Eliza Pontifex - Academia.edu (original) (raw)

Papers by Eliza Pontifex

Research paper thumbnail of Prevalence of minimal disease activity in Australian patients with Psoriatic Arthritis: Assessing the outcome of national funding criteria for biologic disease-modifying antirheumatic drug prescribing

International Journal of Rheumatic Diseases

Research paper thumbnail of Prevalence of minimal disease activity in Australian patients with Psoriatic Arthritis: Assessing the outcome of national funding criteria for biologic disease-modifying antirheumatic drug prescribing

International Journal of Rheumatic Diseases

Research paper thumbnail of Prevalence of minimal disease activity in Australian patients with Psoriatic Arthritis: Assessing the outcome of national funding criteria for biologic disease-modifying antirheumatic drug prescribing

International Journal of Rheumatic Diseases

Research paper thumbnail of CONTRIBUTORS

Palliative Medicine, 2009

Research paper thumbnail of MRI-Based Visualisation and Quantification of Rheumatoid and Psoriatic Arthritis of the Knee

Mathematics and Visualization, 2012

... of Rheumatoid and Psoriatic Arthritis of the Knee Ben Donlon, Douglas Veale, Patrick Brennan,... more ... of Rheumatoid and Psoriatic Arthritis of the Knee Ben Donlon, Douglas Veale, Patrick Brennan, Robert Gibney, Hamish Carr, Louise Rainford, ChinTeck Ng, Eliza Pontifex, Jonathan McNulty, Oliver FitzGerald, and John Ryan ... 59 5. Vital E, Emery P (Sep 15 2005). ...

Research paper thumbnail of Breast cancer and systemic sclerosis: a clinical description of 21 patients in a population-based cohort study

Rheumatology International, 2008

Previous studies have demonstrated an increased risk of breast cancer among patients with systemi... more Previous studies have demonstrated an increased risk of breast cancer among patients with systemic sclerosis (scleroderma). To describe the clinical characteristics of 21 patients with both systemic sclerosis and breast cancer, and compare their risk factors to female scleroderma patients without breast cancer, in a population-based cohort study of South Australia. Subjects with scleroderma and breast cancer were identified from the South Australian Scleroderma Register with cross-linking to the South Australian Cancer Registry, last updated to the end of December 2005. Clinical information was obtained from standardised self-administered questionnaires and case note reviews. Odds ratios for the risk factors for breast cancer in scleroderma were determined, and clinical variables were analysed using chi square, Fisher's exact, Mann-Whitney and t tests. At the end of December 2005 there were a total of 389 female patients with scleroderma. Of these, 21 (5.4%) had been diagnosed with breast cancer. The mean age of onset of scleroderma was 43.5 years, and the mean age of breast cancer was 60.5 years in those with scleroderma and breast cancer. The majority (71.4%) had limited scleroderma, with anti-centromere antibody being the most prevalent serological abnormality. In 16 (76%) patients the diagnosis of breast cancer occurred on an average of 22.3 years after the onset of their first scleroderma symptom. When compared to 48 controls, scleroderma patients with breast cancer were found to have a higher incidence of a positive family history of breast cancer (Fisher's exact test, p = 0.04) and a lower incidence of hormone-replacement therapy use (Fisher's exact test, p = 0.0026). This population-based cohort study provides evidence that the majority of patients with scleroderma and breast cancer have limited scleroderma and anti-centromere antibody. Given the increased incidence of solid tumours in systemic sclerosis, we suggest regular screening of female patients for breast cancer, especially in those with a family history.

Research paper thumbnail of Synovial Tissue Sublining CD68 Expression Is a Biomarker of Therapeutic Response in Rheumatoid Arthritis Clinical Trials: Consistency Across Centers

