The Influence of Hyperoxygenation on Fetal Brain Vascularity Measured Using 3D Power Doppler Ultrasound and the Index “Fractional Moving Blood Volume”

<b><i>Introduction:</i></b> Maternal hyperoxygenation effects on fetal cerebral hemodynamics are largely unknown. This study aimed to determine efficacy and reliability of a validated power Doppler ultrasound (US) index, fractional moving blood volume (FMBV), at measuring fetal cerebral vasculature changes during maternal hyperoxia. <b><i>Methods:</i></b> The fetal cerebral effects of 10 min of hyperoxygenation at 2 flow rates (52%/60% FiO₂) were evaluated in women in their third trimester of pregnancy. 2D-US and 3D-US in a transverse plane were performed before, during, and following maternal hyperoxygenation with FMBV estimation performed offline. <b><i>Results:</i></b> Forty-five cases provided data for analysis. Mean intraobserver ICCs were 0.89 (3D-FMBV) and 0.84 (2D-FMBV). A significant difference in vascularity before and during and before and after 60% hyperoxia was observed (<i>p</i> &#x3c; 0.05), whereas no significant differences were found at 52% hyperoxia (<i>p</i> &#x3e; 0.05). Significant differences in vascularity were found between 2D-FMBV and 3D-FMBV (<i>p</i> &#x3c; 0.01). <b><i>Conclusion:</i></b> Measurement of fetal cerebral vascularity by 3D-FMBV and 2D-FMBV was highly reproducible. The differing cerebral vascular changes seen with 60% but not 52% FiO₂ suggest a possible “threshold effect” that may have influenced prior studies. Further studies are needed to assess cerebral effects of maternal hyperoxygenation on compromised fetuses.

Response to Secukinumab on Synovitis using Power Doppler Ultrasound in Psoriatic Arthritis: 12-week Results from a Phase III Study, ULTIMATE

Objectives To investigate the dynamics of response of synovitis to interleukin (IL)-17A inhibition with secukinumab in patients with active psoriatic arthritis (PsA) using Power Doppler ultrasound. Methods The randomised, placebo-controlled, Phase III ULTIMATE study enrolled PsA patients with active ultrasound synovitis, and clinical synovitis and enthesitis having an inadequate response to conventional disease-modifying anti-rheumatic drugs (DMARDs) and naïve to biologic DMARDs. Patients were randomly assigned to receive either weekly subcutaneous secukinumab (300 or 150 mg according to the severity of psoriasis) or placebo followed by 4-weekly dosing thereafter. The primary outcome was the mean change in the ultrasound Global European League Against Rheumatism and Outcome Measures in Rheumatoid Arthritis Clinical Trials Synovitis Score (GLOESS) from baseline to week 12. Key secondary endpoints included American College of Rheumatology 20 and 50 responses. Results Of the 166 patients enrolled, 97% completed 12 weeks of treatment (secukinumab, 99%; placebo, 95%). The primary end point was met, and the adjusted mean change in GLOESS was higher with secukinumab than placebo (−9 [0.9] vs −6 [0.9], difference [95% CI]: −3 [−6; −1]; one-sided p = 0.004) at week 12. The difference in GLOESS between secukinumab and placebo was significant as early as one week after initiation of treatment. All key secondary endpoints were met. No new or unexpected safety findings were reported. Conclusion This unique ultrasound study shows that apart from improving the signs and symptoms of PsA, IL-17A inhibition with secukinumab leads to a rapid and significant reduction of synovitis in PsA patients.

