scholarly journals Glucocorticoid maintenance therapy and severe infectious complications in ANCA-associated vasculitis: a retrospective analysis

2020 ◽  
Author(s):  
Claudius Speer ◽  
Christine Altenmüller-Walther ◽  
Jan Splitthoff ◽  
Christian Nusshag ◽  
Florian Kälble ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Kidney Function ◽  
Patient Survival ◽  
Disease Onset ◽  
Infectious Complications ◽  
Physical Damage ◽  
Anca Associated Vasculitis ◽  
Time To Relapse ◽  
The Impact ◽  
Patient Survival Time

AbstractTo study the impact of glucocorticoid maintenance dose and treatment duration on outcomes in patients with AAV (ANCA-associated vasculitis) with emphasis on infectious complications. A total of 130 AAV patients from two German vasculitis centers diagnosed between August 2004 and January 2019 treated with cyclophosphamide and glucocorticoids for induction therapy and glucocorticoids for maintenance therapy were retrospectively enrolled. We investigated the influence of glucocorticoid maintenance therapy on patient survival, time to relapse, kidney function, infectious complications and irreversible physical damage. The patients were divided into the following groups: patients treated according to the predefined reduction scheme (< 7.5 mg) or patients treated with glucocorticoids ≥ 7.5 mg after 6 months. Compared to patients receiving < 7.5 mg glucocorticoids after 6 months, patients receiving $$\ge $$ ≥ 7.5 mg had an increased rate of infectious episodes per patient (1.7 vs. 0.6; p < 0.001), including urinary tract infection (p = 0.007), pneumonia (p = 0.003), opportunistic pneumonia (p = 0.022) and sepsis (p = 0.008). Especially pneumonia during the first 24 months after disease onset [hazard ratio, 3.0 (95% CI 1.5 − 6.1)] led to more deaths from infection (p = 0.034). Glucocorticoid maintenance therapy after 6 months had no impact on relapse rate or patient survival and decline in kidney function was comparable. Glucocorticoid maintenance therapy with $$\ge $$ ≥ 7.5 mg after 6 months is associated with more severe infectious complications leading to an increased frequency of deaths from infection. Glucocorticoid maintenance therapy has no effect on time to relapse or patient survival and should therefore be critically revised throughout the aftercare of AAV patients.

MO303URINARY ALBUMIN-TO-CREATININE RATIO INDICATES NECROTIZING AND CRESCENTIC GLOMERULONEPHRITIS IN ANCA-ASSOCIATED VASCULITIS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Samy Hakroush ◽  
Björn Tampe
Keyword(s):  
Kidney Function ◽  
Renal Involvement ◽  
Disease Onset ◽  
Clinical Importance ◽  
Kidney Injury ◽  
Histopathological Diagnosis ◽  
Intermediate Risk ◽  
Creatinine Ratio ◽  
Anca Associated Vasculitis ◽  
Renal Biopsies

Abstract Background and Aims Renal involvement is a common and severe complication of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) as it can cause acute kidney injury (AKI), end-stage renal disease (ESRD) or death. We have previously reported that elevated urinary albumin-to-creatinine ratio (uACR) correlates with rapid deterioration of kidney function in ANCA GN. Therefore, we here aimed to describe the association between proteinuric findings and histopathological diagnosis of necrotizing and crescentic ANCA GN in 50 urinary samples at admission and corresponding renal biopsies of patients with AAV. Method A total number of 50 urinary samples at admission and corresponding renal biopsies with confirmed renal involvement of AAV were retrospectively included between 2015 till 2020 in a single-center observational study. Results Renal involvement of AAV revealed variable proteinuria ranging from low-range to nephrotic syndromes, however most patients presented with subnephrotic proteinuria predominated by albumin (uACR). Severely increased uACR levels &gt;300 mg/g correlated with reduction of normal glomeruli (P&lt;0.001), attributed to increased glomerular crescents (P&lt;0.001) and necrosis (P=0.008). By contrast, no such association was observed for global sclerotic glomeruli (P=0.58), revealing that uACR reflects necrotizing and crescentic ANCA GN rather than adaptive glomerular hyperfilitration in chronic sclerosing stage. These findings were additionnaly bolstered by histopathological subgrouping and ARRS: patients with uACR levels &gt;300 mg/g were classified either into Berden’s crescentic class (P=0.002) or ANCA renal risk score (ARRS) high/intermediate risk (P=0.003). No association between uACR levels and extrarenal manifestation of AAV disease could be observered, suggesting that uACR levels reflected specific renal involvement with ANCA GN and further confirmed by survival analysis for cumulative incidence of RRT during the short-term course of disease. In summary, uACR measurements at admission were associated with renal biopsy findings thereafter. Levels of uACR &gt;300 mg/g were more frequently observed in necrotizing and crescentic ANCA GN with classification either into Berden’s crescentic class or ARRS high/intermediate risk and specific for renal involvement in AAV. Conclusion Early identification of patients who mostly benefit from aggressive immunosuppressive therapy is of clinical importance. Our observation that uACR levels at disease onset predict necrotizing and crescentic ANCA GN requires further investigation for therapeutic decision especially in patients with severe deterioration of kidney function.