The Journal of Rheumatology, 2009

To determine whether the correlation between the mean change in disease activity and the mean cha... more To determine whether the correlation between the mean change in disease activity and the mean change in synovial sublining (sl) CD68 expression could be demonstrated across different academic centers. Synovial biopsies obtained at arthroscopy from patients with rheumatoid arthritis before and 160 days after rituximab therapy were selected and coded. Paired sections were processed independently at Amsterdam Medical Center (AMC) and at St. Vincent's University Hospital (SVUH), Dublin. Digital image analysis (DIA) was employed at both centers to quantify sublining CD68 expression. After analysis of CD68sl expression at centers in 2 different countries, high levels of intracenter and intercenter agreement were observed. For the pooled sections stained at AMC, the correlation between 2 investigators was R = 0.942, p = 0.000, and for sections stained at SVUH, R = 0.899, p = 0.001. Similarly, the intracenter correlations for DeltaCD68sl expression after treatment were R = 0.998, p = 0.000, for sections stained at AMC and R = 0.880, p = 0.000, for sections stained at SVUH. The intercenter correlation for the pooled scores of sections stained at AMC was R = 0.85, p = 0.000, and for the sections stained at SVUH, R = 0.62, p = 0.001. The consistent correlation between DeltaDAS (Disease Activity Score) and DeltaCD68sl expression across different studies (Pearson correlation = 0.895, p < 0.001) was confirmed. The standardized response mean values for DeltaCD68sl, calculated from analyses at both AMC and SVUH, were consistently 0.5 or greater, indicating a moderate to high potential to detect change. The correlation between mean DeltaDAS and mean DeltaCD68sl expression was confirmed across 2 centers. Examination of serial biopsy samples can be used reliably to screen for interesting biological effects at the site of inflammation at an early stage of drug development.

Research paper thumbnail of Remission in psoriatic arthritis: is it possible and how can it be predicted?

Arthritis Research & Therapy, 2010

Introduction: Since remission is now possible in psoriatic arthritis (PsA) we wished to examine r... more Introduction: Since remission is now possible in psoriatic arthritis (PsA) we wished to examine remission rates in PsA patients following anti tumour necrosis factor alpha (TNFα) therapy and to examine possible predictors of response.

Research paper thumbnail of Change in CD3 positive T-cell expression in psoriatic arthritis synovium correlates with change in DAS28 and magnetic resonance imaging synovitis scores following initiation of biologic therapy - a single centre, open-label study

Arthritis Research & Therapy, 2011

Introduction: With the development of increasing numbers of potential therapeutic agents in infla... more Introduction: With the development of increasing numbers of potential therapeutic agents in inflammatory disease comes the need for effective biomarkers to help screen for drug efficacy and optimal dosing regimens early in the clinical trial process. This need has been recognized by the Outcome Measures in Rheumatology Clinical Trials (OMERACT) group, which has established guidelines for biomarker validation. To seek a candidate synovial biomarker of treatment response in psoriatic arthritis (PsA), we determined whether changes in immunohistochemical markers of synovial inflammation correlate with changes in disease activity scores assessing 28 joints (ΔDAS28) or magnetic resonance imaging synovitis scores (ΔMRI) in patients with PsA treated with a biologic agent. Methods: Twenty-five consecutive patients with PsA underwent arthroscopic synovial biopsies and MRI scans of an inflamed knee joint at baseline and 12 weeks after starting treatment with either anakinra (first 10 patients) or etanercept (subsequent 15 patients) in two sequential studies of identical design. DAS28 scores were measured at both time points. Immunohistochemical staining for CD3, CD68 and Factor VIII (FVIII) was performed on synovial samples and scored by digital image analysis (DIA). MRI scans performed at baseline and at 12 weeks were scored for synovitis semi-quantitatively. The ΔDAS28 of the European League Against Rheumatism good response definition (>1.2) was chosen to divide patients into responder and non-responder groups. Differences between groups (Mann Whitney U test) and correlations between ΔDAS28 with change in immunohistochemical and MRI synovitis scores (Spearman's rho test) were calculated. Results: Paired synovial samples and MRI scans were available for 21 patients (8 anakinra, 13 etanercept) and 23 patients (8 anakinra, 15 etanercept) respectively. Change in CD3 (ΔCD3) and CD68 expression in the synovial sublining layer (ΔCD68sl) was significantly greater in the disease responders compared to non-responders following treatment (P = 0.005 and 0.013 respectively). ΔCD3, but not ΔCD68 or ΔFVIII, correlated with both ΔDAS28 (r = 0.49, P = 0.025) and ΔMRI (r = 0.58, P = 0.009). Conclusions: The correlation of ΔCD3 with ΔDAS28 and ΔMRI following biologic treatment in this cohort contributes to the validation of ΔCD3 as a synovial biomarker of disease response in PsA, and supports the further evaluation of ΔCD3 for predictive properties of future clinical outcomes.

