scholarly journals OP0173 IMMUNOMODULATION CO-THERAPY WITH PEGLOTICASE: DATABASE TRENDS 2014-2019

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 108.2-108
Author(s):  
B. Lamoreaux ◽  
M. Francis-Sedlak ◽  
K. Svensson ◽  
R. Holt

Background:Pegloticase is a PEGylated biologic therapy for patients with uncontrolled gout who have not improved on or could not tolerate conventional urate-lowering therapies.1All biologics have the ability to engender anti-drug antibodies (ADAs) and it is known that some patients given pegloticase develop ADAs that cause them to stop treatment prior to recieving a complete course of therapy.2-3In other rheumatic autoimmune diseases, DMARDs such as methotrexate or azathioprine are used as standard of care to prevent the development of ADAs to biologics. These DMARDs often allow patients to remain on biologic therapies longer and recieve the full therapeutic benefits while minimizing adverse events.4While pegloticase has been used traditionally as monotherapy, recent case series have demonstrated the therapeutic benefit of immunomodulator co-administration, allowing more patients to receive a full course of pegloticase therapy.5-6Little has been published on how widespread this practice is and whether it has changed over time.Objectives:To examine medical claims database from 2014-2019 for trends in immunomodulating therapies being co-prescribed with pegloticase.Methods:An IQVIA claims database (November 2014 to October 2019) representing 1.3 billion claims, covering 30 million patients diagnosed with gout or CKD, was utilized to search for patients who had received pegloticase. Patients who had recieved pegloticase were classified as having been on an immunomodulating co-therapy if they were prescribed methotrexate or azathioprine within 60 days before or after initiation of their first pegloticase infusion.Results:We found relatively steady low rates of immunomodulation co-therapy with pegloticase from 2014 through 2018 ranging from 1% in 2016 to 4% in 2018 (Figure 1). In 2019 however, the proportion of pegloticase patients that were co-treated with methotrexate or azathioprine therapy increased to 15%. Most patients were started on immunomodulating therapy 20 days before to 10 days after initiation of pegloticase. Methotrexate was the more frequently used immunomodulaton co-therapy as compared to azathioprine.Conclusion:We found evidence of a relatively dramatic increasing initiation of immunomodulation therapy with pegloticase beginning soon after a November 2018 presentation of a case series which demonstrated improved response rates of pegloticase when co-administered with methotrexate. These data indicate that clinicians began to more frequently employ a strategy of DMARD co-treatment with pegloticase in 2019 to improve response rates to this important gout medicine.References:[1]Sundy JS, et al.JAMA2011;306:711-20.[2]Abeles AM.Arthritis Research & Therapy2014, 16:112[3]Strand V, et al.BioDrugs2017; 31:299–316.[4]Krieckaert CL, et al.Arthritis Res Ther2010;12:217.[5]Botson J and Peterson J.Ann Rheum Dis.2019; 78: A1289.[6]Bessen SY, et al.Semin Arthritis Rheum.2019;49:56-61.Disclosure of Interests:Brian LaMoreaux Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics, Megan Francis-Sedlak Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics, Karl Svensson Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics, Robert Holt Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1252-1252
Author(s):  
Aleksander L. Chojecki ◽  
Justin Arnall ◽  
Danielle Boselli ◽  
Kristyn Y. DiSogra ◽  
Allison Karabinos ◽  
...  

