Nader Khan - Academia.edu (original) (raw)

Papers by Nader Khan

Research paper thumbnail of Analyses of up to 8 Years of Treatment from the Abatacept Clinical Trial Program

Objective. To assess the overall safety, including rare events, of intravenous (IV) abatacept tre... more Objective. To assess the overall safety, including rare events, of intravenous (IV) abatacept treatment in rheumatoid arthritis (RA). Methods. Data from 8 clinical trials of IV abatacept in RA were pooled. Safety events were assessed during the short-term (duration ≤ 12 months) and cumulative (short-term plus longterm extensions) abatacept treatment periods. Incidence rates per 100 patient-years were calculated. Standardized incidence ratios (SIR) for hospitalized infections and malignancies were compared with external RA cohorts and, for malignancies, with the US general population. Results. There were 3173 IV abatacept-treated patients with 2331 patient-years of exposure in the short-term periods, and 4149 IV abatacept-treated patients with 12,132 patient-years of exposure in the cumulative period. Incidence rates for serious infections were low and consistent over time (3.68 for abatacept vs 2.60 for placebo during the short-term, and 2.87 for abatacept during the cumulative period). Hospitalized infections were generally similar to external RA patient cohorts and were consistent over time. Incidence rates of malignancies were similar for abatacept-and placebo-treated patients during the short-term period (0.73 vs 0.59) and remained low during the abatacept cumulative period (0.73). SIR of some tissue-specific malignancies (e.g., colorectal and breast) in the cumulative period tended to be lower, while others (lymphoma and lung) tended to be higher, compared with the general population; however, incidence rates were comparable with RA cohorts. Autoimmune events were rare and infusion reactions uncommon. Conclusion. Longterm safety of IV abatacept was consistent with the short-term, with no unexpected events and low incidence rates of serious infections, malignancies, and autoimmune events.

Research paper thumbnail of Personal non-commercial use only

ABSTRACT. Objective. Behçet disease (BD) is a multifactorial disease in which infectious agents h... more ABSTRACT. Objective. Behçet disease (BD) is a multifactorial disease in which infectious agents have been proposed as triggers in genetically predisposed individuals. The aim of our study was to investigate the role of innate immunity receptors, specifically the nucleic acid sensors, in susceptibility to BD. Methods. Seventy-four tag single nucleotide polymorphisms (tSNP) selected in 9 candidate genes (DDX58, IFIH1, TLR3, TLR7, TLR8, AIM2, IFI16, ZBP1, and TLR9) were genotyped in 371 patients and 854 controls. Assays of mRNA expression and allele-specific transcript quantification (ASTQ) were performed in 110 and 50 controls, respectively. Results. Patients and controls were genotyped and 2 tSNP (rs6940 in IFI16 and rs855873 in AIM2) were associated with BD. To confirm this association, these tSNP were genotyped in 850 additional controls, and the total cohort was randomly divided into 2 cohorts. The association of these 2 tSNP with the disease remained in both cohorts. One haplotyp...

Research paper thumbnail of Long‐term safety and efficacy results in hepatitis C virus genotype 1‒infected patients receiving ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin in the TOPAZ‐I and TOPAZ‐II trials

Journal of Viral Hepatitis, 2020

The 3-DAA regimen consisting of ombitasvir/paritaprevir/ritonavir plus dasabuvir (OBV/PTV/r + DSV... more The 3-DAA regimen consisting of ombitasvir/paritaprevir/ritonavir plus dasabuvir (OBV/PTV/r + DSV) ± ribavirin (RBV) has shown high sustained virologic response rates (~95%) in phase 3 clinical trials including>2300 HCV genotype 1-infected patients. Real-world evidence studies have confirmed the effectiveness of OBV/PTV/r ± DSV ± RBV in patients with chronic HCV genotype 1 infection and are consistent with clinical trial results. TOPAZ-I and TOPAZ-II are ongoing phase 3b trials, assessing safety, efficacy and long-term progression of liver disease and clinical outcomes for up to 5 years post-treatment in patients treated with OBV/PTV/r + DSV ± RBV. High rates of sustained virologic response (SVR) wereachieved regardless of presence or absence of cirrhosis. In this report, we assessed the long-term progression of liver disease and incidence of clinical outcomes up to 3 years of post-treatment follow-up in patients with chronic HCV GT1 infection who were treated with (OBV/PTV/r + DSV) ± RBV in the TOPAZ-I and TOPAZ-II studies. Improvements were observed in liver disease markers including FIB-4, METAVIR, and Child-Pugh scores as well as platelet counts. Clinical outcomes related to long-term progression of liver disease such as liver decompensation were infrequent (<1%).Hepatocellular carcinoma (HCC) occurred in 1.4%of cirrhotic patients.

