Efficacy and safety of bovhyaluronidase azoximer (Longidase) in patients with post-COVID syndrome: results of an open, prospective, controlled, comparative, multicenter clinical trial DISSOLVE.

Post-COVID syndrome develops after COVID-19 (COronaVIrus Disease 2019) and leads to cumulative effects in the form of shortness of breath and impaired lung function. Notably, patients with airway inflammation and COVID-19 were found to have increased concentrations of hyaluronic acid (HA). Since bovhyaluronidase azoximer (Longidase) catalyzes the hydrolysis of HA, this drug has the potential to reduce HA levels and improve lung function in patients with post-COVID syndrome. The aim of the DISSOLVE trial, which was conducted early in the pandemic, was to investigate the efficacy and safety of bovhyaluronidase azoximer in patients with symptoms associated with post-COVID syndrome. Methods. An open, prospective, controlled, comparative, multicenter clinical trial (NCT04645368) included adult patients (n = 160) who had post-COVID syndrome. Patients in the treatment group (n = 81) received bovhyaluronidase azoximer, and individuals in the control group (n = 79) were followed up without intervention. The study included physical examination, evaluation of forced vital capacity (FVC), assessment of dyspnea with the Modified Medical Research Council Dyspnea Scale (mMRC), 6-minute walking test, and pulse oximetry. These indicators were measured on 3 visits, at days 1 (baseline), 75, and 180. In addition, the number of patients who experienced adverse events and serious adverse events were recorded. Results. Baseline patient characteristics in the treatment group and the control group were similar. In the treatment group, there was a statistically significant reduction in residual pulmonary abnormalities after visit 2 (day 75) and visit 3 (day 180). In addition, FVC, pulse oximetry values, and functional exercise tolerance increased statistically significantly at days 75 and 180 compared to baseline. The mMRC scores for dyspnea decreased statistically significantly in the treatment group over 75 days. The safety profile of the drug was reported to be favorable throughout the study. Conclusion. Treatment with bovhyaluronidase azoximer in patients with post-COVID syndrome showed improvement in FVC, pulse oximetry, functional exercise tolerance, and mMRC dyspnea.Copyright © Chuchalin A.G. et al., 2023.

Efficiency of application of sorbed probiotics in the complex therapy of pneumonia caused by SARS-CoV-2. Quality of life in the short term COVID-19

Aim. To determine the clinical efficacy and safety of the immobilized (sorbed) probiotics Bifidobacterium bifidum 1 (5x108 CFU) and B. bifidum 1 (5x107 CFU) in combination with Lactobacillus plantarum 8P-A3 (5x107 CFU) in the complex therapy of pneumonia caused by SARS-CoV-2 in adult patients without severe risk factors and their impact on health-related quality of life (QoL). Material and methods. An open, randomized prospective study included 100 patients (45 males, 55 females), aged from18 to 60 years without risk factors for severe COVID-19, with pneumonia confirmed by computed tomography and an area of lung lesion no more than 75% (moderate forms). SARS-CoV-2 RNA in nasal and oropharyngeal swabs (RT-PCR) was detected in 72% of the participants, in the rest it was highiy probable in terms of the aggregate parameters. The publication presents the results of self-assessment (94 respondents) of working capacity limitations, shortness of breath, intestinal disorders since the end of the probiotic regimen (PR: hospitalization period - B. bifidum 1, 3 capsules 2 times a day for 10 days, then after hospitalization - B. bifidum 1 in combination with L. plantarum 8P-A3 2 powders 3 times a day for 14 days) and QoL (Short Form Medical Outcomes Study: SF-36) 1 month after hospitalization. Results. At the end of PR, the ability to engage in daily activities was higher by 23.1% [95% confidence interval 5.3-37.3, OR 0.08 (0.08-0.77)]. Difficulty of breathing during exercise was less common by 29.7% [15.1-44.5%], OR 0.09 [0.02-0.40], hard stools and no bowel movements were recorded less often by 21.3% [8.5-34, 1] for 1-3 days. One month after hospitalization, the QoL of the patients receiving standard treatment was significantly reduced relative to population indicators in Russia. It was more significantly due to the psychological component of health [total measurement 38.1 (36.2-40.0)] and less significantly due to the physical component [49.5 (48.3-50.8)]. The main reasons limiting daily activities [Role Emotional (RE): 39.4 (37.4-41.4)] were decreased vitality [VT: 40.2 (38.9-041.5)], emotional depression [Mental Health (MH): 41.2 (39.4-43.0)], deficit of social contacts [Social Functioning (SF): 45.1 (43.7-46.6)]. The patients who received PR had a higher ability to carry out daily activities [RE: 57.7 (55.6-59.7)], the severity of psychological problems associated with fatigue, anxiety and depression was lower [MH: 59.8 (58.7-60.9), p<0,001]. The effect of the PR on negative perceptions of social isolation was comparatively less [SF: 53.9 (52.2-55.4)]. The QoL of the patients who additionally suffered from diarrhea in the acute period of SARS-CoV-2 pneumonia was worse in comparison with the patients without diarrhea (due to pain and inability to endure physical activity). The effects of immobilized (sorbed) probiotics to the QoL of the patients with diarrhea during the acute period of COVID-19 were most significant. Conclusion. PR had a significant positive effect on the QoL within a month after hospitalization, increasing working capacity and improving mental health, reducing the severity of psychological problems and fatigue. Additional researches are needed on the possible relationship of organic and functional gastrointestinal diseases with the progression of diarrhea in patients infected with SARS-CoV-2. No side effects of the sorbed probiotics regimen have been identified.Copyright © Eco-Vector, 2022.