Abstract Introduction: Treatment options for newly diagnosed patients (pts) with acute myeloid leukemia (AML) have historically been limited. The combination of a hypomethylating agent and venetoclax (HMA/Ven) has emerged as standard of care treatment for elderly and/or unfit pts with newly diagnosed AML. Liposomal cytarabine/daunorubicin (CPX-351) has also become standard of care therapy for pts with AML with myelodysplasia related changes or therapy-related AML. Despite being an intensive regimen, CPX-351 may have a more favorable toxicity profile compared to other intensive regimens. As a result, CPX-351 may be offered to older fit pts who may not have been candidates for traditional induction regimens. As the landscape for frontline treatment options evolves, there are now overlapping pt populations who may be eligible for either frontline treatment option. A retrospective study that included clinical trial pts demonstrated similar response rates in pts treated with HMA/Ven and CPX-351 (Asghari Blood 2019). Similarly, a study of secondary AML pts receiving HMA/Ven and CPX-351 showed no difference in remission rate or survival (Salhotra Am J Hematol 2021). There remains a shortage of data describing clinical characteristics of pts selected for and treated with standard-of-care HMA/Ven and CPX-351. We present a study on our center's experience. Methods: The purpose of this study was to evaluate the clinical characteristics and outcomes of adult pts with newly diagnosed AML who were treated with either CPX-351 or HMA/Ven as initial therapy. Consecutive pts treated with either of these two induction therapies between August 2017 and June 2021 were evaluated retrospectively. Pts were eligible for response evaluation if they received at least 3 doses of CPX-351 or 28 days (1 cycle) of venetoclax ("response cohort"). All pts treated with CPX-351 or HMA/Ven were included in survival analysis ("survival cohort"). Response assessment is based on ELN-2017 criteria. Pt characteristics were described and compared using Fisher's Exact tests. Kaplan-Meier methods were used to summarize overall survival, and log-rank tests were used for the comparison of frontline therapies. Cox proportional-hazards regression estimated hazard ratio (HR), 95% confidence interval (CI), and interactions between frontline therapy and age at induction start. Results : A total of 79 pts were identified receiving frontline HMA/Ven or CPX-351; 61 pts (77%) were evaluable for response. Of the response cohort, 21 (34%) were treated with CPX-351 and 40 (66%) with HMA/Ven; pt characteristics are described in Table 1. CPX-351 pts were younger at start of induction (P<0.001); many pts in both treatment groups had unfavorable ELN risk scores at diagnosis (CPX 43%, HMA/Ven 41%; P>0.99). 33% and 23% of the HMA/Ven cohort achieved CR and CRi respectively; in the CPX-351 cohort 57% and 5% achieved CR and CRi respectively. A greater fraction of CPX-351 pts proceeded to allogeneic stem cell transplant than HMA/Ven pts (67% vs 23%; P<0.001). No differences were detected in achievement of MRD negativity by flow cytometry (P=0.51) or molecular profile (P=0.52). Median follow-up for all pts was 18.9 months; 42 deaths occurred. Differences in survival between the frontline therapies were not detected in the survival cohort (HR, 1.31; 95% CI, 0.67 to 2.57; P=0.43) nor the response cohort (HR, 0.97; 95% CI, 0.45 to 2.09; P=0.93); these results were unaffected by adjustments for age at induction, ELN risk score, and transplant status. 8 pts who initially received CPX-351 and had refractory disease later went on to receive HMA/Ven reinduction; 2 achieved CRi, 2 MLFS, 3 Refractory and 1 Death in Aplasia. 1 pt who initially received HMA/Ven with refractory disease went on to receive CPX-351. This pt was refractory to CPX-351. Conclusion: HMA/Ven and CPX-351 are effective frontline treatment options with similar response rates and survival outcomes in newly diagnosed adults with AML. Pts treated with CPX-351 were younger and more likely to proceed with allogeneic transplantation, in line with standard practice. Though there was heterogeneity in pt populations, age did not appear to affect outcomes. As the landscape for standard-of-care upfront treatment for AML continues to evolve, further studies are warranted to determine optimal therapy selection and sequencing. Figure 1 Figure 1. Disclosures Arnall: Novo Nordisk: Speakers Bureau. Symanowski: Carsgen: Consultancy; Immatics: Consultancy, Other: DSMB Member; Eli Lilly: Consultancy, Other: DSMB Member. Avalos: JUNO: Membership on an entity's Board of Directors or advisory committees. Copelan: Amgen: Consultancy. Grunwald: Cardinal Health: Consultancy; Daiichi Sankyo: Consultancy; Astellas: Consultancy; Agios: Consultancy; Janssen: Research Funding; PRIME: Other; Karius: Consultancy; Bristol Myers Squibb: Consultancy; AbbVie: Consultancy; Pfizer: Consultancy; Blueprint Medicines: Consultancy; Gilead: Consultancy; Incyte: Consultancy, Research Funding; Amgen: Consultancy; Med Learning Group: Other; Sierra Oncology: Consultancy; MDEdge: Other; PER: Other; Trovagene: Consultancy; Stemline: Consultancy.