Research paper thumbnail of Proving the viability of an electrochemical process for the simultaneous extraction of oxygen and production of metal alloys from lunar regolith

Planetary and Space Science, 2019

The development of an efficient process to simultaneously extract oxygen and metals from lunar re... more The development of an efficient process to simultaneously extract oxygen and metals from lunar regolith by way of in-situ resource utilisation (ISRU) has the potential to enable sustainable activities beyond Earth. The Metalysis-FFC (Fray, Farthing, Chen) process has recently been proven for the industrial-scale production of metals and alloys, leading to the present investigation into the potential application of this process to regolith-like 2 materials. This paper provides a proof-of-concept for the electro-deoxidation of powdered solid-state lunar regolith simulant using an oxygen-evolving SnO2 anode, and constitutes the first in-depth study of regolith reduction by this process that fully characterises and quantifies both the anodic and cathodic products. Analysis of the resulting metallic powder shows that 96% of the total oxygen was successfully extracted to give a mixed metal alloy product. Approximately a third of the total oxygen in the sample was detected in the off-gas, with the remaining oxygen being lost to corrosion of the reactor vessel. We anticipate, with appropriate adjustments to the experimental setup and operating parameters, to be able to isolate essentially all of the oxygen from lunar regolith simulants using this process, leading to the exciting possibility of concomitant oxygen generation and metal alloy production on the lunar surface.

Research paper thumbnail of SAT-255-Long-term safety and efficacy results in hepatitis C virus genotype 1-infected patients receiving ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin in the TOPAZ-I and TOPAZ-II trials

Journal of Hepatology, 2019

therapies, the 3-year incidence of de novo HCC was 3%, and of recurrence was 49.2%. Propensity sc... more therapies, the 3-year incidence of de novo HCC was 3%, and of recurrence was 49.2%. Propensity score-matched analysis showed no significant difference in de novo HCC (p = 0.137) and recurrence (p = 0.150) rates among groups treated with IFNbased or IFN-free therapies. In univariate and multivariate analysis, post-treatment WFA + M2BP level was independently associated with de novo HCC (p = 0.032, HR (95%CI) = 3.367 (0.098-0.902)), and posttreatment AFP level with recurrence after SVR (p = 0.038, HR (95%CI) = 2.907 (0.125-0.943)). Although significant difference was not found so far (p = 0.143), among patients with previous history of HCC, the 3-year survival rate was 92.6% for IFN-based, and 82.4% for IFN-free treatment respectively. Conclusion: Propensity score-matched analysis showed no significant difference in de novo HCC and recurrence rates among groups treated with IFN-based or IFN-free therapies. Although significant difference was not found so far, among patients with previous history of HCC, the 3-year survival rate was lower in patients treated with IFN-free therapy, so longer-term longitudinal studies about cumulative incidences of survival in larger cohorts are required to reveal the prognostic improvement for CHC patients.

Research paper thumbnail of Epidemiology of potential drug-drug interactions in elderly population admitted to critical care units of Peshawar, Pakistan

BMC Pharmacology and Toxicology, 2018

Background: Aging population, is a reality in many countries because of improvement in the health... more Background: Aging population, is a reality in many countries because of improvement in the health care, patient safety and other supplemental factors. Pharmacotherapy in this population must be evaluated due to their higher susceptibility to adverse drug outcomes, like potential drug-drug interactions (PDDIs). Research in this regard is limited particularly in developing countries. The aim of the study was to evaluate the prevalence and associated factors in this population. Methods: The multicentered study evaluated the prevalence of potential drug-drug interactions and associated factors in elderly population at critical care units in Peshawar, Pakistan. Potential drug-drug interactions were evaluated using Micromedex DrugReax, while statistical analysis was performed using SPSS. Results: A total of 70.17% elderly patients were observed to have at least one PDDI. A significant association was observed between presence of PDDIs and number of prescribed drugs, duration of stay and age (p < 0.05). A total of 3019 PDDIs were observed, attributing to 225 drug pairs. Prevalent PDDIs were of moderate severity, good documentation and pharmacodynamic in nature. One-way ANOVA revealed a significant difference in the means of PDDIs between Northwest general hospital and the rest of the hospitals. Moreover, there was a significant difference in the means of PDDIs of CCU and SU with rest of the units. Conclusion: The prevalence of PDDIs was observed to be high in elderly population which can be managed by avoiding or managing a limited number of drug combinations. Such studies are necessary to evaluate the risks of these PDDIs in a population which is already physiologically compromised.

