Diacerein Versus Chondroitin Sulfate in Treatment of Adult Kashin-Beck Disease: An Intervention Trial in Heilongjiang Province, China

Background: Kashin-Beck disease (KBD) is a special type of osteoarthritis and has disabled and stunted the growth of hundreds of people in China. It also can affect patients' ability to work and live. So, how to conduct effective treatment for adult KBD patients has become a major public health problem in current KBD endemic areas. In this trial, therapeutic effects of diacerein and chondroitin sulfate on adult KBD was to evaluate and compare so that we can screen out more suitable drug. Methods: 308 KBD patients were divided into two groups and received chondroitin sulphate (Group A) and diacerein (Group B) for 24 weeks, respectively. Data were collected at 0 week (baseline), 12 weeks (primary end point) and 24 weeks (secondary end point) to calculate the proportion of patients with effective therapeutic effect and overall improvement rate (primary efficacy parameters), WOMAC pain and stiffness scores (secondary efficacy parameters). Blood sample was collected to measure liver and renal function indexes. All indexes and parameters were analysed with SPSS software and intent-to-treat (ITT) analysis was applied. Results: Two primary efficacy parameters in group B at primary end point were significantly higher than those in group A (P=0.021, P=0.007), but no statistical differences were seen in these two primary efficacy parameters between two groups at secondary end point or between primary and secondary end points in same group (all P>0.05). In both groups, with the prolongation of treatment time, WOMAC pain and stiffness scores decreased significantly (all P<0.001), but no significant differences were seen between primary and secondary end points (all P>0.05). In addition, in both groups, the occurrences of total adverse events were relatively low and no side effect on liver function was seen. Diacerein also had no side effect on renal function. Conclusion: For treatment of adult KBD, both diacerein and chondroitin sulfate were effective, and diacerein might work stronger than chondroitin sulfate. Taking into account both efficacy and safety, the optimal intervention time of diacerein was 12 weeks. Trial registration: The trial was registered complementally on 31/10/2020, and the registration number in the Chinese Clinical Trial Registry is ChiCTR2000039600 (http://www.chictr.org.cn).

Comparison of biosimilar Tigerase and Pulmozyme in long-term symptomatic therapy of patients with cystic fibrosis and severe pulmonary impairment (subgroup analysis of a Phase III randomized open-label clinical trial (NCT04468100))

Background Patients with cystic fibrosis (CF) need costly medical care and adequate therapy with expensive medicinal products. Tigerase® is the first biosimilar of dornase alfa, developed by the lead Russian biotechnology company GENERIUM. The aim of the manuscript to present post hoc sub-analysis of patients’ data with cystic fibrosis and severe pulmonary impairment of a larger comparative study (phase III open label, prospective, multi-centre, randomized study (NCT04468100)) of a generic version of recombinant human DNase Tigerase® to the only comparable drug, Pulmozyme® Methods In the analyses included subgroup of 46 severe pulmonary impairment patients with baseline FEV1 level 40–60% of predicted (23 patients in each treatment group) out of 100 patients registered in the study phase III open label, prospective, multi-center, randomized study (NCT04468100), and compared efficacy endpoints (FEV1, FVC, number and time of exacerbations, body weight, St.George’s Respiratory Questionnaire) as well as safety parameters (AEs, SAEs, anti-drug antibody) within 24 treatment weeks. Results All outcomes were comparable among the studied groups. In the efficacy dataset, the similar mean FEV1 and mean FVC changes for 24 weeks of both treatment groups were observed. The groups were also comparable in safety, all the secondary efficacy parameters and immunogenicity. Conclusions The findings from this study support the clinical Tigerase® biosimilarity to Pulmozyme® administered in CF patients with severe impairment of pulmonary function.