Research paper thumbnail of Risk factors for lung cancer in patients with scleroderma: a nested case-control study

Annals of the Rheumatic Diseases, 2006

Objectives: To study potential risk factors for the development of lung cancer in patients with s... more Objectives: To study potential risk factors for the development of lung cancer in patients with scleroderma and explore the chronological relationship between onset of scleroderma symptoms and subtypes of lung cancer. Method: Linkage of two population-based registers to identify lung cancer cases and gender-matched controls with scleroderma, followed by retrospective case note review for clinical details. Results: Patients with scleroderma who smoke are seven times more likely to develop lung cancer than non-smokers (p = 0.008). Smokers with scleroderma and cancer smoke more than smokers with scleroderma without cancer (p = 0.019). Pulmonary fibrosis and anti-topoisomerase antibody do not increase the risk of lung cancer. Peripheral lung tumours occur earlier after the onset of scleroderma symptoms than bronchogenic tumours (p = 0.05).

Research paper thumbnail of A Clinically Based Protein Discovery Strategy to Identify Potential Biomarkers of Response to Anti-TNF-α Treatment of Psoriatic Arthritis

Proteomics. Clinical applications, Jan 24, 2015

Psoriatic arthritis (PsA) can be treated using biologic therapies targeting biomolecules such as ... more Psoriatic arthritis (PsA) can be treated using biologic therapies targeting biomolecules such as tumour necrosis factor alpha, interleukins (IL)-17 and IL-23. Whilst 70% PsA patients respond well to therapy, 30% patients show no or limited clinical improvement. Biomarkers that predict response to therapy would help to avoid unnecessary use of expensive biologics in non-responding patients and enable alternative treatments to be explored. Patient synovial-tissue samples from two clinical studies were analysed using Difference In-Gel Electrophoresis based proteomics to identify protein expression differences in response to anti-TNF-α treatment. Subsequent multiplexed multiple-reaction-monitoring (MRM) measurements were used to verify potential biomarkers. A total of 119 proteins were differentially expressed (p<0.05) in response to anti-TNF-α treatment and 25 proteins were differentially expressed (p<0.05) between "good responders" and "poor responders". From...

Research paper thumbnail of Prevalence of minimal disease activity in Australian patients with Psoriatic Arthritis: Assessing the outcome of national funding criteria for biologic disease-modifying antirheumatic drug prescribing

International Journal of Rheumatic Diseases

Research paper thumbnail of Prevalence of minimal disease activity in Australian patients with Psoriatic Arthritis: Assessing the outcome of national funding criteria for biologic disease-modifying antirheumatic drug prescribing

International Journal of Rheumatic Diseases

Research paper thumbnail of Prevalence of minimal disease activity in Australian patients with Psoriatic Arthritis: Assessing the outcome of national funding criteria for biologic disease-modifying antirheumatic drug prescribing

International Journal of Rheumatic Diseases

Research paper thumbnail of CONTRIBUTORS

Palliative Medicine, 2009

Research paper thumbnail of MRI-Based Visualisation and Quantification of Rheumatoid and Psoriatic Arthritis of the Knee

Mathematics and Visualization, 2012

... of Rheumatoid and Psoriatic Arthritis of the Knee Ben Donlon, Douglas Veale, Patrick Brennan,... more ... of Rheumatoid and Psoriatic Arthritis of the Knee Ben Donlon, Douglas Veale, Patrick Brennan, Robert Gibney, Hamish Carr, Louise Rainford, ChinTeck Ng, Eliza Pontifex, Jonathan McNulty, Oliver FitzGerald, and John Ryan ... 59 5. Vital E, Emery P (Sep 15 2005). ...