Research paper thumbnail of Safety of Abatacept Administered Intravenously in Treatment of Rheumatoid Arthritis: Integrated Analyses of up to 8 Years of Treatment from the Abatacept Clinical Trial Program

The Journal of Rheumatology, 2013

Objective.To assess the overall safety, including rare events, of intravenous (IV) abatacept trea... more Objective.To assess the overall safety, including rare events, of intravenous (IV) abatacept treatment in rheumatoid arthritis (RA).Methods.Data from 8 clinical trials of IV abatacept in RA were pooled. Safety events were assessed during the short-term (duration ≤ 12 months) and cumulative (short-term plus longterm extensions) abatacept treatment periods. Incidence rates per 100 patient-years were calculated. Standardized incidence ratios (SIR) for hospitalized infections and malignancies were compared with external RA cohorts and, for malignancies, with the US general population.Results.There were 3173 IV abatacept-treated patients with 2331 patient-years of exposure in the short-term periods, and 4149 IV abatacept-treated patients with 12,132 patient-years of exposure in the cumulative period. Incidence rates for serious infections were low and consistent over time (3.68 for abatacept vs 2.60 for placebo during the short-term, and 2.87 for abatacept during the cumulative period). ...

Research paper thumbnail of Linked Parallel Synthesis and MTT Bioassay Screening of Substituted Chalcones

Journal of Combinatorial Chemistry, 2001

A 644-membered library of chalcones was prepared by parallel synthesis using the Claisen-Schmidt ... more A 644-membered library of chalcones was prepared by parallel synthesis using the Claisen-Schmidt basecatalyzed aldol condensation of substituted acetophenones and benzaldehydes. The cytotoxicity of these chalcones was conveniently determined upon the crude products directly in 96-well microtiter test plates by the conventional MTT assay. This method revealed seven chalcones of IC 50 less than 1 µM of which 4′hydroxy-2,4,6,3′-tetramethoxychalcone (5a) was the most active [IC 50 (K562), 30 nM]; it causes cell cycle arrest at the G 2 /M point and binds to tubulin at the colchicine binding site.

Research paper thumbnail of Analyses of up to 8 Years of Treatment from the Abatacept Clinical Trial Program

Objective. To assess the overall safety, including rare events, of intravenous (IV) abatacept tre... more Objective. To assess the overall safety, including rare events, of intravenous (IV) abatacept treatment in rheumatoid arthritis (RA). Methods. Data from 8 clinical trials of IV abatacept in RA were pooled. Safety events were assessed during the short-term (duration ≤ 12 months) and cumulative (short-term plus longterm extensions) abatacept treatment periods. Incidence rates per 100 patient-years were calculated. Standardized incidence ratios (SIR) for hospitalized infections and malignancies were compared with external RA cohorts and, for malignancies, with the US general population. Results. There were 3173 IV abatacept-treated patients with 2331 patient-years of exposure in the short-term periods, and 4149 IV abatacept-treated patients with 12,132 patient-years of exposure in the cumulative period. Incidence rates for serious infections were low and consistent over time (3.68 for abatacept vs 2.60 for placebo during the short-term, and 2.87 for abatacept during the cumulative period). Hospitalized infections were generally similar to external RA patient cohorts and were consistent over time. Incidence rates of malignancies were similar for abatacept-and placebo-treated patients during the short-term period (0.73 vs 0.59) and remained low during the abatacept cumulative period (0.73). SIR of some tissue-specific malignancies (e.g., colorectal and breast) in the cumulative period tended to be lower, while others (lymphoma and lung) tended to be higher, compared with the general population; however, incidence rates were comparable with RA cohorts. Autoimmune events were rare and infusion reactions uncommon. Conclusion. Longterm safety of IV abatacept was consistent with the short-term, with no unexpected events and low incidence rates of serious infections, malignancies, and autoimmune events.