Trans Sodium Crocetinate (TSC) to Improve Oxygenation in COVID-19

Background: Trans Sodium Crocetinate (TSC) is a bipolar synthetic carotenoid under development as a drug to enhance oxygenation to hypoxic tissue in addition to standard of care. TSC acts via a novel mechanism of action, improving the diffusivity of oxygen in blood plasma. Thus, it is based on physical-chemical principles, unlike most drugs which are based on biochemistry-based mechanisms. We explored the use of escalating doses and multiple daily dosing of TSC as a potential therapeutic for patients suffering from hypoxemia due to SARS-CoV-2 infection. Methods: Individuals ≥18 years who were hospitalized with confirmed SARS-CoV-2 infection and hypoxemia, defined as SpO2 < 94% on room air or requiring supplemental oxygen, WHO ordinal scale 3 through 7 (exclusive of Extra Corporeal Membrane Oxygenation [ECMO]) were enrolled in cohorts of six subjects, each of whom received the same dose (0.25, 0.5, 1.0, or 1.5 mg/kg) of TSC via intravenous bolus every 6 hours in addition to standard of care (SOC). This report describes the safety and efficacy results from the lead-in phase of the study and the population pharmacokinetics (PK) analyses. Safety was assessed as the number of serious adverse events and dose-limiting toxicities (DLTs) observed with each dose. Several efficacy parameters were examined in the lead-in phase and descriptive statistics of efficacy parameters are provided. No formal statistical analyses were performed. The population PK analyses were based on previous analyses and examination of the concentration profiles, and two-compartment linear pharmacokinetic models were evaluated and validated. Covariates, including body size, age, sex, organ function, and dose level, were evaluated for inclusion into the model. Results: TSC was well tolerated. There were no treatment emergent adverse events (TEAEs) reported. There were 2 serious adverse events (SAEs) reported during the study, neither were considered treatment-related. A total of 24 (96%) subjects survived. One subject (4.0%) died during the study as a result of an SAE (respiratory failure), and that event was determined to be due to COVID-19 complications and not related to study drug. There was an observed reduction in the time to improvement in WHO Ordinal Scale with increasing dose. The median time to 1-point reduction in subjects receiving 0.25 mg/kg was 11.5 days versus 7.5 days in the 1.5 mg/kg treatment cohort. The overall range across all doses was 1 day to 28 days. A total of 36.0% of subjects had a 1-point improvement in WHO Ordinal Scale to Day 7. The 1.5 mg/kg dose resulted in observed superior outcomes for multiple secondary clinical outcomes: time to 1-point WHO Ordinal Score improvement through Day 29/discharge, 1-point improvement by Day 7, days to return to room air, and hospital length of stay. The PK results showed that the two-compartment model fit the data well. Clearance decreased with increasing dose level and there was no evidence that clearance was affected by covariates other than dose level. Conclusions: These findings suggest that TSC administration every 6 hours at doses up to 1.5 mg/kg for up to 15 days is safe and well tolerated with predictable pharmacokinetics and demonstrated an observed clinical benefit in the treatment of COVID-19-related hypoxemia.

A comparison of oral versus topical combination of glucosamine sulphate and diacerein in patients of grade 2 osteoarthritis

<p class="abstract"><strong>Background:</strong> The study aimed to compare oral versus topical combination of glucosamine sulphate and diacerein in patients of grade 2 Osteoarthritis.</p><p class="abstract"><strong>Methods: </strong>This was a prospective study of 70 patients with grade 2 osteoarthritis knee, randomly divided into 2 groups of 35 each. The first group was given oral 1500mg of glucosamine and 100mg of diacerein per day and second group was given topical preparation of 10% w/w glucosamine sulphate and 1% w/w diacerein to be applied twice. Both the groups were followed up at 1, 3, 6 and 12 weeks. At each follow up, Visual Analog Scale (VAS) and Lequesne et al scores were used as efficacy parameters. C-Reactive Protein (CRP) level was measured in the beginning and at the end of 12 weeks.</p><p class="abstract"><strong>Results:</strong> Both the groups showed improvement in pain and joint function as depicted by VAS score and Lequesne index however the difference was not statistically significant. The decrease in CRP value was significant in oral group (p value&lt;0.001) but not in topical group (p value of 0.047). Paracetamol demand was slightly higher in topical group however the difference was not significant.</p><p class="abstract"><strong>Conclusions:</strong> Glucosamine sulphate and diacerein combination are effective in improving pain, stiffness and function in patients of grade 2 osteoarthritis knee. However, the efficacy of glucosamine sulphate and diacerein combination- oral as well as topical, in improving pain and stiffness is similar- there is no superiority of one over the other.</p>

Randomized multicenter noninferiority phase III clinical trial of the first biosimilar of eculizumab

Currently, eculizumab is the main effective treatment for paroxysmal nocturnal hemoglobinuria (PNH). The aim of this randomized multicenter noninferiority study was to evaluate the efficacy and safety of the Biosimilar (Elizaria) in comparison with the Originator (Soliris) in patients with PNH. Biosimilar and Originator were administered at a dose of 600 mg weekly for 4 weeks at the initial stage in naive patients, as well as for maintenance therapy at a dose of 900 mg every 2 weeks in all patients. The primary endpoint was a comparative assessment of hemolytic activity based on the area under the lactate dehydrogenase (LDH) concentration–time curve during the maintenance therapy. Thirty-two (32) patients were randomized for therapy with Biosimilar (n = 16) or Originator (n = 16). The mean values of LDH concentration–time curve were similar in both treatment groups without statistically significant differences (p > 0.05). Evaluation of secondary endpoints has shown no statistically significant differences between the groups. Safety values were comparable in both treatment groups. The data obtained confirm that the Biosimilar is not inferior to the Originator in terms of the main efficacy parameter, and is also comparable with it in terms of safety and additional efficacy parameters. Clinicaltrials.gov identifier: NCT04463056

