Publications by authors named "Ai-Lan Nguyen"

10 Publications

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Predicting Infection Risk in Multiple Sclerosis Patients Treated with Ocrelizumab: A Retrospective Cohort Study.

CNS Drugs 2021 Apr 13. Epub 2021 Apr 13.

Department of Neurology, Melbourne MS Centre, Royal Melbourne Hospital, Parkville, VIC, 3050, Australia.

Background: Ocrelizumab safety outcomes have been well evaluated in clinical trials and open-label extension (OLE) studies. However, risk factors for infection in patients with multiple sclerosis (MS) receiving ocrelizumab have not been extensively studied in the real-world setting.

Objective: The aim of this study was to examine factors determining risk of self-reported infections and antimicrobial use in patients receiving ocrelizumab for MS.

Methods: A retrospective, observational cohort study was conducted in patients receiving ocrelizumab at the Royal Melbourne Hospital. Infection type and number were reported by patients, and the associations of potential clinical and laboratory risk factors with self-reported infection and antimicrobial use were estimated using univariate and multivariable logistic regression models.

Results: A total of 185 patients were included in the study; a total of 176 infections were reported in 89 patients (46.1%), and antimicrobial use was identified in 47 patients (25.3%). In univariate analyses, a higher serum IgA was associated with reduced odds of infection (OR 0.44, 95% CI 0.25-0.76). In multivariable analyses, older age (OR 0.94, 95% CI 0.88-0.99), higher serum IgA (OR 0.37, 95% CI 0.17-0.80) and higher serum IgG (OR 0.81, 95% CI 0.67-0.99) were associated with reduced odds of infection. Older age (OR 0.85, 95% CI 0.75-0.96) and higher serum IgA (OR 0.23, 95% CI 0.07-0.79) were associated with reduced odds of antimicrobial use, whilst longer MS disease duration (OR 1.22, 95% CI 1.06-1.41) and higher Expanded Disability Status Scale (EDSS) score (OR 1.99, 95% CI 1.02-3.86) were associated with increased odds of antimicrobial use.

Conclusions: Higher serum IgA and IgG and older age were associated with reduced odds of infection. Our findings highlight that infection risk is not uniform in patients with MS receiving ocrelizumab and substantiate the need to monitor immunoglobulin levels pre-treatment and whilst on therapy.
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http://dx.doi.org/10.1007/s40263-021-00810-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042832PMC
April 2021

Fast and safe: Optimising multiple sclerosis infusions during COVID-19 pandemic.

Mult Scler Relat Disord 2021 Jan 1;47:102642. Epub 2020 Dec 1.

Alfred Health, Clinical Neurosciences, Melbourne, Australia; Department of Neuroscience, Central Clinical School, Monash University, Melbourne Australia.

Background: The COVID-19 pandemic challenges multiple sclerosis services to be innovative in delivering infusible therapies. To reduce time in clinical settings, and potential staff or space losses, we implemented rapid infusion protocols for selected patients.

Objective: To analyse the rate of infusion related reactions and patient experience of rapid infusions of natalizumab and ocrelizumab. To document time reduction patients spent in clinical settings during the COVID-19 pandemic.

Methods: Patients with prior exposure to at least three natalizumab or two 300mg ocrelizumab infusions were approved for rapid protocols. A retrospective audit and survey were completed.

Results: We analysed 269 rapid natalizumab infusions and 100 rapid ocrelizumab infusions. Infusion related reactions during the natalizumab or ocrelizumab infusions occurred in two patients (1.52%) and eight patients (8%), respectively. All infusion related reactions were mild to moderate and did not require infusion discontinuation. No infusion reactions occurred during the post-infusion observation. Patient experience was positive.

