Hydroxychloroquine pre-exposure prophylaxis provides no protection against COVID-19 among health care workers: a cross-sectional study in a tertiary care hospital in North India

Objectives The use of Hydroxychloroquine (HCQ) prophylaxis has been recommended by the National task force constituted by the Indian Council of Medical Research (ICMR) for the prevention of corona virus disease 2019 (COVID-19) among healthcare workers (HCWs). However, this recommendation was based essentially on the preclinical data and limited clinical experience. The aim of this study was to evaluate the efficacy and safety of HCQ as a pre-exposure prophylaxis for COVID-19 infection among Indian HCWs. Methods A cross-sectional study was conducted among HCWs of a tertiary care hospital in north India. The HCQ prophylaxis was initiated among 996 HCWs and they were followed up to 8 weeks for conversion to COVID-19 positive status and any adverse drug reaction (ADR). Results About 10.3% of the study participants were tested positive for COVID-19 which was comparable to the positivity rate among HCWs not taking HCQ prophylaxis (9.7%). Conclusions HCQ was well tolerated at a weekly dose of 400 mg for 8 weeks but provided no additional benefit in prevention of COVID-19 among HCWs.

Investigation on the Effect of Dose, Frequency and Duration of Allergen Exposure on Development of Staphylococcal Infections in a Chronic Model of Canine Atopic Dermatitis

Canine atopic dermatitis (CAD) is chronic and frequently complicated by Staphylococcal infections. Understanding the role of allergen dose, frequency and duration of exposure in triggering infections requires a model. Most models elicit acute inflammation and do not mimic real-life disease. Here we describe the effects of allergen exposures on development of infections in a model of chronic CAD. Diagnosis of pyoderma was based on clinical signs and consistent cytology. Study 1 evaluated the role of duration of exposure keeping the daily dose constant (25 mg/day). The one-week protocol involved three exposures, 3 days in a row. The one-month protocol involved twice-weekly challenges for 4 weeks. The three-month protocol involved twice-weekly challenges for 12 weeks. Study 2 evaluated different daily doses while keeping constant the total weekly dose (25 mg) and duration (3 weeks). Low-dose used 5 mg/day for 5 days, each week. High-dose used 12.5 mg/day twice-weekly. In Study 1, the longer the exposure, the more dogs developed pyoderma (6/9 in the three-month study, 2/9 in the one-month and 0 in the one-week). In Study 2, low-dose daily exposure caused more infections (5/8) than high-dose infrequent exposure (0/8). It is concluded that low-grade, daily exposure for a long time is most relevant for development of staphylococcal infections.

A multicentre, multi-national, double-blind, randomised, active-controlled, parallel-group clinical study to assess the safety and efficacy of PDA10 (Epoetin-alpha) vs. Eprex® in patients with anaemia of chronic renal failure

Background Erythropoietin stimulating agent (ESA) has been standard of care in treating renal anaemia for the past 20 years. Many patients have limited access to ESA in view of long-term costs leading to suboptimal ESA dosage. Biosimilar epoetin is a potential cost-effective alternative to originator for optimal renal anaemia management. Objective To determine efficacy and safety of PDA10 in treating renal anaemia in haemodialysis patients, in comparison to the originator epoetin-α, Eprex®. Methods A phase 3, multicentre, multi-national, double-blind, randomised, active-controlled and parallel group study conducted over 40 weeks in Malaysia and Korea. End stage kidney disease patients undergoing regular haemodialysis who were on erythropoietin treatment were recruited. The study has 3 phases, which included a 12-week titration phase, followed by 28-week double-blind treatment phase and 24-week open-label extension phase. Results The PDA10 and Eprex® were shown to be therapeutically equivalent (p < 0.0001) with mean absolute change in haemoglobin from baseline of − 0.176 (± 0.91) g/dl and − 0.118 (± 1.114) g/dl, respectively. Weekly dose change was 10.01 IU/kg/week in PDA10 group and 10.30 IU/kg/week in Eprex® group, which has no significant difference. There were no significant differences in the safety profile between PDA10 and Eprex® groups. Conclusion This study has confirmed the therapeutic equivalence between PDA10 and Eprex® in terms of efficacy, dosage requirement and safety profile in haemodialysis patients with renal anaemia. Trial registration The study was registered with the National Medical Research Register (NMRR-13-400-16313). This study has been registered retrospectively with Clinical Research Information Service (CRiS), Republic of Korea on 25 March 2021.