scholarly journals Indirect Treatment Comparison of CC-486 Versus Azacitidine (AZA) As Maintenance Therapy for Acute Myeloid Leukemia (AML)

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 38-39
Author(s):  
Ashley Tabah ◽  
David Huggar ◽  
Si-Tien Wang ◽  
Scott J. Johnson ◽  
Ronda Copher ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Maintenance Therapy ◽  
Treatment Effect ◽  
Research Funding ◽  
Publicly Traded ◽  
Prognostic Variables ◽  
Hematopoietic Stem ◽  
Treatment Comparison ◽  
Time To Relapse ◽  
The Impact

Introduction: For medically fit patients with AML, intensive chemotherapy (IC) is used to induce complete remission (CR). Following CR, some patients may be considered for curative-intent hematopoietic stem cell transplantation. For others, the aim of treatment is to prevent relapse, which usually occurs within 1 year from CR. Post CR, treatment may include consolidation therapy, consisting of chemotherapy given soon after CR is achieved. In addition, maintenance therapy with intravenous (IV) or subcutaneous (SC) injection of AZA has shown evidence of statistically significant improvement in unadjusted time to relapse, though not in unadjusted overall survival (OS), vs placebo (PBO) in randomized controlled trials (RCTs) (Wei. 2019). In the QUAZAR AML-001 trial, maintenance with CC-486, an oral hypomethylating agent, resulted in significant improvements in unadjusted time to relapse and OS vs PBO (Wei et al. 2019). No head-to-head trials have compared CC-486 with AZA. Objective: To assess the relative efficacy of CC-486 compared with AZA. Methods: A systematic literature review was conducted to identify RCTs assessing AML maintenance therapy with AZA, for comparison with CC-486. Bayesian network meta-analysis (NMA) compared endpoints of CC-486 and AZA. Hazard ratios (HR), 95% credible intervals (CrI), and surface under the cumulative ranking curve (SUCRA) values were calculated. The impact of differences in potential treatment-effect-modifying characteristics between populations in the NMA was explored using anchored matching-adjusted indirect comparison (MAIC). The NMA was repeated using CC-486 vs PBO efficacy from the MAIC, to satisfy the assumption of clinical similarity necessary in NMA (Hoaglin et al. 2011). Results: Four RCTs evaluating OS outcomes that could be compared were identified: QUAZAR AML-001 (CC-486) (Wei et al. 2019), HOVON 97 AML (SC AZA) (Huls et al. 2019), UK NCRI AML16 (SC AZA) (Burnett et al. 2015), and QoLESS-AZA-MLE (SC and IV AZA, included in sensitivity analysis) (Oliva et al. 2019). Other efficacy and safety endpoints were not analyzed owing to lack of comparable data among the 4 identified RCTs. Results of the NMA indicated CC-486 was associated with statistically significant improvement in OS vs SC AZA (HR 0.744; CrI 0.557, 0.998); SC AZA was not statistically different from PBO (HR 0.926; CrI 0.771, 1.120). SUCRA values associated CC-486 with the best OS (98.8%). In a sensitivity analysis, CC-486 was associated with statistically significant improvement in OS vs SC or IV AZA (HR 0.741; CrI 0.556, 0.992). In the MAIC, a structured process was used to evaluate the need for adjustment due to differences in trial populations in the NMA. Populations for each trial were compared (Table). Per