2021 ◽  
Vol 9 ◽  
pp. 2050313X2110136
Author(s):  
Afsaneh Alavi ◽  
Jeannine Archer ◽  
Patricia Coutts

The objective of this case series was to assess the wound healing effectiveness of a collagen matrix wound dressing containing partially denatured collagen, carboxymethyl cellulose, alginate and ethylenediaminetetraacetic acid in chronic lower extremity ulcers. A total of nine patients with refractory lower extremity ulcers were treated with the collagen contact layer in addition to standard of care. Wound healing progress was measured at 2, 4 and 8 weeks. An average decrease in wound size of 73% was achieved across patients at week 8, with complete healing in two patients. The intervention was easy to use and well tolerated by patients. The results of this study, although preliminary, suggest that the advanced collagen matrix dressing represents an effective and safe treatment strategy for healing refractory chronic lower extremity ulcers of varying etiologies. Further investigation is needed to evaluate efficacy in a larger randomized clinical trial with focus on cost-effectiveness and impact on patient’s quality-of-life.


Author(s):  
Raman R S ◽  
Vijaykumar Bhagwan Barge ◽  
Anil Kumar Darivenula ◽  
Himanshu Dandu ◽  
Rakesh R Kartha ◽  
...  

Abstract Background Currently, there is no specific drug for the treatment of COVID-19. Therapeutic benefits of intravenous immunoglobin (IVIG) have been demonstrated in wide range of diseases. The present study is conducted to evaluate the safety and efficacy of IVIG in the treatment of COVID-19 patients with moderate pneumonia. Methods An open-label, multicenter, comparative, randomized study was conducted on COVID-19 patients with moderate pneumonia. 100 eligible patients were randomized in 1:1 ratio either to receive IVIG + standard of care (SOC) or SOC. Results Duration of hospital stay was significantly shorter in IVIG group to that of SOC alone (7.7 Vs. 17.5 days). Duration for normalization of body temperature, oxygen saturation and mechanical ventilation were significantly shorter in IVIG compared to SOC. Percentages of patients on mechanical ventilation in two groups were not significantly different (24% Vs. 38%). Median time to RT-PCR negativity was significantly shorter with IVIG than SOC (7 Vs.18 days). There were only mild to moderate adverse events in both groups except for one patient (2%), who died in SOC. Conclusions IVIG was safe and efficacious as an adjuvant with other antiviral drugs in the treatment of COVID-19. The trial was registered under Clinical Trial Registry, India (CTRI/2020/06/026222).


Life ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 167
Author(s):  
Pasquale Sansone ◽  
Luca Gregorio Giaccari ◽  
Caterina Aurilio ◽  
Francesco Coppolino ◽  
Valentina Esposito ◽  
...  

Background. Guillain-Barré syndrome (GBS) is the most common cause of flaccid paralysis, with about 100,000 people developing the disorder every year worldwide. Recently, the incidence of GBS has increased during the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) epidemics. We reviewed the literature to give a comprehensive overview of the demographic characteristics, clinical features, diagnostic investigations, and outcome of SARS-CoV-2-related GBS patients. Methods. Embase, MEDLINE, Google Scholar, and Cochrane Central Trials Register were systematically searched on 24 September 2020 for studies reporting on GBS secondary to COVID-19. Results. We identified 63 articles; we included 32 studies in our review. A total of 41 GBS cases with a confirmed or probable COVID-19 infection were reported: 26 of them were single case reports and 6 case series. Published studies on SARS-CoV-2-related GBS typically report a classic sensorimotor type of GBS often with a demyelinating electrophysiological subtype. Miller Fisher syndrome was reported in a quarter of the cases. In 78.1% of the cases, the response to immunomodulating therapy is favourable. The disease course is frequently severe and about one-third of the patients with SARS-CoV-2-associated GBS requires mechanical ventilation and Intensive Care Unit (ICU) admission. Rarely the outcome is poor or even fatal (10.8% of the cases). Conclusion. Clinical presentation, course, response to treatment, and outcome are similar in SARS-CoV-2-associated GBS and GBS due to other triggers.