Kontaktkutatás, vezetői információs rendszer

Összefoglaló. Tanulmányunkban bemutatjuk a hazai COVID-járvány első hulláma során kidolgozott informatikai megoldást, amely a kontaktkutatást hálózattudományi megközelítés alapján segítette, és hozzájárult az első hullám sikeres megfékezéséhez. A kifejlesztett vizuális reprezentációs technika látványos és részletekbe menő megértést, problémafeltárást képes biztosítani a járványügyi szakemberek számára. A grafikus elemek segítenek a gyors megértésben, a különböző hálózati elrendezések bizonyos jelenségekre, például gócpontokra, fertőzési klikkekre vagy a földrajzi terjedésre irányíthatják a figyelmet. A böngészőből történő futtatás alacsony technológiai belépési küszöböt biztosít a társterületeken kutatók számára, nekik így nem szükséges a problémafeltáráshoz külön szoftvereket telepíteni. Az adatbázis SQL-alapú szűrése a vizualizációs felületről lehetőséget biztosít összetettebb kérdések megfogalmazására is. Summary. In our study, we present an IT solution developed during the first wave of the domestic COVID epidemic. This tool served as an aid for contact tracing. The development focused on the network scientific aspects and contributed to the successful handling of the first wave. In case of absence of effective drugs or vaccines, controlling a contagious disease can only be achieved by preventing its spread. To this end infectious individuals must be identified, patients, exposed to the infection must be identified, the epidemic branching points that cause the greatest infection must be uncovered, information on the course of the disease must be collected, temporal and efficacy parameters must be determined, and potential cases of infection must be described. One possible way to accomplish these tasks is achieved by contact tracing. Classical contact tracing is carried out by personal data collection, during which the commissioned epidemiologist has to fill in a questionnaire. The questionnaire basically includes data used to identify the infected person, as well as the data of the persons who were in contact with the infected person, i.e. in contact with them. The effectiveness of the research is also enhanced if the questionnaire records disease-related parameters (e.g., symptoms, timing-related times, etc.) as well. Once the disease is known, questionnaires can be designed according to a definite template format, the organization of data collection groups and the associated costs can be planned in advance. However, in the case of a new, unknown disease, flexibility and the ability to adapt quickly during data collection are of paramount importance. The developed visual representation technique is able to provide spectacular and detailed understanding and a problem-solving user interface for epidemiologists. Graphical elements help in quick understanding, different network layouts can direct the attention to certain phenomena such as focal points, infectious cliques, or geographical spreading patterns. Running from a browser provides a low technology entry threshold for researchers in other scientific fields, so they don’t need to install separate software. The SQL-based filtering of the database on the visualization interface also provides an opportunity to study more complex questions. Thus, with the help of the presented computer system, a relational database can be generated from the initially unstructured data of the contact research protocols through several steps. The relational database is made available to analysts and decision-makers. As the final balance of the first wave of COVID-19 in Hungary showed, data from well-organized contact research and processed in appropriate analytical tools can provide important information for controlling the epidemic and saving lives.

AB0466 RETENTION RATE AND EFFECTIVENESS OF SECUKINUMAB VERSUS TNF INHIBITOR SWITCHING IN ANKYLOSING SPONDYLITIS PATIENTS WITH A HISTORY OF TNF INHIBITOR TREATMENT: DATA FROM A KOREAN NATIONWIDE REGISTRY

Background:The choice of second-line biologics for ankylosing spondylitis (AS) patients previously treated with a tumour necrosis factor inhibitor (TNFi) remains unclearObjectives:Here, we compared drug retention and clinical efficacy between AS patients who switched biologics to secukinumab and those who switched to a different TNFi.Methods:AS patients enrolled in the Korean College of Rheumatology BIOlogics registry were included. Patients with previous TNFi exposure were divided into the secukinumab group and the TNFi switching group. Drug retention and clinical efficacy (BASDAI50, ASAS20, ASAS40, ASDAS <2.1, ASDAS clinically important improvement, and ASDAS major improvement) were assessed at the 1 year follow-up. Propensity score (PS)-matched and covariate-adjusted logistic regression analyses were performed.Results:246 had available 1 year follow-up data. Secukinumab as third- or later-line biologics was more frequent than alternative TNFi (54% vs. 14%). PS-matched and multiple covariate-adjusted analyses showed that the odds ratio (OR) for drug discontinuation was comparable between the secukinumab and TNFi switching groups (OR=1.136; 95% CI, 0.843–1.531 and OR=1.000; 95% CI, 0.433–2.308, respectively). The proportion of patients who achieved BASDAI50 was also comparable between the two groups (OR=0.833; 95% CI, 0.481–1.441 in PS-matched analysis). Other clinical efficacy parameters were also comparable. In the subgroup analysis of AS patients with previous TNFi discontinuation due to ineffectiveness, all clinical efficacy parameters were comparable between the two groups.Conclusion:In AS patients with previous exposure to a TNFi, switching biologics to secukinumab and switching to an alternative TNFi resulted in comparable drug retention and clinical efficacy.References:[1]Micheroli R, Tellenbach C, Scherer A, et al. Effectiveness of secukinumab versus an alternative TNF inhibitor in patients with axial spondyloarthritis previously exposed to TNF inhibitors in the Swiss Clinical Quality Management cohort. Ann Rheum Dis 2020;79:1203-9.Disclosure of Interests:None declared.