Conclusion: Frequency or severity of infusion related reactions in rapid infusions were no different compared to published data. In the setting of COVID-19, pandemic rapid infusion protocols could potentially save hospital resources and limit patient exposure to a high-risk clinical setting while still maintaining ongoing treatment of multiple sclerosis.
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http://dx.doi.org/10.1016/j.msard.2020.102642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955770PMC
January 2021

Evaluating the perspective of patients with MS and related conditions on their DMT in relation to the COVID-19 pandemic in one MS centre in Australia.

Mult Scler Relat Disord 2020 Nov 16;46:102516. Epub 2020 Sep 16.

Melbourne MS Centre, Department of Neurology, Royal Melbourne Hospital, Melbourne, Vic, Australia; Department of Neuroscience, Monash University, Melbourne, Vic, Australia; MS and Neuroimmunology Department, Alfred Health, Melbourne, Vic, Australia. Electronic address:

Objective: Patients with Multiple Sclerosis (MS) and on disease modifying therapies (DMTs) that can be immunosuppressive or immunomodulatory form a special group where risk of continuation of DMT needs to be taken into account with risk of contracting Covid-19. This concept can pose a degree of anxiety for patients as well as neurologists. We aimed to evaluate patient perspectives regarding the use of Natalizumab and anti-CD20 therapies (Rituximab and Ocrelizumab) in the context of the COVID-19 pandemic.

Methods: cross-sectional study conducted via voluntary survey filled in by patients with MS and related disorders receiving their infusional treatment in one MS centre in Australia, exploring their concerns regarding their therapy, their therapy and COVID-19, precautions undertaken in response to the pandemic, and factors impacting their decision-making.

Results: 170 patients completed the survey. Of patients on Natalizumab, the majority had either no or mild concern regarding their DMT and COVID-19, and of patients on B-cell depleting therapies, again, the majority had no or mild concern, though a slightly higher proportion had a moderate level of concern. Asked to delineate their concerns, an increased risk of contracting COVID-19 was more commonly conveyed than MS-specific factors or poor outcomes pertaining to COVID-19 if contracted, by patients in both groups. Conversely, being invited to specifically consider the possibility of contracting COVID-19 or experience a relapse of MS, almost half of the cohort rated both of equal of concern. More than half of the cohort were self-isolating more stringently than general government advice and government-related resources followed by information provided by patient's neurologist where the commonest means of information to guide decision making.

Conclusions: Whilst a large proportion of patients had some concern regarding the impact of their DMT on COVID-19, whether on their risk of contracting COVID-19 or a theoretical risk for more severe disease, the overall level of concern in most cases was at most mild. Patients on B-cell depleting therapies were more inclined to express a higher level of concern. A similar concern was ascribed to a risk of a relapse or worsening MS symptoms compared to the risk of contracting COVID-19. Such attitudes may underscore a willingness of patients to continue their DMT where benefits outweigh risks during future phases of the COVID-19 pandemic.
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http://dx.doi.org/10.1016/j.msard.2020.102516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493747PMC
November 2020

Association of Pregnancy With the Onset of Clinically Isolated Syndrome.

JAMA Neurol 2020 Sep 14. Epub 2020 Sep 14.

Department of Neurology, Alfred Hospital, Melbourne, Victoria, Australia.

Importance: Multiple sclerosis (MS) is usually diagnosed in women during their childbearing years. Currently, no consensus exists on whether pregnancy can delay the first episode of demyelination or clinically isolated syndrome (CIS).

Objective: To investigate the association of pregnancy with time to CIS onset.

Design, Setting, And Participants: This multicenter cohort study collected reproductive history (duration of each pregnancy, date of delivery, length of breastfeeding) on all participants between September 1, 2016, and June 25, 2019. Adult women being treated at the MS outpatient clinics of 4 tertiary hospitals in 2 countries (Charles University and General University Hospital in Prague, Czech Republic; Royal Melbourne Hospital in Melbourne, Australia; Alfred Hospital in Melbourne, Australia; and John Hunter Hospital in Newcastle, Australia) were recruited to participate in the study. Preexisting data (date of CIS onset, date of birth, sex, date of clinical onset, and Expanded Disability Status Scale result) were collected from MSBase, an international registry of long-term prospectively collected data on patients with MS. Data analyses were performed from June 1, 2019, to February 3, 2020.