Effectiveness of Colchicine among Patients with Covid-19 Infection: A Randomised, Open Labelled, Clinical Trial

Background/Aims In November 2019, there were abundant cases of COVID-19 for which the first case was reported in Wuhan, China. Cytokine storm syndrome is the severe immune reaction that may cause a severe tissue response in COVID-19 patients. Colchicine has an important role in inhibiting activation of NLRP3 inflammasome that predispose to decrease cytokine production. This study aimed to evaluate whether colchicine is effective in treatment of COVID-19 patients or not. Methods A randomized, open labelled, clinical trial of colchicine for the treatment of COVID-19, allocated between 8th May to 18th June 2021. Patients with mild, moderate, or severe COVID-19 infection;confirmed by real time PCR (RT-PCR) and/or lung involvement confirmed by computed tomography scan compatible with COVID- 19. The colchicine tablet dosage was 0.5mg twice daily for 14 days added to the standard treatment versus control group who received standard treatment without colchicine, with the trial registration ID: NCT04867226. The study was conducted in Erbil City, Iraq with the endpoints being clinical, laboratory parameters duration of hospitalization and side effects. Results 80 patients participated in the study. Fewer patients in the colchicine group had musculoskeletal symptoms (17.5%, p: 0.001) in comparison to the patients, who received control treatment. The serum ferritin level in most of patients who treated with colchicine returned to normal in contrast to the control group, whose serum ferritin level was still high (p: 0.041). Similarly, the average of CRP and D-dimer after treatment among the colchicine group participants was significantly lower than the control group, the P-values were 0.011 and 0.043, respectively. The colchicine group patients stayed for a shorter duration at the hospital (18.4 days) compared to the control group (24.24 days). Pvalue was 0.009. In addition to that the response and cure rate were higher in the colchicine group (56%) in the comparison to control group (43.1%) Table 1: Laboratory Parameters with musculoskeletal symptoms and duration of hospitalization of both Treatment Regimens. Conclusion The colchicine drug can be effective in treating patients with COVID-19 infection by improving musculoskeletal symptoms and inhibiting inflammatory biomarkers;it is also effective in reducing duration of hospitalization. (Table Presented).

Experimental and Clinical Evaluation of Mefloquine Effectiveness against the Infection Caused by Sars-Cov-2

The efficacy of mefloquine has not been studied in the in vivo experiments and clinical trials involving COVID-19 patients. The study was aimed to assess the effects of mefloquine on the SARS-CoV-2 accumulation in the lungs of infected animals and to study the efficacy and safety of mefloquine compared to hydroxychloroquine in patients with COVID-19. During the experiment, a total of 96 Syrian hamsters were infected with SARS-CoV-2. Accumulation of the virus in lungs was compared in the groups of animals treated with mefloquine and ribavirin and in the control group. During the clinical trial, the mefloquine and hydroxychloroquine safety and efficacy in patients with mild and moderate COVID-19 (172 individuals) was assessed based on the symptom changes over time and the computed tomography results. The experiment showed that the SARS-CoV-2 accumulation in the lungs of Syrian hamsters 6 days after infection and mefloquine treatment was 2.2 +/- 0.18 lg PFU/g, which was lower (p < 0.05) than in the control group (3.5 +/- 0.21 lg PFU/g) and ribavirin group (5.2 +/- 0.05 lg PFU/g). During the clinical trial, it was found that 50.0% of patients in the mefloquine group and 32.4% in the hydroxychloroquine group (p < 0.05) developed a mild disease, and the completely resolved respiratory failure was registered in 76.5% and 44.6%, respectively (p < 0.001). Adverse events were observed in 86.7 % and 77% of patients in the mefloquine and hydroxychloroquine groups, respectively (p > 0.05). Thus, during the experiment, mefloquine contributed to the faster virus titer reduction in the lungs. During the clinical trial, the mefloquine efficacy was non-inferiority or, based on a number of indicators, higher compared to hydroxychloroquine, with comparable safety.Copyright © Extreme Medicine.All right reserved.

