue, tender joint count (TJC), swollen joint count (SJC), physician global assessment (MDGA), patient global assessment (PtGA) and morning stiffness duration. Proportion of patients achieving CDAI low disease activity (LDA), CDAI remission and minimal clinically important difference (MCID) for HAQ, pain, fatigue, MDGA, PtGA were assessed. Adjusted linear and logistic regression models were performed for between-group comparisons (Cohort A vs Cohort B) excluding initiators who switched therapy prior to six-month visit.Results:Cohorts A and B included 122 and 144 initiators, respectively. Patients who switched toIL-6Ri (vs JAKi) were younger (mean [SD] age, 56.2 [11.3] vs 58.9 [12.6] years), had higher baseline CDAI (23.2 [12.9] vs 20.2 [12.8]), had higher prior use of ≥2 csDMARDs (75% vs 65%), and were less likely to initiate therapy as monotherapy (44% vs 50%).In Cohort A, significant changes from baseline were observed for all continuous outcomes except HAQ and fatigue. In Cohort B, a significant improvement was observed only for patient-reported pain (Table 1).Table 1.Unadjusted Within-Group Change from Baseline to Six Months, Mean (95% CI), nOutcomesCohort A, N = 122Cohort B, N = 144CDAI-4.7 (-7.6, -1.9), 109-2.4 (-5.2, 0.4), 116HAQ-0.0 (-0.1, 0.1), 105-0.1 (-0.1, 0.0), 118Patient-reported pain-8.2 (-13.4, -3.0), 109-5.9 (-11.5, -0.2), 120Patient-reported fatigue-4.4 (-9.0, 0.2), 109-1.7 (-6.6, 3.3), 117TJC-1.6 (-3.0, -0.1), 112-1.2 (-2.6, 0.3), 117SJC-1.5 (-2.5, -0.4), 112-0.4 (-1.3, 0.6),117MDGA-10.9 (-15.6, -6.3), 112-4.3 (-8.7, 0.2), 117PtGA-6.0 (-11.2, -0.8), 109-4.8 (-10.5, 0.8), 120Morning stiffness durationa-1.3 (-2.2, -0.5), 109-0.1 (-1.1, 0.8), 118aAmong those reporting morning stiffness at baseline.In the adjusted between-group comparison (data not shown) of change from baseline, there were no significant differences in clinical outcomes between Cohorts A and B.In both cohorts, patients achieved CDAI LDA, CDAI remission, and MCIDs across other PROs (Figure 1). In the adjusted between-group comparison (data not shown), the results were similar with the exception of achievement of CDAI LDA among patients with moderate to high disease activity at baseline.Figure 1.Rates of CDAI LDA, CDAI Remission, and MCID for PROsa at Six MonthsConclusion:In general, in both cohorts a substantial proportion of patients achieved CDAI LDA and MCID across PROs. Despite some overlap of JAKi and IL-6Ri therapies’ on the IL-6 pathway, there are some distinct mechanisms of action which may result in meaningful improvements for a subset of patients.Acknowledgements:Amy Praestgaard (Sanofi) contributed to the interpretation of the statistical analysis for this abstract. Medical writing support for this abstract was provided by Nupur Chaubey (Sanofi).Disclosure of Interests:Anisha Dua Speakers bureau: AbbVie, Consultant of: Consulting/advisory board for AbbVie, Novartis, and Chemocentryx, Employee of: Board member of Vasculitis foundation and Chicago Rheumatism Society, Kerri Ford Shareholder of: Sanofi, Employee of: Sanofi, Stefano Fiore Shareholder of: Sanofi, Employee of: Sanofi. In addition, Stefano Fiore has a patent EP 19306553.9; USPTO #s 62/799,698; 62/851,474; 62/935,395 issued, Dimitrios A Pappas Shareholder of: Corrona LLC, Consultant of: Sanofi, AbbVie, Gtech, Roche Hellas, and Novartis, Employee of: Corrona LLC. Board of directors, Corrona Research Foundation, Judson Janak: None declared, Taylor Blachley: None declared, Carla Roberts-Toler: None declared, Kelechi Emeanuru: None declared, Joel Kremer Consultant of: AbbVie, Lilly, Novartis, Pfizer, BMS, Genentech, Regeneron, Sanofi, and Corrona, Grant/research support from: AbbVie, Lilly, Novartis, and Pfizer, Alan Kivitz Shareholder of: Pfizer, Sanofi, GlaxoSmithKline, Gilead Sciences, Inc., and Novartis, Speakers bureau: Celgene, Merck, Lilly, Novartis, Pfizer, Sanofi, Flexion, and AbbVie, Consultant of: AbbVie, Boehringer Ingelheim, Flexion, Janssen, Pfizer, Sanofi, Regeneron, SUN Pharma Advanced Research, Gilead Sciences, Inc. In addition, Alan Kivitz reports other from Altoona Center for Clinical Research, PC, during the conduct of the study.