Research paper thumbnail of Breast cancer and systemic sclerosis: a clinical description of 21 patients in a population-based cohort study

Rheumatology International, 2008

Previous studies have demonstrated an increased risk of breast cancer among patients with systemi... more Previous studies have demonstrated an increased risk of breast cancer among patients with systemic sclerosis (scleroderma). To describe the clinical characteristics of 21 patients with both systemic sclerosis and breast cancer, and compare their risk factors to female scleroderma patients without breast cancer, in a population-based cohort study of South Australia. Subjects with scleroderma and breast cancer were identified from the South Australian Scleroderma Register with cross-linking to the South Australian Cancer Registry, last updated to the end of December 2005. Clinical information was obtained from standardised self-administered questionnaires and case note reviews. Odds ratios for the risk factors for breast cancer in scleroderma were determined, and clinical variables were analysed using chi square, Fisher&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s exact, Mann-Whitney and t tests. At the end of December 2005 there were a total of 389 female patients with scleroderma. Of these, 21 (5.4%) had been diagnosed with breast cancer. The mean age of onset of scleroderma was 43.5 years, and the mean age of breast cancer was 60.5 years in those with scleroderma and breast cancer. The majority (71.4%) had limited scleroderma, with anti-centromere antibody being the most prevalent serological abnormality. In 16 (76%) patients the diagnosis of breast cancer occurred on an average of 22.3 years after the onset of their first scleroderma symptom. When compared to 48 controls, scleroderma patients with breast cancer were found to have a higher incidence of a positive family history of breast cancer (Fisher&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s exact test, p = 0.04) and a lower incidence of hormone-replacement therapy use (Fisher&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s exact test, p = 0.0026). This population-based cohort study provides evidence that the majority of patients with scleroderma and breast cancer have limited scleroderma and anti-centromere antibody. Given the increased incidence of solid tumours in systemic sclerosis, we suggest regular screening of female patients for breast cancer, especially in those with a family history.

Research paper thumbnail of Synovial Tissue Sublining CD68 Expression Is a Biomarker of Therapeutic Response in Rheumatoid Arthritis Clinical Trials: Consistency Across Centers

The Journal of Rheumatology, 2009

To determine whether the correlation between the mean change in disease activity and the mean cha... more To determine whether the correlation between the mean change in disease activity and the mean change in synovial sublining (sl) CD68 expression could be demonstrated across different academic centers. Synovial biopsies obtained at arthroscopy from patients with rheumatoid arthritis before and 160 days after rituximab therapy were selected and coded. Paired sections were processed independently at Amsterdam Medical Center (AMC) and at St. Vincent&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s University Hospital (SVUH), Dublin. Digital image analysis (DIA) was employed at both centers to quantify sublining CD68 expression. After analysis of CD68sl expression at centers in 2 different countries, high levels of intracenter and intercenter agreement were observed. For the pooled sections stained at AMC, the correlation between 2 investigators was R = 0.942, p = 0.000, and for sections stained at SVUH, R = 0.899, p = 0.001. Similarly, the intracenter correlations for DeltaCD68sl expression after treatment were R = 0.998, p = 0.000, for sections stained at AMC and R = 0.880, p = 0.000, for sections stained at SVUH. The intercenter correlation for the pooled scores of sections stained at AMC was R = 0.85, p = 0.000, and for the sections stained at SVUH, R = 0.62, p = 0.001. The consistent correlation between DeltaDAS (Disease Activity Score) and DeltaCD68sl expression across different studies (Pearson correlation = 0.895, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) was confirmed. The standardized response mean values for DeltaCD68sl, calculated from analyses at both AMC and SVUH, were consistently 0.5 or greater, indicating a moderate to high potential to detect change. The correlation between mean DeltaDAS and mean DeltaCD68sl expression was confirmed across 2 centers. Examination of serial biopsy samples can be used reliably to screen for interesting biological effects at the site of inflammation at an early stage of drug development.

Research paper thumbnail of Remission in psoriatic arthritis: is it possible and how can it be predicted?

Arthritis Research & Therapy, 2010

Introduction: Since remission is now possible in psoriatic arthritis (PsA) we wished to examine r... more Introduction: Since remission is now possible in psoriatic arthritis (PsA) we wished to examine remission rates in PsA patients following anti tumour necrosis factor alpha (TNFα) therapy and to examine possible predictors of response.