Real-World Effectiveness of Damoctocog Alfa Pegol in the Subgroup of Adolescent Hemophilia A Patients Aged 12-18 Years in the ATHNdataset

Background: The ATHNdataset is a HIPAA-compliant, de-identified database, sponsored by the American Thrombosis and Hemostasis Network. Over 40,000 people with a bleeding or clotting disorder followed at United States hemophilia treatment centers (HTC) have submitted health information, including 15,747 hemophilia A patients. Aims: To evaluate the effectiveness of damoctocog alfa pegol (BAY 94-9027/Jivi®) to treat hemophilia A adolescent patients aged between 12-18 years in a real-world setting. Methods: The ATHNdataset was queried for people with hemophilia A aged ≥12 years of age treated with damoctocog alfa pegol. From this dataset adolescent patients aged between 12-18 years, treated either prophylactically or on-demand were identified. Collected data included baseline demographic data, treatment history, comorbidities and bleeding rates. The data were captured via patient chart review and entered into the database. The database was queried for patient data between January 1, 2010 and October 31, 2020. Results: At the data cutoff, 16 patients aged between 12-18 years were being treated with damoctocog alfa pegol. In this group, 13 patients (81%) had severe hemophilia A and 3 patients (19%) had mild/moderate disease. The majority of patients were male - 14/16 (87.5%) with 2/16 (12.5%) being female and the mean age of patients was 15.9 years old (median = 15.8). Of the total, 4 patients (25%) had a history of inhibitors. Patients had an average of 1.2 years of therapy with damoctocog alfa pegol and most (56%) had over 12 months of treatment. All the patients included in this analysis had documented bleeding rates in the ATHN system (Table 1). Mean total annualized bleed rate (ABR) was 0.05. Mean joint ABR and spontaneous ABR were zero. In the subgroup of patients who were on prophylaxis with damoctocog alfa pegol (n = 13), the mean total ABR, joint ABR and spontaneous ABR were zero. The proportion of patients with zero total bleeds during the entire observational period was 15/16 (94%) in the overall cohort and 13/13 (100%) in adolescent patients who were on prophylaxis. The majority of patients who were on prophylaxis 9/13 (69%) were treated twice-weekly with the mean weekly dose of 77.2 IU/kg/wk. Conclusions: The data from this analysis show that damoctocog alfa pegol provides protection from bleeding events in adolescent patients aged 12-18 years in the real-world setting. Mean ABR was low in this patient population, with 94% of patients experiencing zero bleeds. This data should be interpreted with caution due to limitations in real-world studies. Figure 1 Figure 1. Disclosures Recht: American Thrombosis and Hemostasis Network: Current Employment; Oregon Health & Science University: Current Employment; Foundation for Women and Girls with Blood Disorders, Partners in Bleeding Disorders: Speakers Bureau; uniQure: Consultancy; Takeda: Consultancy; Sanofi: Consultancy; Pfizer: Consultancy; Octapharma: Consultancy; Novo Nordisk: Consultancy; Kedrion: Consultancy; Hema Biologics: Consultancy; Genentech: Consultancy; CSL Behring: Consultancy; Catalyst Biosciences: Consultancy. He: ATHN: Ended employment in the past 24 months. Moulton: Bayer: Current Employment. Charafi: Bayer: Current Employment.

Baseline VWF:Ag Level and Body Mass Index Are Inverse Influencing Factors of Annualized Total Bleeding Rate and Annualized Joint Bleeding Rate Respectively in Severe-Type Adult Patients with Hemophilia a (PwHA) with Episodic Treatment with rFVIII

