EVALUATION OF RESPONSE TO ADJUVANTED RECOMBINANT ZOSTER VACCINATION IN PATIENTS WITH RHEUMATOID ARTHRITIS RECEIVING UPADACITINIB: RESULTS FROM A RANDOMIZED TRIAL SUB-STUDY

BackgroundUpadacitinib (UPA) is an oral JAK inhibitor (JAKi) approved for the treatment of RA. JAKi have been associated with an elevated risk of herpes zoster (HZ) in patients (pts) with RA. The adjuvanted recombinant zoster vaccine (RZV, Shingrix) was shown to be well-tolerated and effective in preventing HZ in adults aged ≥ 50 years.[1] The efficacy and safety of RZV have not been studied in pts with RA while on UPA in combination with MTX.ObjectivesTo assess the immunogenicity of RZV in pts with RA receiving UPA 15 mg once daily (QD) with background MTX.MethodsEligible adults aged ≥ 50 years with RA enrolled in the ongoing SELECT-COMPARE phase 3 trial (NCT02629159) received two RZV doses, administered at the baseline and week (wk) 12 visits. Pts should have been on stable doses of UPA 15 mg QD and background MTX for ≥ 8 wks before the first vaccination and ≥ 4 wks after the second vaccination. Antibody titers were collected pre-vaccination (baseline), 4 wks post-dose 1 vaccination (wk 4), and 4 wks post-dose 2 vaccination (wk 16). The primary endpoint was the proportion of pts with a humoral response to RZV defined as ≥ 4-fold increase in pre-vaccination concentration of anti-glycoprotein E [gE] titer levels at wk 16. Secondary endpoints included humoral response to RZV at wk 4 and the geometric mean fold rise (GMFR) in anti-gE antibody levels at wks 4 and 16. Cell-mediated immunogenicity to RZV was an exploratory endpoint evaluated by the frequencies of gE-specific CD4+ [2+] T cells (CD4+ T cells expressing ≥ 2 of 4 activation markers: IFN-γ, IL-2, TNF-α, and CD40 ligand) measured by flow cytometry at wks 4 and 16 in a sub-cohort of pts.ResultsOf the 95 pts who received ≥ 1 RZV dose, 93 (98%) received both RZV doses. Pts had a mean (standard deviation) age of 62.4 (7.5) years. The median (range) disease duration was 11.7 (4.9–41.6) years and duration of UPA exposure was 3.9 (2.9–5.8) years. At baseline, all but 2 pts were receiving concomitant MTX and half (50%) were taking an oral corticosteroid (CS) at a median daily dose of 5.0 mg. One pt discontinued UPA by wk 16. Blood samples were available from 90/93 pts. Satisfactory humoral responses to RZV occurred in 64% (95% confidence interval [CI]: 55–74) of pts at wk 4 and 88% (81–95) at wk 16 (Figure 1). Age (50–< 65 years: 85% [95% CI: 75–94];≥ 65 years: 94% [85–100]) and concomitant CS (yes: 87% [77–97];no: 89% [80–98]) use at baseline did not affect humoral responses at wk 16. GMFR in anti-gE antibody levels compared with baseline values were observed at wks 4 (10.2 [95% CI: 7.3–14.3]) and 16 (22.6 [15.9–32.2]). Among the sub-cohort of pts, nearly two-thirds achieved a cell-mediated immune response to RZV (wk 4: n = 21/34, 62% [95% CI: 45–78];wk 16: n = 25/38;66% [51–81]). Within 30 days post-vaccination of either RZV dose, no serious adverse events (AEs) (Table 1) or HZ were reported. AEs that were possibly related to RZV were reported in 17% of pts. One death occurred more than 30 days after wk 16 due to COVID-19 pneumonia.ConclusionMore than three-quarters (88%) of pts with RA receiving UPA 15 mg QD on background MTX achieved a satisfactory humoral response to RZV at wk 16. In a subgroup of pts, two-thirds (66%) achieved a cell-mediated immune response to RZV at wk 16. Age and concomitant CS use did not negatively affect RZV response.Reference[1]Syed YY. Drugs Aging. 2018;35:1031–40.Table 1. Safety Results Through 30-Days Post-RZV Vaccination in UPA-Treated PatientsEvent, n (%)UPA 15 mg QD (N = 95)Any AE38 (40%)AE with reasonable possibility of being related to UPAa13 (14%)AE with reasonable possibility of being related to RZVa16 (17%)Severe AEb1 (1%)Serious AE0AE leading to discontinuation of UPA0Death0AE, adverse event;QD, once daily;RZV, adjuvanted recombinant zoster vaccine;UPA, upadacitinib.aAs assessed by the investigator.bHypersensitivity.AcknowledgementsAbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, review, and approval of the . All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Julia Zolotarjova, MSc, MWC, of AbbVie.Disclosure of InterestsKevin Winthrop Consultant of: AbbVie, AstraZeneca, BMS, Eli Lilly, Galapagos, Gilead, GSK, Novartis, Pfizer, Regeneron, Roche, Sanofi, and UCB, Grant/research support from: AbbVie, AstraZeneca, BMS, Eli Lilly, Galapagos, Gilead, GSK, Novartis, Pfizer, Regeneron, Roche, Sanofi, and UCB, Justin Klaff Shareholder of: AbbVie, Employee of: AbbVie, Yanxi Liu Shareholder of: AbbVie, Employee of: AbbVie, CONRADO GARCIA GARCIA: None declared, Eduardo Mysler Speakers bureau: AbbVie, Amgen, AstraZeneca, BMS, Eli Lilly, GlaxoSmithKline, Pfizer, Roche, and Sandoz, Consultant of: AbbVie, Amgen, AstraZeneca, BMS, Eli Lilly, GlaxoSmithKline, Pfizer, Roche, and Sandoz, Alvin F. Wells Consultant of: AbbVie, Amgen, BMS, Eli Lilly, Novartis, Pfizer, and Sanofi, Xianwei Bu Shareholder of: AbbVie, Employee of: AbbVie, Nasser Khan Shareholder of: AbbVie, Employee of: AbbVie, Michael Chen Shareholder of: AbbVie, Employee of: AbbVie, Heidi Camp Shareholder of: AbbVie, Employee of: AbbVie, Anthony Cunningham Consultant of: GSK, Merck Sharp & Dohme, and BioCSL/Sequirus.