Background:Patients with rheumatoid arthritis (RA) who have received multiple biologics or targeted therapies over time tend to have more refractory and more severe disease, which may lead to worse clinical response to treatment.Objectives:We used data from the ACR RISE registry to assess whether disease severity was greater in those who received sarilumab shortly after its FDA approval (May 2017) than in subsequent time periods and to evaluate the effectiveness of sarilumab in populations with various degrees of disease severity.Methods:Patients with RA who initiated sarilumab treatment in the period 2017-2020 were identified in the ACR RISE registry and divided into Cohort 1 (2017, year of the FDA approval) and the calendar year-based Cohorts 2-4 (2018-2020). Patient demographics, RA-related features, and comorbidities were determined using data prior to sarilumab initiation. The cohorts were compared using chi-square test (categorical variables) and a nonparametric test (continuous variables). Sarilumab effectiveness was assessed using 3 cohorts assembled based on progressively restrictive criteria: Active Disease cohort (Clinical Disease Activity Index [CDAI] >10 or Routine Assessment of Patient Index Data 3 [RAPID3] >6, and C-reactive protein, if measured, ≥8 mg/L), TARGET Eligibility cohort (patients who satisfied enrolment criteria for TARGET,1 a Phase 3 sarilumab trial in patients with RA and an inadequate response to TNF inhibitors), and TARGET Baseline cohort (patients from TARGET Eligibility cohort with characteristics weighted to match those from the TARGET trial baseline,1 using the matching-adjusted indirect comparison method2). In all 3 effectiveness cohorts, mean changes in CDAI and RAPID3 at 6 and 12 months post-initiation of sarilumab were evaluated using a model adjusted for baseline score, age, sex, race, calendar year, and seropositivity.Results:A total of 2949 patients, treated by 585 rheumatologists, initiated sarilumab treatment in the period 2017–2020. The 4 yearly cohorts were relatively similar in terms of patients’ age, sex, race, and most clinical characteristics. However, patients receiving sarilumab shortly after FDA approval (Cohort 1) had more ambulatory visits, a greater number of previously used non-TNFi biologics (particularly tocilizumab), and a higher comorbidity burden, and were more likely to be current users of glucocorticoids or opioids than sarilumab initiators in the subsequent 3 years. In the 3 cohorts used to assess sarilumab effectiveness, the greatest improvement was observed in the TARGET Baseline cohort, which also had the greatest mean baseline CDAI score (43), compared with the other two (24 both).Conclusion:In this real-world cohort, we observed modest evidence for channeling of patients with greater RA severity and greater prior exposure to non-TNFi biologics to sarilumab shortly after its FDA approval. This cohort effect did not diminish the effectiveness of sarilumab. All cohorts showed improvement, with the greatest clinical improvement observed in the cohort with the highest baseline CDAI score who most closely resembled those enrolled in a phase 3 trial of patients with an inadequate response to TNF inhibitors.References:[1]Fleischmann R, et al. Arthritis Rheumatol 2017;69:277-290.[2]Signorovitch JE et al. Value Health 2012;15:940-7.Figure 1.Adjusted improvements in CDAI and RAPID3Acknowledgements:This study was sponsored by Sanofi. Medical writing support was provided by Vojislav Pejović, PhD (Eloquent Medical Affairs, division of Envision Pharma Group) and funded by Sanofi.Disclosure of Interests:Stefano Fiore Employee of: Sanofi, Lang Chen: None declared, Cassie Clinton Consultant of: Information available in profile, Huifeng Yun Grant/research support from: Research support for Pfizer, Amy Praestgaard Employee of: Sanofi, Kerri Ford Employee of: Sanofi, Jeffrey Curtis Consultant of: Received consulting and research grants from AbbVie, Amgen, BMS, Lilly, Gilead, GSK, Janssen, Myriad, Pfizer, Roche, Samsung, Sandoz, Sanofi, UCB, Grant/research support from: Received consulting and research grants from AbbVie, Amgen, BMS, Lilly, Gilead, GSK, Janssen, Myriad, Pfizer, Roche, Samsung, Sandoz, Sanofi, UCB