Introduction: Bleeding phenotypes of severe-type patients with hemophilia A (PwHA) vary greatly, which influence factor consumption and medical cost. Factors affecting bleeding patterns of PwHA include various procoagulant and anticoagulant factors, joint condition and physical activity, etc. We aimed to investigate clinical factors influencing by-nature bleeding frequency of severe-type PwHA during episodic treatment. Methods and materials: There were 19 non-inhibitor, severe-type, previously treated PwHA aged &gt;20 years, who had at least one to five major joints arthropathy, retrospectively enrolled from two hemophilia centers for analysis. They had been refusing prophylaxis therapy with FVIII product due to heavy burden of frequent intravenous FVIII injection and had long-term episodic treatment. Clinical informations were collected from November 2017 to November 2018, including age, body mass index (BMI), body weight, ABO blood grouping, HCV and HIV infection status, baseline VWF:Ag and VWF:activity, mutation of F8 gene. Annualized bleeding rate (ABR) and annualized joint bleeding rate (AJBR), weekly doses and annualized factor consumption costs (calculated by new Taiwan dollars, NTD) were obtained from the patients' medical records. Results: The PwHA with ABR &lt;24 had significantly lower proportion of blood-group-O patients, higher baseline VWF:Ag and VWF:activity than those with ABR &gt;24.(P-value &lt;0.05) The PwHA with AJBR &lt;13 had significantly higher BMI than those with AJBR &gt;13.(P-value &lt;0.05) There was no significant difference in ABR, AJBR, weekly dose, and annualized factor cost between PwHA with O blood group and non-O blood group. Compared with PwHA with baseline VWF:Ag or VWF:activity &lt;145%, those with baseline VWF:Ag or VWF:activity &gt;145% had significantly older age (34.9 vs 53.2 years, P-value &lt;0.05), higher BMI (25.2 vs 29.9, P-value &lt;0.05), lower ABR (58.2 vs 12.2 per year, P-value&lt;0.01), lower AJBR (46.8 vs 10.8 per year, P-value&lt;0.01), lower weekly dose (42.4 vs 10.6 IU/kg/wk, P-value&lt;0.01), and lower annualized factor consumption costs (4,177,732 vs 1,120,704 NTD, P-value&lt;0.01). Compared with PwHA with BMI &lt;28, those with BMI &gt;28 had significantly lower ABR (58.2 vs 12.2 per year, P-value&lt;0.05), lower AJBR (46.8 vs 10.8 per year, P-value&lt;0.05), higher baseline VWF:activity (94.6% vs 190.2%, P-value &lt;0.05), and lower weekly dose (38.5 vs 17.1 IU/kg/wk, P-value &lt;0.05). By backward-stepwise multivariate linear regression, baseline VWF:Ag and BMI were identified as independent and significant inverse influencing factors for ABR and AJBR, respectively.(P-value &lt;0.05) Conclusion: For severe-type adult PwHA with episodic treatment, baseline VWF:Ag or VWF:activity &gt;145% was associated with lower ABR, AJBR, weekly dose, and annualized factor cost. BMI &gt;28 was associated with lower ABR, AJBR, and weekly dose consumption. Baseline VWF:Ag and BMI were revealed as inverse influencing factors for ABR and AJBR, respectively. The results of our study could be useful for clinicians to have an insight into diversity of bleeding phenotypes of by-nature severe-type PwHA. For developing countries where factor concentrate resources are not enough, these clinical influencing factors might be helpful for the management of therapeutic strategies and resource allocation for severe PwHA. Disclosures No relevant conflicts of interest to declare.

DDRE-47. ASSESSMENT OF BRAIN PENETRANCE, BIODISTRIBUTION, AND EFFICACY OF PLATINUM (IV)-CONJUGATED FLUORINATED MACROCYCLIC CELL-PENETRATING PEPTIDES IN A MURINE GLIOBLASTOMA MODEL

INTRODUCTION Glioblastoma (GBM), an aggressive brain tumor with a poor prognosis, presents an average of 2% of patients surviving beyond 2 years after diagnosis. Therapies to effectively manage glioblastoma are hindered due to the presence of the blood-brain barrier (BBB). Previously, a cell-penetrating peptide, M13, was conjugated to a Pt(IV) cisplatin prodrug, via amide bond formation. The conjugated Pt(IV) releases active cisplatin upon intracellular reduction. Herein, we investigated the BBB-penetrance and biodistribution of M13 conjugated to Pt(IV), as well as its effectiveness against GBM in mouse models. METHODS M13 platinum-conjugate tumor cell killing capacity was assessed by luminescent cell viability assays in vitro. By using Inductively-Coupled Plasma Mass-Spectrometry for platinum detection, BBB penetration and bio-distribution studies were performed in a three-dimensional BBB spheroid in vitro model and in vivo in mouse brain, intracranial tumor, and peripheral organs. Dose-regime studies involved observations of symptomatology and weight variations after bi-weekly injections of platinum compounds at 2mg/kg and 5mg/kg. RESULTS The Pt(IV)-M13 conjugate possesses tumor cell killing effects similar to cisplatin when tested in GBM cell lines in vitro. Platinum increased by using Pt(IV)-M13 when compared to cisplatin in our in vitro BBB-spheroid model (20-fold, p-value=0.0033), in brain tissue (10-fold, p&lt; 0.0001) and GBM tumor-bearing mice models (7.5-fold, p&lt; 0.0001). Bio-distribution of platinum delivered by Pt(IV)-M13 in spleen, heart and blood was significantly different to cisplatin 5hrs. after intravenous injection (p&lt; 0.001). Bi-weekly dose regimes of Pt(IV)-M13 are tolerable in nude mice without toxicity at a similar concentration to reported tolerable cisplatin doses at 5 mg/kg. Finally, Pt(IV)-M13 significantly increased survival in a murine glioblastoma xenograft model compared with controls (median 24 days vs. 29 days, p-value=0.0071). CONCLUSION Overall, our data support the further development of BBB-crossing peptide-drug conjugates for GBM treatment.