Research paper thumbnail of Personal non-commercial use only

ABSTRACT. Objective. Behçet disease (BD) is a multifactorial disease in which infectious agents h... more ABSTRACT. Objective. Behçet disease (BD) is a multifactorial disease in which infectious agents have been proposed as triggers in genetically predisposed individuals. The aim of our study was to investigate the role of innate immunity receptors, specifically the nucleic acid sensors, in susceptibility to BD. Methods. Seventy-four tag single nucleotide polymorphisms (tSNP) selected in 9 candidate genes (DDX58, IFIH1, TLR3, TLR7, TLR8, AIM2, IFI16, ZBP1, and TLR9) were genotyped in 371 patients and 854 controls. Assays of mRNA expression and allele-specific transcript quantification (ASTQ) were performed in 110 and 50 controls, respectively. Results. Patients and controls were genotyped and 2 tSNP (rs6940 in IFI16 and rs855873 in AIM2) were associated with BD. To confirm this association, these tSNP were genotyped in 850 additional controls, and the total cohort was randomly divided into 2 cohorts. The association of these 2 tSNP with the disease remained in both cohorts. One haplotyp...

Research paper thumbnail of Long‐term safety and efficacy results in hepatitis C virus genotype 1‒infected patients receiving ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin in the TOPAZ‐I and TOPAZ‐II trials

Journal of Viral Hepatitis, 2020

The 3-DAA regimen consisting of ombitasvir/paritaprevir/ritonavir plus dasabuvir (OBV/PTV/r + DSV... more The 3-DAA regimen consisting of ombitasvir/paritaprevir/ritonavir plus dasabuvir (OBV/PTV/r + DSV) ± ribavirin (RBV) has shown high sustained virologic response rates (~95%) in phase 3 clinical trials including>2300 HCV genotype 1-infected patients. Real-world evidence studies have confirmed the effectiveness of OBV/PTV/r ± DSV ± RBV in patients with chronic HCV genotype 1 infection and are consistent with clinical trial results. TOPAZ-I and TOPAZ-II are ongoing phase 3b trials, assessing safety, efficacy and long-term progression of liver disease and clinical outcomes for up to 5 years post-treatment in patients treated with OBV/PTV/r + DSV ± RBV. High rates of sustained virologic response (SVR) wereachieved regardless of presence or absence of cirrhosis. In this report, we assessed the long-term progression of liver disease and incidence of clinical outcomes up to 3 years of post-treatment follow-up in patients with chronic HCV GT1 infection who were treated with (OBV/PTV/r + DSV) ± RBV in the TOPAZ-I and TOPAZ-II studies. Improvements were observed in liver disease markers including FIB-4, METAVIR, and Child-Pugh scores as well as platelet counts. Clinical outcomes related to long-term progression of liver disease such as liver decompensation were infrequent (<1%).Hepatocellular carcinoma (HCC) occurred in 1.4%of cirrhotic patients.

Research paper thumbnail of Proving the viability of an electrochemical process for the simultaneous extraction of oxygen and production of metal alloys from lunar regolith

Planetary and Space Science, 2019

The development of an efficient process to simultaneously extract oxygen and metals from lunar re... more The development of an efficient process to simultaneously extract oxygen and metals from lunar regolith by way of in-situ resource utilisation (ISRU) has the potential to enable sustainable activities beyond Earth. The Metalysis-FFC (Fray, Farthing, Chen) process has recently been proven for the industrial-scale production of metals and alloys, leading to the present investigation into the potential application of this process to regolith-like 2 materials. This paper provides a proof-of-concept for the electro-deoxidation of powdered solid-state lunar regolith simulant using an oxygen-evolving SnO2 anode, and constitutes the first in-depth study of regolith reduction by this process that fully characterises and quantifies both the anodic and cathodic products. Analysis of the resulting metallic powder shows that 96% of the total oxygen was successfully extracted to give a mixed metal alloy product. Approximately a third of the total oxygen in the sample was detected in the off-gas, with the remaining oxygen being lost to corrosion of the reactor vessel. We anticipate, with appropriate adjustments to the experimental setup and operating parameters, to be able to isolate essentially all of the oxygen from lunar regolith simulants using this process, leading to the exciting possibility of concomitant oxygen generation and metal alloy production on the lunar surface.

Research paper thumbnail of SAT-255-Long-term safety and efficacy results in hepatitis C virus genotype 1-infected patients receiving ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin in the TOPAZ-I and TOPAZ-II trials