Background Enterovirus infections can cause a variety of illnesses, ranging from asymptomatic infections to severe illness and death. Aim To support polio eradication activities, in February 2019, the WHO Regional Reference Laboratory for polio in Italy, at the National Institute of Public Health (Istituto Superiore di Sanita), promoted an investigation on non-polio enterovirus laboratory capacity, with the support of the Italian Ministry of Health. The aim was to collect data on the assays used routinely for diagnostic purposes and to characterize enterovirus outbreaks strains by sequence analysis of the Viral Protein 1 region. Methods A questionnaire was administered to public health laboratories through all Italian Regions for 2018 and subsequently, an electronic form for lab-confirmed enterovirus infection reported from February 2019 to January 2020, including patients clinical characteristics, and laboratory data was distributed through 25 laboratories participating the survey. Results Overall, a homogenous laboratory capacity for enterovirus infection diagnosis was found and 21,000 diagnostic tests were retrospectively reported in 2018. Then, in 2019, two outbreaks of Echovirus 30 were identified and confirmed by molecular analyses. Conclusion These results underline the need monitor the circulation of non-polio enterovirus to ascertain the real burden of the disease in the country.

Background:Anemia is a common comorbidity in patients with rheumatoid arthritis (RA).Objectives:Assess whether low hemoglobin (Hb) identifies a subgroup of patients at increased risk of joint damage progression, and investigate whether sarilumab modulates this risk.Methods:The 52-week, double-blind, Phase 3 MOBILITY trial (NCT01061736) in patients with active RA and inadequate response to methotrexate (n = 1197) demonstrated the tolerability and efficacy (clinical and radiographic) of subcutaneous sarilumab 150 and 200 mg every 2 weeks versus placebo, both in combination with methotrexate (MTX). In thispost hocanalysis, baseline characteristics and radiographic outcomes in MOBILITY were analyzed by baseline Hb category (low or normal) according to World Health Organization criteria, with low Hb defined as Pvalues are presented.Results:A total of 414 patients (35%) had low Hb at baseline. Patients with low Hb were more likely than patients with normal Hb to be female (86% vs 79%, respectively), Asian (14% vs 5%), younger (mean age 49 vs 51 years), and to have lower body weight (mean 69 vs 77 kg); all nominalPPTable.Mean change from baseline (SD) in radiographic measures of joint damagePlacebo+ MTXSarilumab 150 mg+ MTXSarilumab 200 mg+ MTXLow Hb (n = 140)Normal Hb (n = 258)Low Hb (n = 145)Normal Hb (n = 255)Low Hb (n = 129)Normal Hb (n = 270)mTSS3.75 (9.00)2.29 (6.98)1.20*** (5.58)0.73** (4.07)0.60*** (4.13)0.08*** (4.83)Joint space narrowing1.52 (3.71)1.22 (3.92)0.79* (3.17)0.30** (2.70)0.50** (2.93)0.06*** (3.33)Erosion score2.24 (6.24)1.07 (3.91)0.41*** (3.18)0.44* (2.05)0.10*** (2.13)0.02*** (2.19)NominalP*Conclusion:Overall, sarilumab slowed joint damage progression in patients with RA. Additionally, in those patients with low Hb, who may suffer greater damage than those with normal Hb, sarilumab also increased Hb.Acknowledgments:Study funding and medical writing support (Matt Lewis, PhD, of Adelphi Communications Ltd, Macclesfield, UK) were provided by Sanofi Genzyme (Cambridge, MA, USA) and Regeneron Pharmaceuticals, Inc. (Tarrytown, NY, USA) in accordance with Good Publication Practice (GPP3) guidelines.Disclosure of Interests:Gerd Rüdiger Burmester Consultant of: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Speakers bureau: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Jean-Pierre Morello Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., Owen Hagino Shareholder of: Sanofi, Employee of: Sanofi, Amy Praestgaard Employee of: Sanofi Genzyme, Stefano Fiore Shareholder of: Sanofi, Employee of: Sanofi, Mark C. Genovese Grant/research support from: Abbvie, Eli Lilly and Company, EMD Merck Serono, Galapagos, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, Pfizer Inc., RPharm, Sanofi Genzyme, Consultant of: Abbvie, Eli Lilly and Company, EMD Merck Serono, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, RPharm, Sanofi Genzyme

Hereby, the partial Viral Protein 1 sequences of Coxsackievirus B5 (CV-B5) from sewage samples, collected in Italy from 2016 to 2017, were compared with those available in GenBank from clinical samples. Phylogenetic analysis highlighted: (I) the predominant circulation of CV-B5 genogroup B in Italy, and (II) the presence of two new sub-genogroups.