P024 Efficacy and tolerance of methotrexate in patients with Juvenile Idiopathic Arthritis

Background Juvenile idiopathic arthritis (JIA) is the most common inflammatory rheumatic disease for children. The therapeutic management depends on several factors and is based on different treatments including methotrexate (MTX). The aim of our study was to determine the efficacy and safety of MTX in JIA. Methods This is a monocentric retrospective study of 37 patients followed for JIA according to the 2001 International League of Association of Rheumatology (ILAR) criteria and treated with MTX. Socio-demographic, clinical, paraclinical and therapeutic data were collected. Disease activity was assessed by the JADAS score. Highly active JIA was defined as JADAS superior to 25. Results There were 25 boys (67.5%) and 12 girls (32.4%) with a median age of 6.3 years [4–13]. The average duration of the rheumatic disease was 2.7 years [2.5–5.3]. The type of JIA was: oligoarticular in 22 cases (59.4%), polyarticular in 10 cases (27%), arthritis related to enthesitis in 3 cases (8.1%) and systemic in 2 cases (5.4%). Twenty patients (54%) received oral corticosteroid therapy for a mean period of 1.7 years [0.6–3] with a mean daily dose of 10 mg/day of prednisone or equivalent. Oral MTX was prescribed to all patients with a mean weekly dose of 10 mg/m2 body surface [10–15]. MTX was initiated after a mean period of 6.2 months [3.1–11.4] from diagnosis. The mean treatment duration was 50 months [34–66]. Observance of MTX was 80.5%. Remission with MTX was achieved in 28 patients (75.6%) after a mean treatment duration of 7.5 months [5–11], with a mean JADAS of 5.1 [3.5–10]. Despite good observance of MTX, eight patients (21.6%) continued to have high disease activity with a mean JADAS score of 32 [25–40]. Tolerance to oral MTX was good, with side effects occurring only with 5 patients (13.5%), such as epigastralgia in 2 cases (which disappeared after switching to the intramuscular administration), a skin reaction in one case, and hepatic cytolysis reversible when stopping the treatment in 2 other cases. Conclusion MTX still has a place in the therapeutic management of JIA and appears to be a well-tolerated and effective treatment.

P031 Adherence with Methotrexate in Tunisian Juvenile Idiopathic Arthritis Patients

Background Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in the pediatric population. Methotrexate (MTX) has been considered as the cornerstone of treatment of poly and oligoarticular subtypes of JIA. However, this treatment is supposed to be for long term, which may involve an obstacle for adherence. The aims of the study were to evaluate adherence of Tunisian JIA patients to MTX and to identify factors associated with high adherence to MTX. Methods A cross-sectional study including patients with confirmed JIA diagnosis, according to the International League of Associations for Rheumatology (ILAR) criteria, was performed. Demographic data as well as disease characteristics were obtained from medical records. Laboratory markers including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were collected. Adherence was measured, for patients under MTX for &gt;3 months, using the 5-item Compliance Questionnaire Rheumatology (CQR5) (1). Patients were divided into two groups: group 1: High adherence (HA) for patients having a CQR5 ≥ 80% and group 2: low adherence (LA) for patients having CQR5 &lt; 80%. A p inferior to 0.05 was considered statistically significant. Results The study included 29 patients (10 males and 19 females) with a mean age at disease onset of 9.1 ± 3.4 years. The mean disease duration was 61 ± 79 months [7–336]. JIA subtypes were in decreasing order of frequency as follows: enthesitis-related arthritis (n = 13), oligoarticular (n = 8), Polyarticular without rheumatoid factor (n = 4), Polyarticular with rheumatoid factor (n = 2), systemic (n = 1) and, psoriatic arthritis (n = 1). A biologic inflammatory syndrome was found in 48.3% (n = 14) of cases. The mean ESR and CRP were 20 mm/h ± 11.3 [3–98] and 5 ± 17.8 mg/l [0–56] respectively. Nineteen (65.5%) patients had coxitis. Overall, 55.17% of patients (n = 16) were treated with MTX with a mean weekly dose of 9.2 ± 3.2 mg [5–15]. MTX was orally administrated in all patients. NSAIDs and prednisone were prescribed in 51.7% (n = 15) and 17.2% (n = 5) of cases respectively. The MTX was associated with biological DMARDs in five patients (17.2%). It was about Etanercept in 4 patients and Tocilizumab in 1 patient. Mean CQR5 score was 70.8% ± 18 [25–100]. Only seven patients (43.8%) showed high adherence to MTX. The statistical study revealed no difference between HA and LA in term of gender (P = 0.84), age at disease onset (P = 0.39), disease duration (P = 0.9), prednisone use (P = 0.22), the occurrence of coxitis (P = 0.2), ESR (P = 0.83) and CRP (P = 0.033) rates. Conclusion In this study, less than one half of JIA patients were highly adherent to MTX according to CQR5. Low adherence should be considered before declaring MTX treatment failure.