Evaluation of the ePlex Respiratory pathogen panel 2 to detect viral and bacterial pathogens, including SARS-CoV-2 Omicron in nasopharyngeal swabs

The simultaneous detection and specific identification of multiple pathogens from patients exhibiting respiratory symptoms is important for directing pathogen-specific treatments. The ePlex Respiratory Pathogen Panel 2 (ePlex RP2 panel) is a multiplex molecular test for the qualitative detection of many viral and bacterial pathogens including SARS-CoV-2 in respiratory tract infections. The ePlex RP2 panel received FDA emergency use authorization for nasopharyngeal swab specimens collected in viral transport media. In the evaluation using the ePlex RP2, a total of 67 nasopharyngeal swab specimens were compared to the ePlex RP panel and the CDC 2019-nCoV Real-Time RT-PCR assay as the reference methods. The overall agreement of the ePlex RP2 panel was 100%. The ePlex RP2 panel could detect Omicron BA1 and BA2. The ePlex RP2 panel is a rapid, sensitive and specific "specimen-to-answer" platform to detect simultaneously multiple viruses and bacteria in the upper respiratory tract.Copyright © 2022 The Authors

The role of trade in pacific food security and nutrition

The Pacific region is experiencing a non-communicable disease epidemic largely driven by an ongoing nutrition transition from nutrient rich whole foods to imported staples and highly processed foods. Food trade is a major driver of this transition. We characterize regional and sub-regional trade from 1995 to 2018 for 18 Pacific Island Countries and Territories using the Pacific Food Trade Database. The analysis shows the growing dependence on imports of rice from South-East Asia and wheat from Australia, and recent growth in imports of meat from Australia, New Zealand and USA, and highly processed foods from South-East Asia. Findings are discussed in terms of policy and trade agreements, and global shocks including COVID-19 and the war in Ukraine.

The role of trade in pacific food security and nutrition

The Pacific region is experiencing a non-communicable disease epidemic largely driven by an ongoing nutrition transition from nutrient rich whole foods to imported staples and highly processed foods. Food trade is a major driver of this transition. We characterize regional and sub-regional trade from 1995 to 2018 for 18 Pacific Island Countries and Territories using the Pacific Food Trade Database. The analysis shows the growing dependence on imports of rice from South-East Asia and wheat from Australia, and recent growth in imports of meat from Australia, New Zealand and USA, and highly processed foods from South-East Asia. Findings are discussed in terms of policy and trade agreements, and global shocks including COVID-19 and the war in Ukraine.