methodological guidance (Phillippo et al. 2016), the MAIC sought to adjust characteristics with evidence of (a) treatment-effect-modifying status on the scale of parameters entering the NMA and (b) substantial imbalance across populations. Using the QUAZAR individual patient data, univariate analyses were conducted to determine prognostic and effect-modifying status of variables (Table). For each SC AZA trial, a multivariate Cox model was estimated, including all significant prognostic variables reported, and effect modifiers that remained significant when controlling for prognostic variables and improved model fit. Among variables reported for UK NCRI, no effect modifiers enhanced the multivariate model; for HOVON, treatment interactions with age &gt; 81 years (the oldest age in HOVON) and absolute neutrophil count (ANC) did. MAIC was therefore conducted by re-weighting QUAZAR patients to match means/shares of the HOVON patients, adjusting for mean age, % aged &gt; 81 years, % poor cytogenetic risk, and mean ANC. Effective sample size was 411 (−13% vs N = 472 in QUAZAR). Frequency-weighted, unadjusted (including only a treatment covariate) Cox regression was conducted. After adjusting for effect-modifying differences, the OS improvement of CC-486 vs PBO observed in QUAZAR was maintained in the HOVON population. Incorporating the adjusted HR from the MAIC in the NMA, CC-486 continued to be associated with statistically significant improvement in OS vs SC AZA (HR 0.753; CrI 0.563, 0.998). Conclusion: Maintenance CC-486 appears to significantly improve OS compared with SC AZA for patients with AML who have achieved CR after IC, based on a systematic analysis of RCT outcomes. Disclosures Tabah: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Huggar:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company; Karyopharm Therapeutics: Current equity holder in publicly-traded company; FibroGen: Current equity holder in publicly-traded company. Wang:Medicus Economics: Current Employment; Bristol Myers Squibb: Research Funding. Johnson:Medicus Economics: Current Employment; BMS: Research Funding. Copher:Bristol Myers Squibb: Current Employment. O'Connell:Bristol-Myers Squibb: Consultancy; Other biopharmaceutical manufacturers: Consultancy; Medicus Economics, LLC: Current Employment. Leblanc:AbbVie, Agios, Amgen, AstraZeneca, CareVive, BMS/Celgene, Daiichi-Sankyo, Flatiron, Helsinn, Heron, Otsuka, Medtronic, Pfizer, Seattle Genetics, Welvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; American Cancer Society, BMS, Duke University, NINR/NIH, Jazz Pharmaceuticals, Seattle Genetics: Research Funding; UpToDate: Patents & Royalties: Royalties; Agios, AbbVie, and Bristol Myers Squibb/Celgene: Speakers Bureau; AstraZeneca: Research Funding.

scholarly journals POS1201 Incidence and outcome of COVID-19 in ANCA-associated vasculitis: impact of COVID-19 in patients undergoing rituximab for maintenance

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 883.1-883
Author(s):  
E. Treppo ◽  
M. Binutti ◽  
G. Del Frate ◽  
S. De Vita ◽  
L. Quartuccio
Keyword(s):  
Immunosuppressive Agents ◽  
Geographical Area ◽  
Disease Onset ◽  
Biologic Agent ◽  
Igg Antibodies ◽  
Pharyngeal Swab ◽  
Anca Associated Vasculitis ◽  
The Mean ◽  
Anti Cd20 ◽  
The Impact