British Society for Rheumatology Annual Conference 2023 Abstracts

The proceedings contain 343 papers. The topics discussed include: implementation of a disease modifying anti-rheumatic drug blood monitoring software: 8 years of experience in a single center;effectiveness of colchicine among patients with COVID-19 infection: a randomized, open labelled, clinical trial;rheumatic autoimmune diseases following COVID-19 infection: an observational study in Iraqi Kurdistan region;COVID-19 in male elite Irish-based athletes at a national sports institute;the effects of a pain management program for patients with an inflammatory arthritis;a retrospective analysis of the effectiveness safety of platelet rich plasma injections in primary osteoarthritis in knee joint, in patients attending a tertiary care hospital, Sri Lanka;a cohort study;do proformas used in fracture liaison service appointments reflect national osteoporosis clinical standards? a content analysis;calcium pyrophosphate dihydrate crystal in operated rheumatoid arthritis of the knee;cardiac amyloidosis: a case series of 31 patients with a comprehensive literature review;scoping review for the application of center of pressure for patient or intervention assessment in rheumatoid conditions;and four SNPs associated with monocyte/macrophage cell lineage uniquely associated with CRPS-1 in discovery and replication cohorts and suggest predisposition to regional osteopenia and digit misperception.

FAVIPIRAVIR IN THE TREATMENT OF MILD CORONAVIRUS INFECTION: RESULTS OF A MULTICENTER OPEN-LABEL, POST-REGISTRATION, NON-INTERVENTIONAL STUDY.

Clinical parameters characterizing the efficacy and safety of favipiravir were examined in a multicenter, non-interventional (before-and-after study design) trial in 264 patients with mild COVID-19. It is shown that on the background of 14-day therapy with favipiravir body temperature normalized, blood oxygen saturation improved, and the frequency of tachycardia detection reduced by 16% (p < 0.0001). A statistically significant decrease by 91,3% (p 0.0001) in the frequency of SARS-nCoV-2 RNA detection in the nasopharyngeal mucosa discharge was revealed. A decrease in the concentration of ferritin (by 69% compared to initial values), blood glucose (by 21%), creatinine (by 10%), C-reactive protein (by 36%) (p 0.0001), and D-dimer by 61% (p = 0.016) was noted. The results of the SF-36 health survey questionnaire revealed a significant (p 0.05) improvement in the quality of life in terms of physical functioning (by 35%), and role functioning associated with physical and emotional state by 107% and 160%, respectively. Analysis of the COV19-QoL questionnaire revealed a decrease by 24% in negative perception of the disease (p < 0,01). Among the identified adverse events, elevated level of ALT (in 39.47% of patients), hyperuricemia (in 28.95% of patients), and elevated AST (in 23.68% of patients) prevailed. All the adverse events occurred with mild or moderate severity. There were no lethal outcomes in the studied sample of patients. The analysis showed a satisfactory level of the tolerability of the treatment.Copyright © 2023 Izdatel'stvo Meditsina. All rights reserved.

RESULTS OF A 12-WEEK OPEN-LABEL, NON-INTERVENTIONAL STUDY OF THE EFFICACY AND SAFETY OF OLOKIZUMAB THERAPY IN PATIENTS WITH RHEUMATOID ARTHRITIS AFTER SWITCHING FROM ANTI-B-CELL THERAPY DURING THE SARS-COV-2 PANDEMIC.

The COVID-19 pandemic has significantly changed the understanding of the safety profile of therapies for immunoinflammatory rheumatic diseases (IRDs). This is primarily due to the negative impact of a number of basic anti-inflammatory drugs (DMARDs) and biological DMARDs on the course and outcomes of a new coronavirus infection. A number of studies have shown that anti-B-cell therapy (rituximab) gave a statistically significant increase in the risk of severe COVID-19 and an increase in mortality. At the same time, the analysis of real clinical practice data dictated the need to establish a number of restrictions on the use of certain classes of biological DMARDs and to search for alternative therapy programs to maintain control over disease activity. Purpose of the study - to evaluate the efficacy and safety of the drug Artlegia (olokizumab), solution for subcutaneous injection, 160 mg/ml - 0.4 ml, manufactured by R-Pharm JSC, Russia) for the treatment of patients with rheumatoid arthritis in real clinical practice after switching with rituximab during the COVID-19 pandemic. Materials and methods. The study included 14 patients with a confirmed diagnosis of rheumatoid arthritis (RA), who were previously on rituximab therapy at a dose of 1000-500 mg twice with an interval of 2 weeks, who received at least one course of therapy with this drug. As RA worsened, patients were switched to olokizumab against the background of standard DMARDs. At 4, 8, 12 weeks after the switch, the severity of pain was assessed on the VAS scale, the number of painful and swollen joints (TJC28 and TSC28), the level of acute phase markers of inflammation, the DAS28 disease activity index calculated using ESR and CRP, and the CDAI (clinical activity index), functional state index HAQ, as well as assessment of the safety profile of therapy. Results. Data analysis was performed using median values (Me) were used for data analysis. A significant decrease of TJC28 was after the injection of olokizumab (Artlegia) in 8 and 12 weeks (Me baseline = 10;Me 8 weeks = 4;Me 12 weeks = 4;p<0.05) and a decrease of TSC28 in 4, 8 and 12 weeks (Me baseline = 9;Me 4 weeks = 3.5;Me 8 weeks = 2.5;Me 12 weeks = 2.0;p<0.05). Laboratory markers of inflammation showed a decrease in CRP and ESR levels after 4 weeks of treatment (CRP: Me baseline = 21, Me 4 weeks = 1 (p<0.05);ESR: Me baseline = 31, Me 4 weeks = 7 (p<0.05)). Positive dynamics persisted at 8 and 12 weeks (CRP: Me 8 weeks = 1, Me 12 weeks = 0;ESR: Me 8 weeks = 4, Me 12 weeks = 5). The level of CRP by the fourth week 4 became within the normal range, regardless of the initial values. All activity indices improved from the fourth week in each evaluation period compared to baseline: DAS28-ESR: Me baseline = 5.52, Me 4 weeks = 3.59, Me 8 weeks = 3.33, Me 12 weeks = 3.22 (p<0.05);DAS28-CRP: Me baseline = 5.39, Me 4 weeks = 3.71, Me 8 weeks = 3.35, Me 12 weeks = 3.45 (p<0.05);CDAI: Me baseline = 28.5, Me 4 weeks = 18.0, Me 8 weeks = 16.5, Me 12 weeks = 16.0 (p<0.05). All patients showed a reduction in pain (VAS scale) by week 8. The functional status of patients, according to the HAQ index, showed a significant decrease only by the 12th week of the study: Me baseline = 1.62, Me 12 weeks = 1.31 (p<0.05). Conclusion. The study found that switching from rituximab to olokizumab was effective and safe during the COVID-19 pandemic.Copyright © 2023 Ima-Press Publishing House. All rights reserved.