COST-MINIMIZATION ANALYSIS OF USING SHORT AND LONG-ACTING ERYTHROPOESIS-STIMULATING AGENTS FOR CORRECTION OF NEPHROGENIC ANEMIA AGAINST THE BACKGROUND OF SUBSTITUTION THERAPY

Clinical trials conducted in various countries indicate that the use of epoetin alfa in patients with nephrogenic anemia in chronic kidney disease can increase the effectiveness of treatment, reduce the incidence of cardiovascular and infectious complications, and reduce mortality in patients with chronic kidney disease.The aim of the article was to conduct a comparative clinical and economic assessment of the treatment costs of nephrogenic anemia in adult dialysis patients with recombinant human erythropoietins: epoetin alfa, darbepoetin and long-acting methoxy polyethylene glycol – epoetin beta.Materials and methods. The study took into account direct medical costs of nephrogenic anemia pharmacotherapy on the basis of 1 year maintenance therapy according to the following scheme: epoetin alfa – 3 times per week, darbepoetin alfa – once per week, methoxy polyethylene glycol – epoetin beta – once per 2 or 4 weeks. A “costs minimization” analysis was performed for equivalent maintenance epoetins doses for intravenous and subcutaneous administrations. Epoetin alpha equivalents were calculated for an average patient weighing 75 kg by converting a weekly dose of short-acting epoetin (7500 IU) into equivalent doses using dose conversion factors.Results. In the hypothetical cohort of patients under study, epoetin alfa, darbepoetin alfa, and methoxy polyethylene glycol – epoetin beta not differ in effectiveness in achieving target Hb values and in safety. With the equal effectiveness of the investigated drugs, in the studied patients, intravenous epoetin alfa can be less expensive drug therapy relative to the equivalent doses obtained by the calculation: darbepoetin by 14–24% and methoxy polyethylene glycol – epoetin beta by 4–30%. The change-over of patients to the subcutaneous administration makes it possible to decline a weekly dose of epoetin alfa by 20–30% by reducing the frequency of taking the drug to twice a week, and to reduce the cost of drug therapy by a third.Conclusion. Intravenous and subcutaneous administrations of epoetin alfa 2500 IU may be a more economical drug therapy in comparison with the equivalent doses of darbepoetin and methoxy polyethylene glycol – epoetin beta.

Homeopathy for COVID-19 Prevention: Report of an Intervention at a Brazilian Service Sector Company

Background COVID-19 quickly became a serious public health problem worldwide, with serious economic and social repercussions. Homeopaths around the world have been studying to find a genus epidemicus (GE) medicine that might help in the prevention and treatment of this disease. Objective To compare the incidence of COVID-19 between employees who received or did not receive a homeopathic GE medicine for disease prevention. Methods Retrospective cohort analysis. The study population comprised all employees of a service sector company in São Paulo, Brazil, and followed up by the corporate Occupational Health department. Intervention consisted of administering Arsenicum album 30cH in a one-weekly dose. Primary outcome was incidence of COVID-19 during 3-months' follow-up (April to July, 2020). Results We analyzed 1,642 of 1,703 employees without previous diagnosis of COVID-19 at onset of the study period: 53.34% of employees were referred to telework at home and did not receive intervention (Group 1, G1); 24.66% remained working on-premises in the state of São Paulo and received the intervention (Group 2, G2); 21.98% remained working on company premises in other states and did not receive intervention (Group 3, G3). Incidence rate of COVID-19 was respectively 13.35%, 0.74%, and 67.87% (p < 0.001). The odds ratio of being infected in (1) G3 versus G1 was 13.70 (95% confidence interval [CI], 10.21 to 18.39), (2) G3 versus G2 was 283.02 (95% CI, 88.98 to 900.18), and (3) G1 versus G2 was 20.66 (95% CI, 6.53 to 65.39). Limitations The present is a retrospective analysis of a real-world experience. We could not ensure direct observed treatment, and neither could we control adherence to general prevention measures outside company premises. Conclusion The incidence of COVID-19 was significantly lower amongst on-premises employees who received the GE medication in comparison to workers who did not receive the intervention (those either at other company premises or teleworking at home).