Background:COVID-19 is an emerging infectious disease caused by SARS-CoV-2. Risk factors for the worst outcome in COVID-19 are pre-existing pulmonary and cardiovascular disease, while the impact of chronic immunosuppression has not yet completely been clarified (1).Currently, there is no clinical evidence that chronically immunosuppressed rheumatic patients under biologic agent or a small molecule may have a higher risk of COVID-19 or a worse prognosis(2). However, the anti-CD20 antibody monoclonal rituximab may contribute to severe consequences, inhibiting the humoral response to SARS-CoV-2 and capacity to produce efficient antibodies against it (3,4). Rituximab is widely use in the treatment of ANCA-associated vasculitis (AAV). Nowadays, the incidence and impact of COVID-19 in AAV-patients are still unknown and, in particular, in AAV-patients who have been exposed to rituximab since the outbreak (5).Objectives:Herein we evaluate the incidence and outcome of SARS-CoV-2 infection in our cohort of AAV-patients who had at least one visit in the year 2020.Methods:We collected clinical data of 100 AAV-patients who had at least one visit in our Centre from February 2020 to December 2020, and we described cases of COVID-19 infection among them. The COVID-19 was proved by detection of SARS-CoV-2 RNA in nose-pharyngeal swabs. In case of infection, anti-SARS-CoV-2 IgM or IgG production was then investigated.Results:Among 100 patients (53 females; 47 males) regularly followed, the median age was 65, and the mean (SD) duration of disease was 8.8 (6.8) years. The most frequent diagnosis was granulomatosis with polyangiitis (GPA) (56%), followed by granulomatosis eosinophilic with polyangiitis (EGPA) (31%), and microscopic polyangiitis (MPA) (13%). The mean (SD) BVASv3 at the onset of disease was 12.6 (5.6). More than half of the patients (59%) have had lung and/or ENT involvement at the onset of disease. Overall, 84% of our patients received immunosuppressive agents and 45% also received glucocorticoids (GC). Rituximab was administered in 15% of patients during the pandemic. COVID-19 was diagnosed in 2 cases (2%). Both patients have received rituximab as maintenance: the last rituximab infusion was on November 9, 2020 for patient 1 (female, 73 years old, GPA ANCA-PR3+) and was on August 17, 2020 for patient 2 (female, 74 years old, MPA ANCA-MPO+). Both patients had a BVAS 0 and negative ANCA antibodies at the time of the first positive nose-pharyngeal swab RT-PCR test, on December 24 and on November 25, respectively. Both patients were B-cell depleted and IgG levels were 455 mg/dL and 866 mg/dL, respectively. While patient 1 died due to critically ill COVID-19 pneumonia 25 days after the COVID-19 disease onset, patient 2 remained asymptomatic with nose-pharyngeal swab still positive on day 56 after the first detection. Anti-SARS-CoV-2 IgM or IgG antibodies above the cut-off (cut-off value 10 AU/mL) were absent in patient 1, while in patient 2 a low level of anti-SARS-CoV-2 IgG (39 AU/mL, cut-off value 10 AU/mL) was documented.Conclusion:Prevalence of COVID-19 in AAV seems lower than in general population (prevalence of 29582/466700, 6.3%, in the same geographical area). Rituximab compromises the B-cells function and can lead to humoral immunodeficiency, causing the inability to produce anti-SARS-CoV-2 IgG antibodies. The timing of the last rituximab infusion and the levels of IgG can greatly affect the outcome. Patients who underwent anti-CD20 therapy are at higher risk of severe outcome in case of infection (3), and require prioritization for SARS-CoV-2 vaccination.References:[1]Guilpain P, et al. Ann Rheum Dis. 2021;80(1):e10.[2]Quartuccio L, et al. Joint Bone Spine. 2020;87(5):439–43.[3]Benucci M, et al. Ann Rheum Dis. 2020; Aug 4:annrheumdis-2020-218590.[4]Tepasse P-R, et al. Br J Haematol. 2020;190(2):185–8.[5]Kant S, et al. J Nephrol. 2020; J Nephrol. 2020 Oct 8:1-6.Disclosure of Interests:None declared.

scholarly journals AB0400 URINARY ALBUMIN-TO-CREATININE RATIO INDICATES NECROTIZING AND CRESCENTIC GLOMERULONEPHRITISIN ANCA-ASSOCIATED VASCULITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1228-1228
Author(s):  
S. Hakroush ◽  
B. Tampe
Keyword(s):  
Kidney Function ◽  
Renal Involvement ◽  
Disease Onset ◽  
Urinary Albumin ◽  
Histopathological Diagnosis ◽  
Creatinine Ratio ◽  
Short Term ◽  
Anca Associated Vasculitis ◽  
Renal Biopsies ◽  
Severe Deterioration

