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

Influenza vaccination for elderly, vulnerable and high-risk subjects: a narrative review and expert opinion

Influenza is associated with a substantial health burden, especially in high-risk subjects such as older adults, frail individuals and those with underlying chronic diseases. In this review, we summarized clinical findings regarding the impact of influenza in vulnerable populations, highlighted the benefits of influenza vaccination in preventing severe illness and complications and reviewed the main evidence on the efficacy, effectiveness and safety of the vaccines that are best suited to older adults among those available in Italy. The adverse outcomes associated with influenza infection in elderly and frail subjects and those with underlying chronic diseases are well documented in the literature, as are the benefits of vaccination (mostly in older adults and in patients with cardiovascular diseases, diabetes and chronic lung disease). High-dose and adjuvanted inactivated influenza vaccines were specifically developed to provide enhanced immune responses in older adults, who generally have low responses mainly due to immunosenescence, comorbidities and frailty. These vaccines have been evaluated in clinical studies and systematic reviews by international immunization advisory boards, including the European Centre for Disease Prevention and Control. The high-dose vaccine is the only licensed influenza vaccine to have demonstrated greater efficacy versus a standard-dose vaccine in preventing laboratory-confirmed influenza in a randomized controlled trial. Despite global recommendations, the vaccination coverage in high-risk populations is still suboptimal. All healthcare professionals (including specialists) have an important role in increasing vaccination rates

Immunogenicity and Safety of Adjuvanted Recombinant Zoster Vaccine in Rheumatoid Arthritis Patients on Anti-Cellular Biologic Agents or JAK Inhibitors: A Prospective Observational Study

Rheumatoid arthritis (RA) patients on JAK inhibitors (JAKi) have an increased HZ risk compared to those on biologic DMARDs (bDMARDs). Recently, the Adjuvanted Recombinant Zoster Vaccine (RZV) became available worldwide, showing good effectiveness in patients with inflammatory arthritis. Nevertheless, direct evidence of the immunogenicity of such a vaccine in those on JAKi or anti-cellular bDMARDs is still lacking. This prospective study aimed to assess RZV immunogenicity and safety in RA patients receiving JAKi or anti-cellular bDMARDs that are known to lead to impaired immune response. Patients with classified RA according to ACR/EULAR 2010 criteria on different JAKi or anti-cellular biologics (namely, abatacept and rituximab) followed at the RA clinic of our tertiary center were prospectively observed. Patients received two shots of the RZV. Treatments were not discontinued. At the first and second shots, and one month after the second shot, from all patients with RA, a sample was collected and RZV immunogenicity was assessed and compared between the treatment groups and healthy controls (HCs) receiving RZV for routine vaccination. We also kept track of disease activity at different follow-up times. Fifty-two consecutive RA patients, 44 females (84.61%), with an average age (±SD) of 57.46 ± 11.64 years and mean disease duration of 80.80 ± 73.06 months, underwent complete RZV vaccination between February and June 2022 at our center. At the time of the second shot (1-month follow-up from baseline), anti-VZV IgG titer increased significantly in both groups with similar magnitude (bDMARDs: 2258.76 ± 897.07 mIU/mL; JAKi: 2059.19 ± 876.62 mIU/mL, p < 0.001 for both from baseline). At one-month follow-up from the second shot, anti-VZV IgG titers remained stable in the bDMARDs group (2347.46 ± 975.47) and increased significantly in the JAKi group (2582.65 ± 821.59 mIU/mL, p = 0.03); still, no difference was observed between groups comparing IgG levels at this follow-up time. No RA flare was recorded. No significant difference was shown among treatment groups and HCs. RZV immunogenicity is not impaired in RA patients on JAKi or anti-cellular bDMARDs. A single shot of RZV can lead to an anti-VZV immune response similar to HCs without discontinuing DMARDs

Long-term safety of rituximab in rheumatic patients with previously resolved hepatitis B virus infection

Conflicting results can be found in the literature on the frequency of hepatitis B virus (HBV) reactivation (HBVr) on rituximab (RTX) in rheumatic patients with previously resolved HBV (prHBV) infection. Here, we report the frequency of HBVr in a large historical cohort of caucasian rheumatic patients with prHBV receiving RTX. Registry data of rheumatic patients treated with RTX were retrospectively analysed. Demographic and clinical characteristics including evaluation of anti-HCV and HBV markers, annual HBV-DNA determination and aminotransferase levels assessed every three months, were recorded. Kaplan–Meier estimate was used to compare the risk of being still under therapy at different time points in patients with or without prHBV infection. Cox regression analysis was used to determine the association between recorded variables and treatment discontinuation. A total of 311 patients treated with RTX, 44 (14.1%) with and 267 (85.9%) without prHBV were analysed. No significant difference between the two groups regarding demographic and clinical characteristics was observed. During RTX treatment, detectable HBV-DNA and reappearance of HBsAg in patients with prHBV (seroreversion) were never observed. Kaplan–Meier functions were similar in patients with or without prHBV infection which was not associated with RTX discontinuation neither at univariate nor at multivariate analysis. These data are in favor of the concept that patients with rheumatologic diseases have a very low risk of reactivation of the HBV infection under RTX treatment. However, future prospective studies, including a larger number of patients, are still necessary to draw definitive conclusions