First in-neonate use of non-invasive transcutaneous auricular vagus nerve stimulation: 18-month neurodevelopmental and sensory follow-up

Objective: Non-invasive transcutaneous auricular vagal nerve stimulation (taVNS) paired with oral feeding is a novel intervention for infants with feeding delays that may improve feeding and help avoid a gastrostomy tube (Gtube). However, the long-term impact of this neurostimulation on infant's development remains unknown. We investigated the neurodevelopmental and sensory outcomes of infants who received taVNS paired with bottle feeding. Method(s): Twenty-one of 35 toddlers who participated in the open label trial of taVNS paired with one or two feeds a day for 2-3 weeks, underwent comprehensive developmental assessments at 18 months of age using Cognitive Adaptive Test, Clinical Linguistics and Auditory Milestone, and Peabody gross motor scores. Twelve of those assessed achieved full oral feeds ('responders') and 9 had G-tube placed for feeds ('non-responders'). Before COVID, 12 toddlers (5 responders, 7 non-responders) were also assessed in the home using the Bayley-III and Sensory Profile (SP-2) assessments. Area deprivation index (ADI) was used to measure resource poor environments and relate to test scores. We used Fishers exact test and Pearson correlation coefficients to compare neurodevelopmental and sensory performance in responders versus non-responders. Result(s): taVNS responders showed significantly better general sensory processing in SP-2 than did non-responders (p =0.04). There were no significant differences in Bayley-III or CAT/CLAMS/ASQ scores in areas of cognition, receptive language, fine motor, and gross motor skills in this small sample size, but are similar to published scores for preterm infants who received G-tubes. ADI was not significantly associated with neurodevelopmental scores. Conclusion(s): These results suggest that taVNS paired with feeding may have a potential long-term positive neurodevelopmental effect on sensory processing in neonates with poor feeding. The current open-label results need testing in randomized controlled trials of taVNS paired with oral feeding in developmentally delayed infants failing oral feeds. Research Category and Technology and Methods Clinical Research: 12. Vagus Nerve Stimulation (VNS) Keywords: Neurodevelopment, taVNS, feeding, developmental delaysCopyright © 2023

High dietary iodine intake may contribute to the low death rate from COVID-19 infection in Japan with activation by the lactoperoxidase system

We draw the attention of readers and governments to the death rate from coronavirus disease 2019 in Japan, continuing as a fraction of that experienced by many other developed nations. We think this is due to the activity of the powerful, protective lactoperoxidase system (LPO) which prevents serious airborne infections. The LPO system requires iodine, which is liberally provided by the typical Japanese diet but lacking in many others. One might consider the Japanese experience an incredibly large, open-label study exhibiting the preventative power of a high-iodine diet. We predict this favourable trend will continue for Japan because deadly variants of the severe, acute respiratory syndrome coronavirus 2 will be with us, forever.Copyright © 2023 The Scandinavian Foundation for Immunology.