Background:Renal involvement is a common and severe complication of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) as it can cause acute kidney injury (AKI), end-stage renal disease (ESRD) or death.Objectives:We have previously reported that elevated urinary albumin-to-creatinine ratio (uACR) correlates with rapid deterioration of kidney function in ANCA GN. Therefore, we here aimed to describe the association between proteinuric findings and histopathological diagnosis of necrotizing and crescentic ANCA GN in 50 urinary samples at admission and corresponding renal biopsies of patients with AAV.Methods:A total number of 50 urinary samples at admission and corresponding renal biopsies with confirmed renal involvement of AAV were retrospectively included between 2015 till 2020 in a single-center observational study.Results:Renal involvement of AAV revealed variable proteinuria ranging from low-range to nephrotic syndromes, however most patients presented with subnephrotic proteinuria. Severe deterioration of kidney function requiring RRT within 30 days after admission was associated with elevated levels of nonselective proteinuria, mostly attributed to albuminuria (uACR). Because we have previously shown that histologically confirmed ANCA GN with glomerular crescents and necrosis is associated with AKI and requirement of RRT during short-term disease course and elevated uACR levels were equally associated with AKI and requirement of RRT during the short-term course after disease onset, we next analyzed the association between uACR measurements at admission and histopathological findings within renal biopsies performed thereafter. Severely increased uACR levels >300 mg/g correlated with reduction of normal glomeruli, attributed to increased glomerular crescents and necrosis. By contrast, no such association was observed for global sclerotic glomeruli, revealing that uACR reflects crescentic ANCA GN rather than adaptive glomerular hyperfilitration in chronic sclerosing stage. Since uACR levels could reflect both, either a specific renal involvement with necrotizing and crescentic ANCA GN or severity of systemic AAV disease, we next correlated uACR levels assessed at admission with extrarenal disease manifestation. We observed no association between uACR levels and extrarenal manifestation of AAV disease including pulmonary hemorrhage, skin involvement and BVAS assessment, suggesting that uACR levels reflected specific renal involvement in AAV. These observations were further confirmed by survival analysis for cumulative incidence of RRT during the short-term course of disease.Conclusion:Early identification of patients who mostly benefit from aggressive immunosuppressive therapy is of clinical importance. Our observation that uACR levels at disease onset predict necrotizing and crescentic ANCA GN requires further investigation for therapeutic decision especially in patients with severe deterioration of kidney function.Disclosure of Interests:None declared

Do we Need Maintenance Chemotherapy in Advanced NSCLC in the Era of Immune and Targeted Therapy?

2019 ◽  
Vol 15 (1) ◽  
pp. 50-55
Author(s):  
Ahmed Nagy ◽  
Omar Abdel Rahman ◽  
Heba Abdullah ◽  
Ahmed Negida
Keyword(s):  
Lung Cancer ◽  
Maintenance Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Statistical Significance ◽  
Small Cell ◽  
Maintenance Chemotherapy ◽  
Small Cell Lung ◽  
The Impact

Background: Although well established for the effective management of hematologic cancers, maintenance chemotherapy has only been recently incorportated as a treatment paradigm for advanced non–small-cell lung cancer. Maintenance chemotherapy aims to prolong a clinically favorable response state achieved after finishing induction therapy which is usually predefined in number before startng treatment. There are 2 modalities for maintenance therapy; continuation maintenance (involving a non-platinum component which was a part of the induction protocol or a targeted agent) and switch maintenance therapy (utilizing a new agent which was not a part of the induction regimen). Methods: The purpose of this article is to review the role of maintenance therapy in the treatment of advanced Non-Small Cell Lung Cancer (NSCLC) and provide a brief overview about induction chemotherapy in NSCLC to address the basis of maintenance therapy as a treatment option. We will also compare the impact of maintenance chemotherapy with the now evolving role of immunotherapy in NSCLC. Results: There have been 4 maintenance studies to date showing prolonged PFS and OS with statistical significance. However, Three out of the four studies (ECOG4599, JMEN, and PARAMOUNT) did not report tumor molecular analysis. As regard Immunotherapy, current data is in favour of strongly an increasing role for immunotherapy in NSCLC. Conclusion: Maintenance therapy in NSCLC continues to be an important therapeutic line to improve outcome in patients with metastatic and recurrent disease.