Experience with tumour necrosis factor-alpha inhibitors for the treatment of cardiac sarcoidosis in a UK medical centre

P217 Table 1Case series outcomes table Case no. IFX dose& regime Follow-up duration (months) Change in prednisolone dose Change in FDG-PET uptake Change in LV systolic function Change in arrythmia burden Adverse events Composite Endpoint Dose pre-IFX(mg) Dose post-IFX(mg) Pre-IFX Post-IFX LVEF pre-IFX (%) LVEF post-IFX(%) Pre-IFX Post-IFX Infections Heart failure VT/VF (requiring device) All-cause mortality Aborted SCD (device) Cardiac Transplant Case 1 IFX 3 mg/kg every 8 weeks (break after 10th dose due to covid pandemic;restarted 3 months later) 29 20 15 Active CS(SUVmax 11.1) Improvement(SUVmax3.5) 58 59 N/A N/A 0 0 0 0 0 0 Case 2 IFX 3 mg/kg every 8 weeks. Stopped after 15.6 months due to resolution 15.6 10 10 Active CS(SUVmax 10.2) Improvement(SUVmax 2.65) 55 62 VA 0 1 (chest infection) 0 0 0 0 0 Case 2Relapse (7 months after stopping IFX) due to VT and FDG uptake IFX 3 mg/kg every 8 weeks 12 10 10 Active CS(SUVmax 3.3) Improvement(no uptake) N/A 50 VA 0 0 Mild LVSD 0 0 0 0 Case 3 IFX 3 mg/kg0 weeks and 4 weeks;missed 8 weeks’ appointment due to COVID-19 10 20 20 Active CS(SUVmax 11.3) N/A 55 N/A 0 N/A 1 (Covid-19) 0 0 0 0 0 Case 4 IFX 3 mg/kg at 0, 2 and 8 weeks afterwards 16 20 10 Active CS(SUVmax 13) Improved(SUVmax 3.4) 45 66 VA N/A 0 0 0 1 (PFO and shunt/complications) 0 0 Case 5 IFX 3 mg/kg 0, 2, 6 and every 8 weeks 8.5 30 15 Active CS(SUVmax 11.3) Improved(no uptake) 46 51 VA 0 0 0 0 0 0 0 Totals 6 IFX 3 mg/kg Mean=15.2 Mean=18.3 Mean=13.3 All had active CS 5 improved;1 data not available Mean=51.8 Mean=57.6 4 had VAs;1 data not available None had VA;3 had data not available 2 1 0 1 0 0 CS = cardiac sarcoidosis;FDG-PET =fluorodeoxyglucose positron emission tomography;IFX = Infliximab;LV = left ventricular;LVEF = left ventricular ejection fraction;LVSD = left ventricular systolic dysfunction;N/A = data not available;PFO= patent foramen ovale;

Donation after circulatory death liver transplants are higher and unevenly distributed in the United States after the implementation of the acuity circle allocation policy

Background: This study aimed to assess the impact of the recently (02/2020) implemented Acuity Circles (AC) liver allograft allocation policy on MELD at transplant and Donation after Circulatory Death (DCD) rates. Methods: Study period: 01/2016- 08/2021. Data retrieved from SRTR database. Inclusion criteria: All DCD liver transplants (LT). The cohort was dichotomized into a pre- and post-AC era. DCD rate (defined as DCD/ 50k population/year) was calculated for each State. The change (Δ) on the DCD rate (ΔDCD) and the MELD (ΔMELD) between the two periods was also calculated. Results: 1. Total LT increased in the post-AC era (26%/50k vs. 15%/50k, p=0.0567). 2. DCD LT increased in the post-AC era (15%/50k vs.10%/50k, p=0.0885). 3. MELD increased in the post-AC era in nearly all States (ΔMELD, fig.1, 2 & 3). 4. Uneven distribution of pre- & post-AC DCD activity, with a few States driving DCD LT in the US (fig.4 & 5). 5. Arizona and Louisiana had the highest pre-AC DCD rates (58%/50k & 31%/50k, respectively;fig.3). 6. The top post-AC DCD rate was reached in Arizona (78%/50k, fig.5). 7. Top post-AC ΔDCD was noted in Arkansas & Arizona (fig.6). 8. The highest ΔMELD was noted in low DCD/ negative ΔDCD areas (fig.7). 9. The lowest ΔMELD was noted in areas with the highest DCD rate (fig.7) 10. The State with the highest DCD rates pre-AC had the highest ΔDCD (fig.5). 11. 10/11 States with negative ΔDCD were located North of the 35o. Conclusions: AC implementation coincided with an increase in the overall LT & DCD LT activity. However, causation remains to be clarified, given the concurrent opioid crisis and SARS-CoV-2 pandemic. There was remarkable DCD rate variation. States with high DCD rates/ΔDCD demonstrated greater adaptability in the allocation change, maintaining low ΔMELD across eras. (Figure Presented).