Human enteroviruses (HEVs) occur in high concentrations in wastewater and can contaminate receiving environmental waters, constituting a major cause of acute waterborne disease worldwide. In this study, we investigated the relative abundance, occurrence, and seasonal distribution of polio and other enteroviruses at three wastewater treatment plants (WWTPs) in Naples, Southern Italy, from January 2010 to December 2014. Influent and effluent samples from the three WWTPs were collected monthly. One hundred and sixty-one of the 731 wastewater samples collected (22.0%) before and after water treatment were CPE positive on RD cells; while no samples were positive on L20B cells from any WWTPs. Among the 140 non-polio enterovirus isolated from inlet sewage, 69.3% were Coxsackieviruses type B and 30.7% were Echoviruses. Among these, CVB3 and CVB5 were most prevalent, followed by CVB4 and Echo6. The twenty-one samples tested after treatment contained 6 CVB4, 5 CVB3, 3 Echo11, and 2 Echo6; while other serotypes were isolated less frequently. Data on viral detection in treated effluents of WWTPs confirmed the potential environmental contamination by HEVs and could be useful to establish standards for policies on wastewater management.

To analyze with diffusion-weighted magnetic resonance imaging (DW-MRI) the evolution and progress to resolution of acute pyelonephritis (APN) foci over a period of 3 months after onset. 30 women (age 22–51 years) with clinical, laboratory (white blood cell and C-reactive protein), and DW-MRI (4b-values 0, 50, 600, 1000 s/mm2) diagnosis of APN were prospectively enrolled. Two double-blinded radiologists evaluated the number of APN foci, and for each of them dimension (D), absolute diffusion coefficient (ADC), and its ratio R to the ADC of unaffected parenchyma. Signature of radiological recovery was focus no longer visible (DW−) and ADC of its site not inferior to the ADC of the unaffected parenchyma, i.e., R ≥ 0.9. Clinical and DW-MRI follow-ups (FU) were performed at 1 and 3 months. At the acute stage (t 0), 187 APN foci were found, with ADC0 = 1.3 ± 0.2 × 10−3 mm2/s, R 0 = 0.65 ± 0.12, and D 0 = 14 ± 7.5 mm. By the 1-month FU (t 1), all patients had no symptoms and physiological laboratory values; despite this, only 80 (43%) foci were solved, increasing to 138 (74%) by at the 3-month FU. The ROC curve (AUC ≥ 0.80) identified R 0 ≤ 0.6 and D 0 > 15 mm as forecast of slow radiologic resolution. About 80% of foci unsolved at 1 month but with R 1 ≥ 0.8 and D 1 ≤ 10 mm reached solution at 3 months. DW-MRI recovery of APN foci does not always coincide with clinical recovery. The evolution of an APN focus is shaped by its initial values R 0 and D 0. About half of the foci still visible at 1 month reached radiological resolution in the two following months.

Aims Human Enteroviruses (HEVs) infections have a significant impact on public health, being implicated in outbreaks of meningitis, encephalitis, hand-foot-mouth disease and other acute and chronic manifestation. In the strategic plan for poliomyelitis eradication, the environmental surveillance of poliovirus (PV) has been identified by the World Health Organization (WHO) as an activity that can complement the surveillance of polio. Having wastewater samples available for PV surveillance allows us to study nonpolio enteroviruses (NPEVs) circulating in the study population, which are widely spread. Methods and Results This study was carried out according to the WHO guidelines for environmental surveillance of PV and analysed the circulation of PV and NPEVs through the isolation of viruses in cell cultures in Milan area; from 2006 to 2010, 321 wastewater samples were collected, regularly over time, at the inlet of three diverse waste water treatment plants (WWTPs). Culturable HEVs were isolated in 80% of sewage samples: all isolates belonged to the HEV-B group and those circulating more intensely were CVB5 and Echo 6, while CVB4 was the predominant serotype found in 2010. In this study, two type 2 PVs were isolated, both characterized as Sabin like. Conclusion Environmental monitoring of HEVs in Milan has proved to be an interesting tool to investigate the circulation and distribution of viruses. Significance and Impact of the Study The detection of PV and other NPEV could be predictive of possible re-emergence of these viruses with an impact on public health. NPEV monitoring could also be a powerful public health tool to investigate the possible role of NPEV in different clinical manifestations.