scholarly journals KUALITAS AIR SUNGAI DI KAWASAN WISATA PANTAI PETITENGET, KEROBOKAN KABUPATEN BADUNG BALI

2018 ◽  
Vol 12 (2) ◽  
pp. 226
Author(s):  
Wayan Budiarsa Suyasa ◽  
Sri Kunti Pancadewi G. A ◽  
Iryanti E. Suprihatin ◽  
Dwi Adi Suastuti G. A.
Keyword(s):  
Water Quality ◽  
Structural Changes ◽  
Pollution Index ◽  
Basic Structure ◽  
Physical Damage ◽  
E Coli ◽  
Pollutant Source ◽  
Quality Category ◽  
Index Value ◽  
The Impact

In order to maintain the environmental carrying capacity of coastal tourism, this research was conducted to determine the condition of river water environmental pollution in the Petitenget beach area and pollutant source activities. Determination of water quality is carried out by analyzing the water quality taken at several sampling points in the four rivers that lead to the Petitenget beach. Determined the pollution index value (IP) of the physical chemical and biological pollution parameters. The results showed that the four rivers that flow into the Petitenget Beach area had been contaminated with indications of pH, BOD, COD, ammonia, Coliform and E. coli which exceeded water quality category III class quality (PerGub Bali No 16 Year 2016). The four rivers are included in the criteria of severe contamination. The four rivers have experienced physical damage or structural changes that have very high discharge fluctuations both in quantity and quality. Slimy basic structure, smelly and slum aesthetic waters. While the indication of the impact of pollution is waste water which is directly discharged into the river from hotels, restaurants, homestays, commercial centers and settlements.

scholarly journals POS1121 DEMOGRAPHICS, COMORBIDITIES, AND RENAL FUNCTION OF UNCONTROLLED GOUT PATIENTS WHO RECEIVED PEGLOTICASE: FINDING FROM A LARGE US CLAIMS DATABASE

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 839.2-840
Author(s):  
C. Vesel ◽  
A. Morton ◽  
M. Francis-Sedlak ◽  
B. Lamoreaux
Keyword(s):  
Kidney Function ◽  
Real World ◽  
Randomized Clinical Trials ◽  
Small Subset ◽  
Phase 3 ◽  
Claims Database ◽  
Medical Diagnoses ◽  
Ckd Stage ◽  
Before And After ◽  
The Impact