Exposures: Gravida (defined as any pregnancy, including pregnancy that ended in miscarriage and induced abortion) and parity (defined as childbirth after gestational age of more than 20 weeks, including livebirth and stillbirth) before CIS onset.

Main Outcomes And Measures: Time to CIS onset. The following were assessed: (1) whether women with previous pregnancies and childbirths had a delayed onset of CIS compared with those who had never been pregnant and those who had never given birth, and (2) whether a dose response existed, whereby a higher number of gravidity and parity was associated with a later onset of CIS.

Results: Of the 2557 women included in the study, the mean (SD) age at CIS onset was 31.5 (9.7) years. Of these women, before CIS onset, 1188 (46%) had at least 1 pregnancy and 1100 (43%) had at least 1 childbirth. The mean (SD) age at first pregnancy was 23.3 (4.5) years and at first childbirth was 23.8 (4.5) years. Women with previous pregnancies and childbirths had a later onset of CIS compared with those who had never been pregnant (HR, 0.68; 95% CI, 0.62-0.75; P < .001), with a median delay of 3.3 (95% CI, 2.5-4.1) years. Women who had given birth also had a later CIS onset compared with women who had never given birth (HR 0.68; 95% CI, 0.61-0.75; P < .001), with a similar median delay of 3.4 (95% CI, 1.6-5.2) years. A higher gravidity and parity number was not associated with delay in CIS onset.

Conclusions And Relevance: This study suggests an association between previous pregnancies and childbirths and timing of CIS onset, but having more pregnancies or childbirths did not appear to be associated with a later CIS onset. Further studies are needed to help explain the mechanisms behind the associations between pregnancy and onset of multiple sclerosis.
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http://dx.doi.org/10.1001/jamaneurol.2020.3324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490748PMC
September 2020

Long-Term Stability of Neuroaxonal Structure in Alemtuzumab-Treated Relapsing-Remitting Multiple Sclerosis Patients.

J Neuroophthalmol 2020 03;40(1):37-43

Department of Medicine (Neurology) (JKC, VD, A-LS, RC, AT), University of British Columbia, Vancouver, Canada; Department of Neurology (EHMdL, SA-A), Center of Neuroimmunology, Hospital Clinic of Barcelona, Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; Department of Statistics (CT), University of British Columbia, Vancouver, Canada; Department of Neruology (A-LN), University of Melbourne, Melbourne, Australia; Royal Melbourne Hospital (A-LN), Melbourne, Australia; and Departments of Clinical Neurosciences and Surgery (Ophthalmology) (FC), University of Calgary, Clinician Scientist with the Hotchkiss Brain Institute (HBI), Calgary, Canada.

Background: Patients with multiple sclerosis (MS) experience progressive thinning in optical coherence tomography (OCT) measures of neuroaxonal structure regardless of optic neuritis history. Few prospective studies have investigated the effects of disease-modifying therapies on neuroaxonal degeneration in the retina. Alemtuzumab is a monoclonal antibody shown to be superior to interferon β-1a in treating relapsing-remitting MS (RRMS). The purpose of this study was to assess the effects of alemtuzumab and first-line injectable treatments on OCT measures of neuroaxonal structure including peripapillary retinal nerve fiber layer (RNFL) thickness and combined ganglion cell-inner plexiform (GCIP) layer volume in RRMS patients followed up over 5 years.

Methods: In this retrospective pilot study with prospectively collected double cohort data, spectral domain OCT measures of RNFL thickness and GCIP volume were compared between alemtuzumab-treated RRMS patients (N = 24) and RRMS patients treated with either interferon-β or glatiramer acetate (N = 21).