A nosocomial measles outbreak in Italy, February-April 2017

We describe a nosocomial outbreak of measles that occurred in an Italian hospital during the first months of 2017, involving 35 persons and including healthcare workers, support personnel working in the hospital, visitors and community contacts. Late diagnosis of the first case, support personnel not being promptly recognised as hospital workers and diffusion of the infection in the emergency department had a major role in sustaining this outbreak

Hospital admission and mortality rates for non-Covid diseases among residents of the long-term care facilities before and during the pandemic: a cohort study in two Italian regions

Aim: Long-term-care facility residents are a vulnerable population who experienced reduced healthcare access during the pandemic. This study aimed to assess the indirect impact of the COVID-19 pandemic, in terms of hospitalisation and mortality rates, among this population in two Italian Regions, Tuscany and Apulia, during 2020 in comparison with the pre-pandemic period. Subject and methods: We conducted a retrospective cohort study on people residing in long-term-care facilities from 1 January 2018 to 31 December 2020 (baseline period: 1 January 2018-8 March 2020; pandemic period: and 9 March-31 December 2020). Hospitalisation rates were stratified by sex and major disease groups. Standardised weekly rates were estimated with a Poisson regression model. Only for Tuscany, mortality risk at 30 days after hospitalisation was calculated with the Kaplan-Meier estimator. Mortality risk ratios were calculated using Cox proportional regression models. Results: Nineteen thousand two hundred and fifty individuals spent at least 7 days in a long-term-care facility during the study period. The overall mean non-Covid hospital admission rate per 100 000 residents/week was 144.1 and 116.2 during the baseline and pandemic periods, with a decrease to 99.7 and 77.3 during the first (March-May) and second lockdown (November-December). Hospitalisation rates decreased for all major disease groups. Thirty-day mortality risk ratios for non-Covid conditions increased during the pandemic period (1.2, 1.1 to 1.4) compared with baseline. Conclusion: The pandemic resulted in worse non-COVID-related health outcomes for long-term-care facilities' residents. There is a need to prioritise these facilities in national pandemic preparedness plans and to ensure their full integration in national surveillance systems. Supplementary information: The online version contains supplementary material available at 10.1007/s10389-023-01925-1

Invasive pneumococcal disease in tuscany region, Italy, 2016–2017: Integrating multiple data sources to investigate underreporting

Invasive pneumococcal disease (IPD) is a vaccine-preventable disease characterized by the presence of Streptococcus pneumoniae in normally sterile sites. Since 2007, Italy has implemented an IPD national surveillance system (IPD-NSS). This system suffers from high rates of underreporting. To estimate the level of underreporting of IPD in 2016–2017 in Tuscany (Italy), we integrated data from IPD-NSS and two other regional data sources, i.e., Tuscany regional microbiological surveillance (Microbiological Surveillance and Antibiotic Resistance in Tuscany, SMART) and hospitalization discharge records (HDRs). We collected (1) notifications to IPD-NSS, (2) SMART records positive for S. pneumoniae from normally sterile sites, and (3) hospitalization records with IPD-related International Classification of Diseases, Ninth Revision, Clinical Modification (ICD9) codes in discharge diagnoses. We performed data linkage of the three sources to obtain a combined surveillance system (CSS). Using the CSS, we calculated the completeness of the three sources and performed a three-source log-linear capture–recapture analysis to estimate total IPD underreporting. In total, 127 IPD cases were identified from IPD-NSS, 320 were identified from SMART, and 658 were identified from HDRs. After data linkage, a total of 904 unique cases were detected. The average yearly CSS notification rate was 12.1/100,000 inhabitants. Completeness was 14.0% for IPD-NSS, 35.4% for SMART, and 72.8% for HDRs. The capture–recapture analysis suggested a total estimate of 3419 cases of IPD (95% confidence interval (CI): 1364–5474), corresponding to an underreporting rate of 73.7% (95% CI: 34.0–83.6) for CSS. This study shows substantial underreporting in the Tuscany IPD surveillance system. Integration of available data sources may be a useful approach to complement notification-based surveillance and provide decision-makers with better information to plan effective control strategies against IPD