Background:NHANES data indicate that approximately 9.2 million Americans have gout,1 with a small subset having uncontrolled disease.2 Pegloticase is a PEGylated recombinant uricase enzyme indicated for treating uncontrolled gout that markedly reduces serum uric acid levels (sUA)3 and resolves tophi in treatment responders.4 Despite pegloticase availability in the US for many years, real world demographics of pegloticase users in the treatment of uncontrolled gout have not been previously reported in a population-based cohort.Objectives:This study utilized a large US claims database to examine demographics and co-morbidities of uncontrolled gout patients treated with pegloticase. Kidney function before and after pegloticase treatment and concomitant therapy with immunomodulators were also examined.Methods:The TriNetX Diamond database includes de-identified data from 4.3 million US patients with gout (as of September 2019), including demographics, medical diagnoses, laboratory values, procedures (e.g. infusions, surgeries), and pharmacy data. Patients who had received ≥1 pegloticase infusion were included in these analyses. The number of infusions was evaluated for a subgroup of patients who were in the database ≥3 months before and ≥2 years after the first pegloticase infusion (i.e. first infusion prior to September 2017) to ensure only complete courses of therapy were captured. In this subpopulation, kidney function before and after pegloticase therapy was examined, along with the presence of immunomodulation prescriptions (methotrexate, mycophenolate mofetil, azathioprine, leflunomide) within 60 days prior to and 14 days after the first pegloticase infusion.Results:1494 patients treated with pegloticase were identified. Patients were 63.1 ± 14.0 years of age (range: 23–91), mostly male (82%), and white (76%). Mean sUA prior to pegloticase was 8.7 ± 2.4 mg/dL (n=50), indicating uncontrolled gout in the identified population. The most commonly reported comorbidities were chronic kidney disease (CKD, 48%), essential hypertension (71%), type 2 diabetes (39%), and cardiovascular disease (38%), similar to pegloticase pivotal Phase 3 trial populations. In patients with pre-therapy kidney function measures (n=134), pre-treatment eGFR averaged 61.2 ± 25.7 ml/min/1.73 m2, with 44% having Stage 3-5 CKD. In patients with complete therapy course capture and pre- and post-therapy eGFR measures (n=48), kidney function remained stable (change in eGFR: -2.9 ± 18.2 ml/min/1.73 m2) and CKD stage remained the same or improved in 81% of patients. In 791 patients with complete treatment course capture, patients had received 8.7 ± 13.8 infusions (median: 3, IQR: 2-10). Of these, 189 (24%) patients received only 1 pegloticase infusion and 173 (22%) received ≥12 infusions. As the data cut-off for this analysis pre-dated emerging data on the use of immunomodulation as co-therapy, only 19 of 791 (2%) patients received immunomodulation co-therapy with pegloticase.Conclusion:This relatively large group of patients with uncontrolled gout treated with pegloticase had similar patient characteristics of those studied in the phase 3 randomized clinical trials. Patients with uncontrolled gout are significantly burdened with systemic co-morbid diseases. The majority of patients had stable or improved kidney function following pegloticase treatment. As these results reflect patients initiating treatment prior to 2018, before co-treatment with immunomodulation was introduced, this cohort only included a small percentage of patients who were co-treated with an immunomodulator. Future studies using more current datasets are needed to evaluate real world outcomes in patients treated with pegloticase/immunomodulator co-therapy and to evaluate the impact of systemic co-morbid diseases.References:[1]Chen-Xu M, et al. Arthritis Rheumatol 2019 71:991-999.[2]Fels E, Sundy JS. Curr Opin Rheumatol 2008;20:198-202.[3]Sundy J, et al. JAMA 2011;306:711-720.[4]Mandell BF, et al. Arthritis Res Ther 2018;20:286.Disclosure of Interests:Claudia Vesel Shareholder of: Horizon Therapeutics plc, Employee of: Horizon Therapeutics plc, Allan Morton Speakers bureau: Sanofi, Amgen, and Horizon, Megan Francis-Sedlak Shareholder of: Horizon Therapeutics plc, Employee of: Horizon Therapeutics plc, Brian LaMoreaux Shareholder of: Horizon Therapeutics plc, Employee of: Horizon Therapeutics plc.

Stock Market Volatility and Terrorism: New Evidence from the Markov Switching Model

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Faheem Aslam ◽  
Hyoung-Goo Kang ◽  
Khurrum Shahzad Mughal ◽  
Tahir Mumtaz Awan ◽  
Yasir Tariq Mohmand
Keyword(s):  
Stock Market ◽  
Significant Risk ◽  
Market Volatility ◽  
Terrorist Attacks ◽  
Stock Market Volatility ◽  
Markov Switching Model ◽  
Physical Damage ◽  
Stock Market Returns ◽  
Switching Model ◽  
The Impact

AbstractTerrorism in Pakistan poses a significant risk towards the lives of people by violent destruction and physical damage. In addition to human loss, such catastrophic activities also affect the financial markets. The purpose of this study is to examine the impact of terrorism on the volatility of the Pakistan stock market. The financial impact of 339 terrorist attacks for a period of 18 years (2000–2018) is estimated w.r.t. target type, days of the week, and surprise factor. Three important macroeconomic variables namely exchange rate, gold, and oil were also considered. The findings of the EGARCH (1, 1) model revealed that the terrorist attacks targeting the security forces and commercial facilities significantly increased the stock market volatility. The significant impact of terrorist attacks on Monday, Tuesday, and Thursday confirms the overreaction of investors to terrorist news. Furthermore, the results confirmed the negative linkage between the surprise factor and stock market returns. The findings of this study have significant implications for investors and policymakers.

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