POS0661 RAPID RESPONSE TO BARICITINIB IN PATIENTS WITH RHEUMATOID ARTHRITIS AND AN INADEQUATE RESPONSE TO METHOTREXATE AND AT LEAST ONE BIOLOGIC DMARD: A CLINICAL AND POWER DOPPLER ULTRASOUND STUDY

Background:Baricitinib, an oral Janus kinase (JAK) 1-2 inhibitor, is currently used among biologic DMARDs (bDMARDs) after the failure of methotrexate (MTX) in rheumatoid arthritis (RA). Power Doppler ultrasound (PDUS) is a promising, non-invasive imaging method to assess synovitis in RA: results from numerous studies suggest that it provides additional information to clinical and conventional radiographic examinations.Objectives:The main objective of our study was to evaluate short-term efficacy of Baricitinib in reducing synovitis, using the composite semi quantitative scale (0–3 grades) PDUS synovitis score, developed by the Outcome Measures in Rheumatology– European League Against Rheumatism (OMERACT– EULAR)-Ultrasound Task Force. Moreover both synovial hyperplasia and intrasynovial power Doppler (PD) signal were also scored as single components/parameters on 0-3 scales. Secondary objective was to assess the concordance between patient reported outcomes (PROs), markers of inflammation, physical examination and US.Methods:We enrolled 30 patients fulfilling 2010 ACR and EULAR criteria for RA. All patients had failed at least one anti-TNF. Each patient was prescribed Baricitinib 4 mg/daily at T0, in addition to MTX and/or oral steroids at a dosage ≤ 7, 5 mg/day of Prednisone or equivalent, at T’. All patients were evaluated at baseline (T0) and then after one month (T1), 3 months (T2) and 6 months (T3) of treatment. Swollen and tender joints (out of 28)were evaluated and recorded, as well as patient (PGA) and physician global assessment (PhGA) and pain, expressed in a visual analog scale (VAS). Disease activity was evaluated at each visit using DAS28 (Disease activity score 28), CDAI (Clinical disease activity index)and SDAI(Simplified disease activity index), accompanied by a complete blood count, Erythrocyte sedimentation rate (ESR) and C- reactive protein (CRP) collection. Statistical analysis was performed using GraphPad version 9.0.0. PDUS examination, was carried out by two rheumatologists (PF and CB) blinded to clinical conditions of the patients, using an Esaote Mylab Twice (Genoa, Italy), equipped with a high-frequency (6-18 MHz) linear probe. With standardised Doppler parameters (pulse repetition frequency between 500-750 Hz; Doppler frequency between 7–11.1 MHz). PDUS was performed at each visit bilaterally for 22 joint sites [MCPs 1–5, proximal interphalangeal joints (PIPs) 1–5, wrist, elbow, glenohumeral, knee, tibiotalar, talonavicular and calcaneocuboidal and metatarsophalangeal joints (MTPs) 1–5] for a total of 44 joints for each patient.Results:we observed a reduction of VAS pain (T0 vs, T6<0,0001) PDUS composite score (T0 vs. T6 p<0,0001), Power Doppler (T0 vs. T6 p<0,0001) synovial hyperplasia (T0 vs. T6 p=0,0002), CRP (T0 vs. T6 p<0,0001) and ESR (T0 vs. T6 p <0,0001) was observed in our patients. Accordingly, DAS-28, CDAI and SDAI displayed a significant reduction too (DAS-28: T0 vs. T6 p< 0, 0001; CDAI: T0 vs. T6 p< <0, 0001; SDAI: T0 vs. T6 p= 0, 0003).Conclusion:We investigated the efficacy of Baricitinib in real life, evaluating both from a clinimetric and ultrasound point of view. Baricitinib, demonstrated a significant parallel and fast improvement in VAS, PDUS and CRP was found at follow up assessment as early as one month of therapy. In conclusion, these results demonstrated the short term efficacy of Baricitinib 4mg for up to 6 months and providing a prompt improvement of PROs within the first weeks of treatment.Figure 1.The difference between the means of PD and of the VAS pain over time (T0, T1, T3 and T6). Power Doppler (T0 vs. T6** p<0,0001), VAS: (T0 vs. T1 *p<0,0098;T0 vs. T3 **** p<0,0001; T0 vs. T6 ****p<0,0001)Disclosure of Interests:None declared