Efficacy of Breathox device inhalation on acute symptoms associated with COVID-19 (BREATH study)

Background: Breathox is a sodium chloride inhaler. Increase of the airway salinity has been proposed to reduce the symptomatic stage of a respiratory viral infection. Objective(s): to evaluate the effectiveness of nasal and inhaled sodium chloride therapy through Breathox on mild COVID-19 symptoms in patients >= 18 years-old compared to usual care. Method(s): a pilot, open, randomized clinical trial, including 100 patients with confirmed and symptomatic COVID-19 within 10 days of symptom onset. All patients received standard of care (SOC), i.e. antipyretic or analgesic. Breathox was administered as two oral inhalations and one nasal instillation in each nostril at each administration with 2mg per inhalation. Patients were randomized 1:1:1 into three groups: Group 1(G1): SOC + Breathox 10 times daily for 10 days;Group 2(G2): SOC + Breathox five times daily for 10 days;Group 3(G3): SOC. Recovery time for symptoms, such as cough was assessed. Result(s): In total 100 of 103 screened patients were included from December 1 2021 to March 03 2022. Of those, 33 from G1 and G3, and 32 from G2 completed the study. Mean age was 40.4/42.2/40.6 years old for G1, G2 and G3, (p=0.96). No patients were hospitalized or died during the study. Time to cough resolution was reduced in G1 (2.8+/-0.66 days) and G2 (2.4+/-0.66 days) compared to G3 (5.39+/-0.79 days) (p=0.001), with a hazard ratio (HR) for G2 of 2.17 (Confidence interval 1.17-4.04) and G3 of 2.01 (1.06-3.81) compared to SOC. Conclusion(s): ten days of Breathox use halved the time for resolution of COVID-19-induced cough.

Efficacy and safety of ivermectin in patients with mild and moderate COVID-19: A randomized controlled trial

Objective: To evaluate the effectiveness and safety of ivermectin in patients with mild and moderate COVID-19. Method(s): This study was a single-center, randomized, open-label, controlled trial with a 2-arm parallel-group design on 68 patients with COVID-19. According to the 1:1 ratio between the study groups (ivermectin group and standard treatment group), patients were randomly admitted to each intervention arm. Result(s): The mean age of the participants in the ivermectin group was (48.37+/-13.32) years. Eighteen of them were males (54.5%) and the participants in the control group had a mean age of (46.28+/-14.47) years, with nineteen of them being males (59.4%). As a primary outcome, after 5 days of randomization, there was no significant difference between the ivermectin group and the control group in the length of stay in the hospital (P=0.168). ICU admission (P=0.764), length of stay in ICU (P=0.622), in-hospital mortality (P=0.427), adverse drug reactions, and changes in the mean difference of laboratory data had not any significant difference between the two groups (except for urea change). In addition, the radiologic findings of the two groups of patients were not significantly different. Linear regression analysis showed that for every 10 years increase of age, 0.6 day of hospitalization duration was increased. There was no statistically significant association between other variables and clinical outcomes. Conclusion(s): Among adult hospitalized patients with moderate to severe COVID-19, there was no significant relationship between the administration of ivermectin single dose in a five-day course and clinical improvement, and mortality of the participants.Copyright © 2023 Wolters Kluwer Medknow Publications. All rights reserved.

Single-Dose Bioequivalence Study of Rivaroxaban-Containing Medicinal Products in Healthy Volunteers.

Therapeutically, new oral anticoagulants (NOACs) are considered to be non-inferior or superior to vitamin K antagonists (warfarin). NOACs are included in current guidelines for the treatment of various cardiovascular diseases. Rivaroxaban medicinal products have been shown to effectively fight thrombotic complications of the new coronavirus infection, COVID-19. The wide clinical use of rivaroxaban products motivates the development of generics. The aim of the study was to compare the pharmacokinetics and safety of rivaroxaban medicinal products in a single-dose bioequivalence study in healthy volunteers under fasting conditions. Material(s) and Method(s): the bioequivalence study compared single-dose oral administration of Rivaroxaban, 10 mg film-coated tablets (NovaMedica Innotech LLC, Russia), and the reference product Xarelto, 10 mg film-coated tablets (Bayer AG, Germany), in healthy volunteers under fasting conditions. The open, randomised, crossover trial included 46 healthy volunteers. Each of the medicinal products (the test product and the reference product) was administered once;blood samples were collected during the 48 h after the administration. The washout between the study periods lasted 7 days. Rivaroxaban was quantified in plasma samples of the volunteers by high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). Result(s): no adverse events or serious adverse events were reported for the test and reference products during the study. The following pharmacokinetic parameters were obtained for Rivaroxaban and Xarelto, respectively: Cmax of 134.6 +/- 58.0 ng/mL and 139.9 +/- 49.3 ng/mL, AUC0-48 of 949.7 +/- 354.5 ngxh/mL and 967.6 +/- 319.9 ngxh/mL, AUC0- of 986.9 +/- 379.7 ngxh/mL and 1003.6 +/- 320.4 ngxh/mL, T1/2 of 8.2 +/- 3.2 h and 7.8 +/- 3.3 h. The 90% confidence intervals for the ratios of Cmax, AUC0-48, and AUC0- geometric means were 88.04-108.67%, 89.42-104.92% and 89.44-104.81%, respectively. Conclusion(s): the test product Rivaroxaban and the reference product Xarelto were found to have similar rivaroxaban pharmacokinetics and safety profiles. The study demonstrated bioequivalence of the medicinal products.Copyright © 2022 Obstetrics, Gynecology and Reproduction. All rights reserved.