2021 ◽  
Vol 49 (4) ◽  
pp. 030006052110123
Author(s):  
Sergej M. Ostojic ◽  
Aleksandra Milovancev ◽  
Patrik Drid ◽  
Alexandros Nikolaidis

In this open-label case series trial, we evaluated the effects of a nitrate-based nutritional formula on oxygen saturation (SpO2) and patient-reported outcomes in individuals with coronavirus disease 2019 (COVID-19). Five adult patients (three men and two women, age 39.6 ± 6.9 years) with a positive COVID-19 test result, breathing difficulties, and SpO2 ≤95%, who were free from other pulmonary and cardiovascular conditions, were recruited for this study. Participants were assigned to receive a multi-component nutritional formula (containing 1200 mg of potassium nitrate, 200 mg of magnesium, 50 mg of zinc, and 1000 mg of citric acid) every 4 hours during the 48-hour monitoring period. In all participants, SpO2 improved immediately after administration of the nutritional formula, from 1 to 7 percentage points (mean increase 3.6 ± 2.7 points; 95% confidence interval 0.3 to 7.0). SpO2 remained above baseline values throughout the monitoring interval, with values persisting over threshold values (>92%) for all patients and at each time point during the 48 hours. No patients reported any side effects of the intervention. These promising and rather unexpected results call for immediate, well-sampled, mechanistic randomized controlled trials to validate our findings.


2021 ◽  
Vol 9 (7_suppl3) ◽  
pp. 2325967121S0008
Author(s):  
Sahej S Randhawa ◽  
Emily P Tran ◽  
Nicole A Segovia ◽  
Theodore J Ganley ◽  
Marc Tompkins ◽  
...  

Background: Discoid meniscus epidemiology remains poorly defined for race and sex, in part, due to limitations of retrospective studies and small case series. A better understanding of epidemiology may improve clinical care and diagnostic precision. Purpose: Our purpose is to better define the epidemiology of discoid meniscus by analyzing a large, national database for incidence rates by sex and race. Methods: Analysis was conducted on the national-scale Clinformatics Data Mart Database by Optum. Proportions of the database’s racial categories (Asian, Black, Hispanic, White, and Unknown) in the total population of diagnosed discoid meniscus cases (n = 1,006) were calculated and compared via chi-squared tests to the total database population (n = 65,759,970). This analysis was repeated for the population of patients who received knee arthroscopies (81,205). Incidence rates were calculated from these populations as well. Finally, a multivariable logistic regression analysis based on the population of arthroscopy-receiving patients was performed to control for age, reported gender, and income. Results: Proportions of Asian, Black, Hispanic, and White racial categories in the discoid meniscus group were 5.7%, 7.3%, 20.6%, 66.4%, respectively; the proportions of each racial category in the total population were 5.2%, 10.3%, 13.5%, 71.0%, respectively. Incidence rates (per 10,000) for these groups in the arthroscopy population were 72.9, 25.6, 49.2, 25.6, respectively. Our logistic regression model indicated that race was not a statistically significant predictor for our dataset after income adjusting. Adjusting for other covariates, the odds of a discoid meniscus diagnosis decreased by 6% for each increase in age (p < 0.001) and were 41% lower for males compared to females (p < 0.001). Conclusion: Prior studies have suggested that race (Asian and Hispanic, is a predictor of higher incidence of discoid meniscus – this study did not show a difference in incidence based upon race. Patient sex and age was identified as significant predictors for discoid meniscus, and increasing age showed a decreasing incidence of this condition. This study’s analysis of a large, national claims database allows for a comprehensive epidemiological study on this topic, offering proportions and incidence rates by race appropriate for application to the US population. Its conclusions promote patient sex and age as significant predictors and question the beliefs on race-associated incidence often based on comparing results from the corpus of single-site cohort studies. Tables/Figures: [Table: see text]


2015 ◽  
Vol 4 (3-4) ◽  
pp. 75-82 ◽  
Author(s):  
Hesham Masoud ◽  
Thanh N. Nguyen ◽  
Coleman O. Martin ◽  
William E. Holloway ◽  
Sudheer Ambekar ◽  
...  

Mechanical thrombectomy using retrievable stents or stent retriever devices has become the mainstay of intra-arterial therapy for acute ischemic stroke. The recent publication of a series of positive trials supporting intra-arterial therapy as standard of care for the treatment of large vessel occlusion will likely further increase stent retriever use. Rarely, premature stent detachment during thrombectomy may be encountered. In our multicenter case series, we found a rate of detachment of less than 1% (n = 7/1,067), and all were first-generation Solitaire FR devices. A review of the US Food and Drug Administration database of device experience yielded 90 individual adverse reports of detachment. There were 82, 1 and 7 detachments of Solitaire FR (first generation), Solitaire FR2 (second generation) and Trevo devices, respectively. We conclude with a brief overview of the technical and procedural considerations which may be helpful in avoiding this rare complication.