Research paper thumbnail of Change in CD3 positive T-cell expression in psoriatic arthritis synovium correlates with change in DAS28 and magnetic resonance imaging synovitis scores following initiation of biologic therapy - a single centre, open-label study

Arthritis Research & Therapy, 2011

Introduction: With the development of increasing numbers of potential therapeutic agents in infla... more Introduction: With the development of increasing numbers of potential therapeutic agents in inflammatory disease comes the need for effective biomarkers to help screen for drug efficacy and optimal dosing regimens early in the clinical trial process. This need has been recognized by the Outcome Measures in Rheumatology Clinical Trials (OMERACT) group, which has established guidelines for biomarker validation. To seek a candidate synovial biomarker of treatment response in psoriatic arthritis (PsA), we determined whether changes in immunohistochemical markers of synovial inflammation correlate with changes in disease activity scores assessing 28 joints (ΔDAS28) or magnetic resonance imaging synovitis scores (ΔMRI) in patients with PsA treated with a biologic agent. Methods: Twenty-five consecutive patients with PsA underwent arthroscopic synovial biopsies and MRI scans of an inflamed knee joint at baseline and 12 weeks after starting treatment with either anakinra (first 10 patients) or etanercept (subsequent 15 patients) in two sequential studies of identical design. DAS28 scores were measured at both time points. Immunohistochemical staining for CD3, CD68 and Factor VIII (FVIII) was performed on synovial samples and scored by digital image analysis (DIA). MRI scans performed at baseline and at 12 weeks were scored for synovitis semi-quantitatively. The ΔDAS28 of the European League Against Rheumatism good response definition (>1.2) was chosen to divide patients into responder and non-responder groups. Differences between groups (Mann Whitney U test) and correlations between ΔDAS28 with change in immunohistochemical and MRI synovitis scores (Spearman's rho test) were calculated. Results: Paired synovial samples and MRI scans were available for 21 patients (8 anakinra, 13 etanercept) and 23 patients (8 anakinra, 15 etanercept) respectively. Change in CD3 (ΔCD3) and CD68 expression in the synovial sublining layer (ΔCD68sl) was significantly greater in the disease responders compared to non-responders following treatment (P = 0.005 and 0.013 respectively). ΔCD3, but not ΔCD68 or ΔFVIII, correlated with both ΔDAS28 (r = 0.49, P = 0.025) and ΔMRI (r = 0.58, P = 0.009). Conclusions: The correlation of ΔCD3 with ΔDAS28 and ΔMRI following biologic treatment in this cohort contributes to the validation of ΔCD3 as a synovial biomarker of disease response in PsA, and supports the further evaluation of ΔCD3 for predictive properties of future clinical outcomes.

Research paper thumbnail of Risk factors for lung cancer in patients with scleroderma: a nested case-control study

Annals of the Rheumatic Diseases, 2006

Objectives: To study potential risk factors for the development of lung cancer in patients with s... more Objectives: To study potential risk factors for the development of lung cancer in patients with scleroderma and explore the chronological relationship between onset of scleroderma symptoms and subtypes of lung cancer. Method: Linkage of two population-based registers to identify lung cancer cases and gender-matched controls with scleroderma, followed by retrospective case note review for clinical details. Results: Patients with scleroderma who smoke are seven times more likely to develop lung cancer than non-smokers (p = 0.008). Smokers with scleroderma and cancer smoke more than smokers with scleroderma without cancer (p = 0.019). Pulmonary fibrosis and anti-topoisomerase antibody do not increase the risk of lung cancer. Peripheral lung tumours occur earlier after the onset of scleroderma symptoms than bronchogenic tumours (p = 0.05).

Research paper thumbnail of A Clinically Based Protein Discovery Strategy to Identify Potential Biomarkers of Response to Anti-TNF-α Treatment of Psoriatic Arthritis

Proteomics. Clinical applications, Jan 24, 2015

Psoriatic arthritis (PsA) can be treated using biologic therapies targeting biomolecules such as ... more Psoriatic arthritis (PsA) can be treated using biologic therapies targeting biomolecules such as tumour necrosis factor alpha, interleukins (IL)-17 and IL-23. Whilst 70% PsA patients respond well to therapy, 30% patients show no or limited clinical improvement. Biomarkers that predict response to therapy would help to avoid unnecessary use of expensive biologics in non-responding patients and enable alternative treatments to be explored. Patient synovial-tissue samples from two clinical studies were analysed using Difference In-Gel Electrophoresis based proteomics to identify protein expression differences in response to anti-TNF-α treatment. Subsequent multiplexed multiple-reaction-monitoring (MRM) measurements were used to verify potential biomarkers. A total of 119 proteins were differentially expressed (p<0.05) in response to anti-TNF-α treatment and 25 proteins were differentially expressed (p<0.05) between "good responders" and "poor responders". From...