Pharm Aco Kin Etics of Remdesivir and Its Metabolites in Participants with Moderate and Severe Hepatic Impairment

BACKGROUND: Remdesivir (RDV) is an RNA polymerase inhibitor approved for treatment of COVID-19 (200 mg loading dose, 100 mg qd thereafter) in adult and pediatric patients, primarily metabolized by the high-capacity carboxylesterase 1 pathway (80% of metabolism), and by cathepsin A and CYP3A (10% each). The extensive hepatic contribution to RDV elimination and the prevalence of liver comorbidities in COVID-19 patients warranted a study in participants with hepatic impairment (HI). METHOD(S): This is a phase 1, open-label study of RDV consisting of moderate and severe HI participants and healthy matched controls (HMC) based on age (+/- 10 years), sex, and BMI (+/- 20%). Participants received a single 100 mg IV dose of RDV and remained in the clinic for 8 days. The primary endpoint was pharmacokinetic (PK) parameters of RDV and metabolites. RESULT(S): Preliminary PK and safety data from 10 moderate and 6 severe HI participants and their HMC are available. The average PK fold-change for all analytes and matrices assessed in the study are presented (Table). No serious treatment-related adverse events and no clinically significant changes in participant lab values were reported. CONCLUSION(S): The 1.52 RDV AUCinf fold increase is within expected ranges and justifies no dose adjustment in COVID-19 patients with impaired hepatic function. (Table Presented).

133. Should Pediatricians Consider Offering the HPV Vaccine to Mothers Accompanying their Children to Routine Visits?

Purpose: The Food and Drug Administration (FDA) expanded the approved age range for the 9vHPV vaccine from 9-26 years to 9-45 years in 2018. However, research has still pointed to low vaccination rates among adult women. This could likely be due to missed opportunities as they must have aged out and be ineligible for the vaccine prior to the expansion. Therefore, this study assesses a better understanding of patient's (particularly mothers) preferences of receiving the HPV vaccine to provide quantitative estimates of potential vaccine uptake. Methods: We conducted a descriptive questionnaire survey among women participating in an Open-Label Clinical Trial evaluating the Immunogenicity of the 9vHPV Vaccination Regimen over 6 months among women aged 16 to 45 years old. The survey was fielded to a sample of 245 women receiving care at Boston Medical Center, who had not yet received the HPV vaccine. We used a two-sided Fisher's exact test (because >20% of the expected cell count is less than 5) to compare the responses to two closed-ended questions: "If your daughter or son's doctor offered you the HPV vaccine during your child's visit, would you decide to get the vaccine?” and "Would you prefer to receive the HPV vaccine through your primary care physician instead of your child's care doctor?”. The mean and standard deviation (sd) were reported for continuous variables whereas proportions were reported for dichotomous and categorical data. All analyses were performed using SAS (9.4). Results: We had a diverse study population with a mean age of 32 years (sd=7.86), 25.75% were African American, 20.60% were Hispanics, 21.46 % were Asians, 18.88% were White and 13.31% were Others. We used cross tabulation to describe the relationship between the two variables of interest. Results indicate that 85.11% of women are willing to receive the vaccine from their child's doctor;however, are unwilling to receive it through their own primary care provider. Whereas 7.76% women preferred receiving the vaccine from their primary care physician and are unsure or unwilling to get it from their child's doctor. Also, 67.74% of women indicated their willingness to get the vaccine from their child's doctor;however, were unsure about getting it through their primary care physician. We did a two-sided Fisher's exact test of proportions of p < 0.0001 and concluded that there is a statistically significant difference between women who preferred receiving the HPV vaccine through their child's provider and women willing to receive it through their primary care provider (assuming a significance level of 0.05). Conclusions: Our findings suggest that mothers would prefer getting the HPV vaccine for themselves at their child's doctor visit, if it was offered to them. Influenza and Covid vaccines are offered to parents/guardians in pediatric offices, and this should be implemented for HPV vaccine as well. This would increase the vaccination rates, given children tend to have an increased number of visits prior to the adolescent years and parents are likely to accompany their children to these visits. Sources of Support: cdc.gov.