2014 ◽  
Vol 13 (3) ◽  
pp. 142-145 ◽  
Author(s):  
Elliot Benjamin

Purpose – The purpose of this paper is to describe the therapeutic benefits of a community-based creative artists support group. The author is also the participant/facilitator of the group, which has been ongoing for the past eight months. The relevant experiences of three participants in the group have been chosen, to briefly illustrate the diverse kinds of social and therapeutic value that people with creative artistic inclinations may benefit from. Design/methodology/approach – The philosophy of the author's facilitation of this creative artist support group is based upon the humanistic psychology foundations of Carl Rogers and Abraham Maslow, as well as the author's previous work on the relationship of the creative artist to mental disturbance and mental health. Findings – The pragmatic illustrations of therapeutic benefit from participation in this creative artist support group are directly related to the humanistic supportive atmosphere that is described in this paper as a cornerstone of the Artistic Theory of Psychology. Originality/value – This paper is highly original in the context of the author's description of his Artistic Theory of Psychology, which utilizes the foundation for the “successful creative artist” as being successful in both one's chosen artistic realm as well as making a satisfactory adjustment to day-to-day life. It should also be noted that this paper has been written in the context of a “brief case study” as discussed in August 2013 with the Journal of Public Mental Health editor.


1997 ◽  
Vol 78 (2) ◽  
pp. 920-938 ◽  
Author(s):  
Christopher B. Halsell ◽  
Susan P. Travers

Halsell, Christopher B. and Susan P. Travers. Anterior and posterior oral cavity responsive neurons are differentially distributed among parabrachial subnuclei in rat. J. Neurophysiol. 78: 920–938, 1997. The responses of single parabrachial nucleus (PBN) neurons were recorded extracellularly to characterize their sensitivity to stimulation of individual gustatory receptor subpopulations (G neurons, n = 75) or mechanical stimulation of defined oral regions (M neurons, n = 54) then localized to morphologically defined PBN subdivisions. Convergence from separate oral regions onto single neurons occurred frequently for both G and M neurons, but converging influences were more potent when they arose from nearby locations confined to the anterior (AO) or posterior oral cavity (PO). A greater number of G neurons responded optimally to stimulation of AO than to PO receptor subpopulations, and these AO-best G neurons had higher spontaneous and evoked response rates but were less likely to receive convergent input than PO-best G neurons. In contrast, proportions, response rates, and convergence patterns of AO- and PO-best M neurons were more comparable. The differential sensitivity of taste receptor subpopulations was reflected in PBN responses. AO stimulation with NaCl elicited larger responses than PO stimulation; the converse was true for QHCl stimulation. Within the AO, NaCl elicited a larger response when applied to the anterior tongue than to the nasoincisor duct. Hierarchical cluster analysis of chemosensitive response profiles suggested two groups of PBN G neurons. One group was composed of neurons optimally responsive to NaCl (N cluster); the other to HCl (H cluster). Most N- and H-cluster neurons were AO-best. Although they were more heterogenous, all but one of the remaining G neurons were unique in responding best or second-best to quinine and so were designated as quinine sensitive (Q+). Twice as many Q+ neurons were PO- compared with AO-best. M neurons were scattered across PBN subdivisions, but G neurons were concentrated in two pairs of subdivisions. The central medial and ventral lateral subdivisions contained both G and M neurons but were dominated by AO-best N-cluster G neurons. The distribution of G neurons in these subdivisions appeared similar to distributions in most previous studies of PBN gustatory neurons. In contrast to earlier studies, however, the external medial and external lateral-inner subdivisions also contained G neurons, intermingled with a comparable population of M neurons. Unlike cells in the central medial and ventral lateral subnuclei, nearly every neuron in the external subnuclei was PO best, and only one was an N-cluster cell. In conclusion, the present study supports a functional distinction between sensory input from the AO and PO at the pontine level, which may represent an organizing principle throughout the gustatory neuraxis. Furthermore, two morphologically distinct pontine regions containing orosensory neurons are described.


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