POS0869 PREDICTIVE VALUE OF ANTI-INTERFERON-INDUCIBLE PROTEIN 16 ANTIBODIES FOR DIGITAL ULCERS OF SYSTEMIC SCLEROSIS

Background:Interferon-inducible protein 16 (IFI-16) is constitutively expressed in vascular endothelial cells and can inhibit the proliferation of human endothelial cells and the formation of capillary-like structures in vitro. Anti-IFI-16 antibodies were reported in 21%-29% of patients with systemic sclerosis (SSc) and were associated with digital vascular events in a few retrospective studies.Objectives:To evaluate the presence and the clinical implication of anti-IFI-16 antibodies in Chinese SSc cohort, focusing on the associations with vasculopathy indexes, and to investigate the predictive value of anti-IFI-16 antibodies for the development of digital ulcers (DUs) in SSc prospectively.Methods:Patients with SSc presenting to our center between July 2018 and September 2018 were prospectively enrolled. Serum from 42 SSc patients and 42 age- and sex-matched healthy controls were analyzed for anti-IFI-16 antibodies by enzyme-linked immunosorbent assay (ELISA), and was considered positive if the optical density (OD) value was above the mean OD of controls plus two standard deviations. Tissue immunofluorescence was used to evaluate the expression of IFI16 in skin biopsy samples obtained from SSc patients and normal controls. At baseline, nailfold video-capillaroscopy was performed to assess nailfold capillary density of SSc patients. Power Doppler ultrasound was used to grade finger pulp blood flow (0-no observed flow; 1-decreased flow; 2-normal flow), and to measure ulnar and radial artery blood flow and resistive index (RI). All patients were followed up for 6 months to see whether they experienced new onset or recurrent DUs. The association of anti-IFI-16 antibodies with DUs was analyzed using logistic regression.Results:Of the 42 SSc patients, 8 (19.0%) were positive for anti-IFI-16 antibodies. Immunofluorescence of skin biopsy samples from SSc patients exhibited enhanced staining of IFI-16 in the dermis, and colocalization with endothelial marker CD31. SSc patients who were positive for anti-IFI-16 antibodies showed higher ulnar artery RI at baseline (0.95±0.09 vs. 0.86±0.09, p=0.015), while no significant differences were found for other vascular parameters, nor for clinical or demographic profiles. Within 6-month follow-up, 14 (33.3%) patients experienced new-onset or recurrent DUs. Univariate logistic regression revealed the presence of DUs at enrollment (p=0.009), anti-IFI-16 antibody (p=0.012), finger pulp blood flow (p=0.027), and ulnar artery RI (p=0.008) could be the predictors for the development of DUs. Multivariate analysis further identified DUs at enrollment (odds ratio [OR]: 10.85; 95% confidence interval [CI]: 1.61-73.18; p=0.014) and anti-IFI-16 antibody (OR: 15.00; 95% CI: 1.13-199.18; p=0.040) as independent risk factors. Among patients without DUs at enrollment, new-onset ulcers occurred in 80% (4/5) and 4.5% (1/22) of those with and without anti-IFI-16 antibody, respectively (p=0.001).Conclusion:Anti-IFI-16 antibody is associated with vasculopathy in SSc and could be used as a novel biomarker for indicating the development of DUs.References:[1]McMahan ZH, Shah AA, Vaidya D, et al. Anti-interferon-inducible protein 16 antibodies associate with digital gangrene in patients with Scleroderma. Arthritis Rheumatol. 2016; 68(5): 1262-71.[2]McMahan ZH, Cottrell TR, Wigley FM, et al. Autoantigens targeted in scleroderma patients with vascular disease are enriched in endothelial lineage cells. Arthritis Rheumatol. 2016; 68(10): 2540–49.Figure 1.Multivariate logistic analysis for new or recurrent digital ulcers.Acknowledgements:The authors would like to thank Doctor Yi Cheng for performing Power Doppler ultrasound assessment.Disclosure of Interests:None declared