Testing Continued Effectiveness Through Multiple Modifications of an Empirically Supported Treatment for Organization, Time Management, and Planning Deficits in ADHD and Related Disorders

Objectives: Organizational skills training (OST) for youth with ADHD is an efficacious treatment that addresses impairments at home and in school. Modifications of OST were conducted to treat children with or without ADHD, to reduce treatment barriers, and to respond to changes in school demands during the COVID-19 pandemic. Method(s): After an initial RCT documenting OST efficacy, 3 further studies involved: 1) an open replication of the original RCT confirming improvements in organization, time management, and planning (OTMP) in children diagnosed with ADHD (N = 15) using twice-weekly in-person visits;2) a subsequent open trial investigating children with deficient organizational skills with or without ADHD and altering delivery to involve a combination of in-person and virtual meetings (N = 29);and 3) a third study with subjects with low OTMP skills who do not necessarily have ADHD, receive treatment with combined in-person and virtual delivery or, in response to COVID-19 restrictions, fully virtual delivery (N = 27, thus far), and, in response to remote school delivery, have altered OST content to fit varied school instruction demands (eg, use of electronic documents instead of papers) while adhering to the principles of OST. Change was measured on the Children's Organizational Skills Scales (COSS). Result(s): 1) Improvements in OTMP skills (parent ratings d = 3.73;teacher ratings d = 1.12) in the first open study were comparable to the initial RCT findings. 2) In study 2, parents also reported substantial improvements (d = 3.04), and teachers reported large changes (d = 0.88) in pre-post comparisons. 3) In the ongoing RCT, subjects who received treatment immediately were reported to have large changes by parents (d = 2.17) and moderate changes by teachers (d = 0.47) when compared to waitlist controls. Conclusion(s): Initial analyses indicate that OST leads to OTMP improvements in children struggling with disorganization with and without ADHD diagnosis. Improvements are found when treatment is delivered fully in-person, delivered in hybrid in-person and virtual meetings, or delivered fully virtually. OST could help children with or without ADHD improve behavioral and emotional adjustment at home and in school, when treatment delivery is modified to increase treatment availability, and when school demands are varied. ADHD, CBT, EBP Copyright © 2022

Pegloticase for Uncontrolled Gout in Kidney Transplant Recipients: Provisional Data Report of a Multicenter, Open-Label, Efficacy and Safety Study

Purpose: Gout in kidney transplant (KT) recipients can be severe and particularly challenging to manage. Pegloticase co-therapy with immunomodulators improved urate lowering therapy (ULT) response rates over phase 3 monotherapy trials by reducing anti-drug antibodies.1,2 This open-label trial (PROTECT NCT04087720) examined pegloticase safety and efficacy in KT patients with uncontrolled gout. Method(s): KT recipients with uncontrolled gout (serum urate [SU]>=7 mg/dL, intolerance/ inefficacy to ULT and >=1 of the following: tophi, chronic gouty arthritis, >=2 flares in past year) and functioning KT graft (eGFR>=15 ml/min/l.73m2) on stable immunosuppressive (IS) therapy (KT>l year earlier) received pegloticase (8 mg every 2 weeks for 24 weeks). SU response during Month 6 (SU <6 mg/dL for >=80% of time) and Health Assessment Questionnaire (HAQ) pain (most severe: 100) and Disability Index (HAQ-DI, max: 3) scores were evaluated. Patients discontinuing treatment before Month 6 were considered nonresponders. Patients discontinuing due to COVID-19 concerns were excluded from analysis if no data points were available in Month 6. Result(s): 20 patients enrolled (mean+/-SD;age: 53.9+/-10.9 years, 85% male, time since KT: 14.7+/-6.9 years, SU: 9.4+/-1.5 mg/dL, gout duration: 7.9+/-11.6 years;all on >=2 IS) and 14/20 completed treatment. 16/18 (88.9% [95% CI: 65.3, 98.6]) were SU responders vs 43.5% previously reported3 without immunomodulation. Substantial SU reductions during treatments were reported in 18/20 patients completing or discontinuing for non-SU monitoring rule reasons (pre-dose SU>6 mg/dL at 2 consecutive visits). No notable eGFR changes were observed up to 3 months follow-up. In patients completing treatment, HAQ-pain and HAQ-DI mean scores improved by 35.5+/-31.5 and 0.3+/-0.6, respectively, at Week 24 (n=13 and n=14). 7 serious adverse events, deemed unrelated to pegloticase, were reported in 5 patients. No anaphylaxis or infusion reaction events occurred. Conclusion(s): Pegloticase was safe and effective in treated KT patients with uncontrolled gout, achieving a higher durable response rate than in previously-reported patients not on IS therapy along with improved HAQ scores indicative of quality of life impact. These findings are consistent with other reports of immunomodulation with pegloticase.