The WHO Regional Commission for the Certification of Poliomyelitis Eradication has recently indicated Bosnia and Herzegovina (B&H) as a high risk country for transmission, following importation, of wild poliovirus (WPV) or circulating vaccine-derived poliovirus (cVDPV). We analyzed data on Acute Flaccid Paralysis (AFP) surveillance between 2007 to 2016, and the trend of polio immunization coverage in B&H. The majority of AFP cases was recorded in 2016 suggesting an enhancement of the AFP surveillance activities. However, the decline in the immunization coverage, around 74%, and the isolation of two Sabin-like poliovirus type 2 strains, one of them close to a VDPV, require a particular attention in the area. Although B&H has successfully maintained its polio-free status since 2002 several challenges need to be addressed. This article is protected by copyright. All rights reserved

Although in the last years poliovirus (PV) transmission has been reported at the lowest levels ever recorded, the spread of virus from endemic countries endures; the high levels of immigration flows across the Mediterranean Sea jeopardize Italy for PV reintroduction. The World Health Organization (WHO) strategic plan for global poliomyelitis (polio) eradication indicates the nationwide surveillance of Acute Flaccid Paralysis (AFP) as the gold standard for detecting cases of polio. In addition, the Environmental Surveillance (ES), seeking the presence of PV and Non-Polio Enterovirus (NPEV) in sewage, is recognized as a powerful tool to confirm PV circulation in absence of AFP cases, especially in polio-free countries. Here we report the results of AFP surveillance (AFPS) and ES in Lombardy (Northern Italy) from 2012 to 2015. Forty-eight AFP cases were identified during the study period. No AFP case was caused by PV infection. NPEVs were identified in 6.3% (3/48) of AFP cases. The annual AFP incidence rate was 0.87/100'000 children15 y in 2012, 1.42/100'000 in 2013, 1.02/100'000 in 2014, and 0.47/100'000 in 2015; according to WHO indicators, the sensitivity of AFPS was adequate in 2013 and 2014. Completeness of case investigation raised progressively during the study period to achieve the WHO standards in 2014 (92.3%) and 2015 (100%). Completeness of follow-up increased from 72.7% in 2012 to 100% in 2014. In the framework of the ES conducted in Milan, 268 wastewater samples were collected from 2012 to 2015 and no PVs were isolated. In contrast, NPEVs were detected in 65.3% (175/268) of samples. All NPEVs characterized belonged to enterovirus species B: echovirus type 11, 6 and 3 were the most frequently detected viruses, representing 29.1% (41/141), 20.6% (29/141) and 9.2% (13/141) of genotyped NPEVs, respectively. Keeping strong and encouraging both AFPS and ES is crucial to ensure that PV will not return unnoticed in Italy - as well as in other polio-free countries - and, as a final point, to achieve the global polio eradication goal.

Interleukin 6 (IL-6) signaling plays a key role in the pathophysiology of rheumatoid arthritis (RA) and is inhibited by sarilumab, a human monoclonal antibody blocking the IL-6 receptor alpha (IL-6Rα). The effects of sarilumab plus methotrexate (MTX) on serum biomarkers of joint damage and bone resorption were assessed in two independent studies (phase II (part A) and phase III (part B)) of patients with RA with a history of inadequate response to MTX from the MOBILITY study (NCT01061736). Serum samples were analyzed at baseline and prespecified posttreatment time points. Biomarkers of tissue destruction, cartilage degradation, and synovial inflammation were measured in part A; assessment of these markers was repeated in part B and included additional analysis of biomarkers of bone formation and resorption (including soluble receptor activator of nuclear factor-kB ligand (sRANKL)). A mixed model for repeated measures was used to compare treatment effects on change in biomarkers. Additionally, changes from baseline in biomarkers were compared between American College of Rheumatology 50 % responders and nonresponders and between patients who achieved or did not achieve low disease activity (LDA), separately by treatment group, at week 24. In part A, sarilumab 150 and 200 mg every 2 weeks (q2w) significantly reduced biomarkers of tissue destruction, cartilage degradation, and synovial inflammation at both 2 and 12 weeks posttreatment (p