Journal of Hepatology, 2019

therapies, the 3-year incidence of de novo HCC was 3%, and of recurrence was 49.2%. Propensity sc... more therapies, the 3-year incidence of de novo HCC was 3%, and of recurrence was 49.2%. Propensity score-matched analysis showed no significant difference in de novo HCC (p = 0.137) and recurrence (p = 0.150) rates among groups treated with IFNbased or IFN-free therapies. In univariate and multivariate analysis, post-treatment WFA + M2BP level was independently associated with de novo HCC (p = 0.032, HR (95%CI) = 3.367 (0.098-0.902)), and posttreatment AFP level with recurrence after SVR (p = 0.038, HR (95%CI) = 2.907 (0.125-0.943)). Although significant difference was not found so far (p = 0.143), among patients with previous history of HCC, the 3-year survival rate was 92.6% for IFN-based, and 82.4% for IFN-free treatment respectively. Conclusion: Propensity score-matched analysis showed no significant difference in de novo HCC and recurrence rates among groups treated with IFN-based or IFN-free therapies. Although significant difference was not found so far, among patients with previous history of HCC, the 3-year survival rate was lower in patients treated with IFN-free therapy, so longer-term longitudinal studies about cumulative incidences of survival in larger cohorts are required to reveal the prognostic improvement for CHC patients.

Research paper thumbnail of Epidemiology of potential drug-drug interactions in elderly population admitted to critical care units of Peshawar, Pakistan

BMC Pharmacology and Toxicology, 2018

Background: Aging population, is a reality in many countries because of improvement in the health... more Background: Aging population, is a reality in many countries because of improvement in the health care, patient safety and other supplemental factors. Pharmacotherapy in this population must be evaluated due to their higher susceptibility to adverse drug outcomes, like potential drug-drug interactions (PDDIs). Research in this regard is limited particularly in developing countries. The aim of the study was to evaluate the prevalence and associated factors in this population. Methods: The multicentered study evaluated the prevalence of potential drug-drug interactions and associated factors in elderly population at critical care units in Peshawar, Pakistan. Potential drug-drug interactions were evaluated using Micromedex DrugReax, while statistical analysis was performed using SPSS. Results: A total of 70.17% elderly patients were observed to have at least one PDDI. A significant association was observed between presence of PDDIs and number of prescribed drugs, duration of stay and age (p < 0.05). A total of 3019 PDDIs were observed, attributing to 225 drug pairs. Prevalent PDDIs were of moderate severity, good documentation and pharmacodynamic in nature. One-way ANOVA revealed a significant difference in the means of PDDIs between Northwest general hospital and the rest of the hospitals. Moreover, there was a significant difference in the means of PDDIs of CCU and SU with rest of the units. Conclusion: The prevalence of PDDIs was observed to be high in elderly population which can be managed by avoiding or managing a limited number of drug combinations. Such studies are necessary to evaluate the risks of these PDDIs in a population which is already physiologically compromised.

Research paper thumbnail of Safety of Abatacept Administered Intravenously in Treatment of Rheumatoid Arthritis: Integrated Analyses of up to 8 Years of Treatment from the Abatacept Clinical Trial Program

The Journal of Rheumatology, 2013

Objective.To assess the overall safety, including rare events, of intravenous (IV) abatacept trea... more Objective.To assess the overall safety, including rare events, of intravenous (IV) abatacept treatment in rheumatoid arthritis (RA).Methods.Data from 8 clinical trials of IV abatacept in RA were pooled. Safety events were assessed during the short-term (duration ≤ 12 months) and cumulative (short-term plus longterm extensions) abatacept treatment periods. Incidence rates per 100 patient-years were calculated. Standardized incidence ratios (SIR) for hospitalized infections and malignancies were compared with external RA cohorts and, for malignancies, with the US general population.Results.There were 3173 IV abatacept-treated patients with 2331 patient-years of exposure in the short-term periods, and 4149 IV abatacept-treated patients with 12,132 patient-years of exposure in the cumulative period. Incidence rates for serious infections were low and consistent over time (3.68 for abatacept vs 2.60 for placebo during the short-term, and 2.87 for abatacept during the cumulative period). ...

Research paper thumbnail of Linked Parallel Synthesis and MTT Bioassay Screening of Substituted Chalcones

Journal of Combinatorial Chemistry, 2001

A 644-membered library of chalcones was prepared by parallel synthesis using the Claisen-Schmidt ... more A 644-membered library of chalcones was prepared by parallel synthesis using the Claisen-Schmidt basecatalyzed aldol condensation of substituted acetophenones and benzaldehydes. The cytotoxicity of these chalcones was conveniently determined upon the crude products directly in 96-well microtiter test plates by the conventional MTT assay. This method revealed seven chalcones of IC 50 less than 1 µM of which 4′hydroxy-2,4,6,3′-tetramethoxychalcone (5a) was the most active [IC 50 (K562), 30 nM]; it causes cell cycle arrest at the G 2 /M point and binds to tubulin at the colchicine binding site.