CLINICALLY MEANINGFUL DATA FROM REMOTE SPIROMETRY MONITORING IN ASTHMA MANAGEMENT IN A US-BASED OBSERVATIONAL STUDY

SESSION TITLE: Unique Uses of Pulmonary Function Tests SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm PURPOSE: Prevention of asthma exacerbations can be done through adequate self management at home. This study aimed to evaluate the feasibility and safety of a portable spirometer for unsupervised home spirometry measurements among patients with asthma. METHODS: A single center, prospective, single-arm, open study recruited 25 patients with moderate or severe asthma. After a 45 min video training session by a respiratory therapist, patients performed daily spirometry at home with the Spirobank Smart MIR mobile spirometry system that was bluetooth connected to the KevaTalk app. Each spirometry examination was recorded and evaluated according to the ATS/ERS acceptability and repeatability criteria. Patients had to perform at least three technically acceptable maneuvers with the KevaTalk app guiding them if they had a good or bad blow. The best value of the three maneuvers were used for subsequent analyses. Patients also entered their daily check ins and symptoms via the KevaTalk Asthma app, tracked their controller and rescue medication use, filled up ATAQ questionnaires as well as were reminded of their action plans. Data obtained from spirometry was reviewed by nurses and pulmonologist and the Keva365 remote monitoring platform prompted alerts based on patient checkins, use of medication and PEF values in the red or yellow zone. Any escalations based on nurse review were reported to the office. RESULTS: Mean age of the patients was 57 years. 1155 spirometry sessions were completed over the duration of 9 months of the study. Data for FEV1, FEV6, PEF FEV1/FVC, as well as the Best Predicted and LLN values was reviewed daily for patients. Flow volume loops during the sessions were reviewed to identify if the home spirometry was done correctly and retraining was provided if needed. The reported values were tracked over the duration the patient was enrolled in the Keva program. 60.9% of patients were found to have peak flows in their respective red zones at least once and 87% were found to have peak flows in their yellow zone at least once, during the course of the study. If 3 consecutive values were in the yellow or red zone along with worsening of symptoms, the physician's office was informed for further course of action. CONCLUSIONS: The COVID-19 pandemic led to paucity of in office spirometry and face-to-face visits for asthmatic patients. Increasing the availability of spirometry with handheld devices along with a remote monitoring platform is useful for improving asthma control and reducing the risk of asthma-related hospital admissions and deaths. CLINICAL IMPLICATIONS: Remote objective spirometry yields clinically meaningful information that helps with asthma patient management and prevent an exacerbation from becoming worse. DISCLOSURES: No relevant relationships by Karim Anis No relevant relationships by Varada Divgi No relevant relationships by Jyotsna Mehta No relevant relationships by Shail Mehta No relevant relationships by Denzil Reid

Phase Ib study of AVB-S6-500 (axl inhibition) in combination with durvalumab (MEDI4736) in patients with platinum-resistant, recurrent epithelial ovarian cancer (NCT04019288) (320)

Objectives: Immune checkpoint blockade (ICB) has demonstrated efficacy in a small fraction of patients with platinum-resistant ovarian cancer (PROC), some with durable responses. The receptor tyrosine kinase AXL and its sole ligand, GAS6, are possible mediators of T cell exclusion and an attractive target due to the expected synergy between AXL inhibition and immune targeting agents. The recommended phase II dose (RP2D), safety, and efficacy of the combination of AXL inhibition via AVB-S6-500 with durvalumab (MEDI4736) were evaluated in patients with PROC. Methods: In this open-label Phase Ib open-label study, patients with PROC received AVB-S6-500 and durvalumab therapy in escalating dosing regimens guided by a Bayesian optimal interval (BOIN) design: durvalumab (1500 mg Q4W) and AVB-S6-500 (10mg/kg Q2W, 15mg/kg Q2W, 20mg/kg Q2W) with durvalumab infused prior to AVB-S6-500. The response was evaluated using modified RECIST v1.1. Pharmacokinetic/pharmacodynamic (PK/PD) studies were collected, and PD-L1 status and tumor/tumor microenvironment AXL and GAS6 staining pre and on-treatment were assessed. Results: Eleven patients with epithelial ovarian cancer (six clear cells [55%], four high-grade serous [36%], one endometrioid histology [1%]) received treatment per protocol. The median number of prior lines of therapy was 3 (range: 1-5);73% (8/11) of patients had received prior bevacizumab. There were no DLTs noted over the 6-week period and no grade ≥3 adverse events attributed to study drugs. Five patients experienced an immune-related AE, most commonly liver enzyme elevations (36%). Infusion reaction with AVB-S6- 500 was noted in the first two subjects, prompting the institution of a premedication regimen, after which only one of the nine additional patients experienced an infusion reaction. Dose delays greater than one week occurred in six (55%) patients;three patients experienced delays for cancer-related complications (small bowel obstruction, pneumonia, severe fatigue), while three patients experienced delays for non-medical causes (COVID/travel, weather). Patients received therapy for a median of two cycles (range: 1-6), and there were no responses noted across all dosing levels. One patient had stable disease, with a duration of response of three months. Only two patients had strong (2+) AXLstaining on pretreatment biopsy, both with high-grade serous histology. The majority of serum AXL levels were within previously demonstrated ranges (range: 5.6-112ng/mL), though two patients had comparatively high levels (102, 112ng/mL). PK/PD analysis revealed expected AVB-S6-500 levels at initial postdose (C1D1), but low levels at trough (C2D1 predose) when compared to prior AVB-S6-500 data [1]. Conclusions: The combination of AVB-S6-500 and durvalumab was tolerable in this PROC patient population at all dosing levels tested. Exploratory studies to correlate lack of response to AXL-GAS6 pathway alterations, tumor microenvironment, and clinical characteristics, such as prior treatment, dosing delays, burden of disease, and ascites, are ongoing.