Lung cancer screening provides a unique opportunity for early diagnosis and management of interstitial lung diseases

P4 Table 1Characteristics of the subjectsCharacteristics Subjects with ILAs on LDCT (n = 39) Age, yr, mean (± SD) 68.8 (± 4.3) Gender, n (%) Female 15 (38.5) Male 24 (61.5) Smoking status, n (%) Current 7 (17.9) Ex 32 (82.1) Respiratory symptoms, n (%) None 19 (48.7) Cough 3 (7.7) Dyspnoea 9 (23.1) Cough & dyspnoea 6 (15.4) N/A 2 (5.1) Physical examination findings, n (%) None 5 (12.8) Crackles 17 (43.6) N/A 17 (43.6) Baseline lung function,%pred, median (range) FEV1,% pred 91 (58 – 130) FVC,% pred 94.8 (65 – 143) TLco,% pred 57.6 (28.4 – 98.8) Kco,% pred 79.5 (36.4 – 94) MDT Diagnosis ILAs, n (%) 8 (20.5) ILD, n (%) IPF 14 (35.9) Smoking-related ILD 6 (15.4) Hypersensitivity pneumonitis 4 (10.3) PPFE 3 (7.7) Sarcoidosis 1 (2.6) Post-COVID ILD 1 (2.6) Vasculitis 1 (2.6) Unclassifiable 1 (2.6) Treatment, n (%) Smoking cessation advice 6 (15.4) Antifibrotic 7 (17.9) Immunomodulatory treatment 2 (5.1) None 23 (59) ResultsILAs of >5% extent on LDCT were identified in 39/1853 (2.1%) subjects screened between August 2018 and April 2021 (table 1). Respiratory symptoms were present in 18/39 (46.1%) and crackles were auscultated in 17 of 22 subjects (77.3%) undergoing physical examination. Past exposure to potential environmental triggers was noted in 21/39 (53.8%). Diagnostic bronchoalveolar lavage was performed in 7/39 (17.9%) and one patient underwent transbronchial lung cryobiopsy. After MDT discussion, ILD was concluded in 31/39 (79.5%) cases, of which 14/31 (45.2%) were diagnosed with IPF. In the IPF subgroup, antifibrotics were initiated in 7/14 (50%) of cases. In those diagnosed with other ILDs, immunomodulatory treatment was initiated in 2/25 (8%) subjects.ConclusionA large proportion of individuals with newly identified ILAs have an abnormal clinical examination and respiratory symptoms, consistent with the widely held suspicion that ILD is underdiagnosed in the community. Lung cancer screening in this demographic provides a unique opportunity to address this unmet health metric. Earlier identification of ILD, specifically IPF, allows institution of antifibrotic therapies proven to modify the natural history of the disease by preserving lung function and extending life. The cost-effectiveness of this approach for ILD screening warrants detailed evaluation.

Respiratory and intestinal epithelial cells exhibit differential susceptibility and innate immune responses to contemporary EV-D68 isolates

Background: Enterovirus D68 (EV-D68) has been implicated in outbreaks of severe respiratory illness and associated with acute flaccid myelitis (AFM), a disease which causes paralysis in previously healthy patients, mostly children. AFM peaked in even numbered years, at least 2014-2018. While 2020 was expected to be a peak AFM year, few cases were seen, likely due to non-specific social distancing measures due to SARS-CoV-2. EV-D68 is primarily described as a respiratory pathogen, in contrast to 'classic' enteroviruses that are spread via the fecal-oral route. However, similar to other enteroviruses, EV-D68 has been detected in wastewater, suggesting it might also have an enteric route of transmission.