Results: Over a median of 60 months (range 42-60 months), the alemtuzumab cohort demonstrated a change in the mean RNFL thickness (thinning from baseline) of -0.88 μm (95% confidence interval [CI] -2.63 to 0.86; P = 0.32) and mean GCIP volume of +0.013 mm (95% CI -0.006 to 0.032; P = 0.18). Over the same time period, the first-line therapy-treated cohort demonstrated greater degrees of RNFL thinning (mean change in RNFL thickness was -3.65 μm [95% CI -5.40 to -1.89; P = 0.0001]). There was also more prominent GCIP volume loss relative to baseline in the first-line therapy group (-0.052 mm [95% CI -0.070 to -0.034; P < 0.0001]).

Conclusions: Alemtuzumab-treated patients with RRMS demonstrated relative stability of OCT-measured neuroaxonal structure compared with RRMS patients treated with either interferon-β or glatiramer acetate over a 5-year period. These findings, along with previous demonstration of improved brain atrophy rates, suggest that alemtuzumab may offer long-term preservation of neuroaxonal structure in patients with RRMS.
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http://dx.doi.org/10.1097/WNO.0000000000000802DOI Listing
March 2020

Pregnancy and multiple sclerosis: Clinical effects across the lifespan.

Autoimmun Rev 2019 Oct 8;18(10):102360. Epub 2019 Aug 8.

Department of Medicine, University of Melbourne, Parkville, Australia; Department of Neurology, Royal Melbourne Hospital, Parkville, Australia; Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia; Department of Neurology, MSNI Service, Alfred Health, Melbourne, Australia.

Multiple sclerosis (MS) is commonly diagnosed in women of childbearing age. Having a greater understanding of the effects of pregnancy on the course of MS will lead to improved family-planning counselling for women. We found well-established evidence for a protective effect of pregnancy on relapse occurrence in historical cohorts. More recent studies suggest that the protective effect of pregnancy against relapse may be lost in those women with more active disease treated with high efficacy therapies. Furthermore, a strong body of evidence suggests that gravidity after diagnosis of MS does not lead to worse long-term outcomes. More contentious however, is whether pregnancy can delay a first episode of demyelination or a confirmed diagnosis of MS. This review provides a detailed analysis of the literature relating to the clinical effects of pregnancy on MS outcomes across a woman's reproductive lifespan.
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http://dx.doi.org/10.1016/j.autrev.2019.102360DOI Listing
October 2019

Family planning, antenatal and post partum care in multiple sclerosis: a review and update.

Med J Aust 2019 09 27;211(5):230-236. Epub 2019 Mar 27.

Monash University, Melbourne, VIC.

Multiple sclerosis is more prevalent in women of childbearing age than in any other group. As a result, the impact of multiple sclerosis and its treatment on fertility, planned and unplanned pregnancies, post partum care and breastfeeding presents unique challenges that need to be addressed in everyday clinical practice. Given the increasing number of disease-modifying agents now available in Australia for the treatment of multiple sclerosis, there is a growing need for clinicians to provide their patients with appropriate counselling on family planning. Providing better evidence regarding the relative risks and benefits of continuing therapy before, during and after pregnancy is an important research priority. International pregnancy registries are essential in developing better evidence-based practice guidelines, and neurologists should be encouraged to contribute to these when possible. The management of women with multiple sclerosis, especially when they are taking disease-modifying agents, requires careful assessment of fertility and disease characteristics as well as a multidisciplinary approach to ensure positive outcomes in both mothers and their children.
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http://dx.doi.org/10.5694/mja2.50113DOI Listing
September 2019

Incidence of pregnancy and disease-modifying therapy exposure trends in women with multiple sclerosis: A contemporary cohort study.

Mult Scler Relat Disord 2019 Feb 3;28:235-243. Epub 2019 Jan 3.

Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia; Department of Neurology, Alfred Hospital, Melbourne, Australia; Department of Medicine (Royal Melbourne Hospital), University of Melbourne, Melbourne, Australia. Electronic address:

Background: Exposure to disease-modifying therapy (DMT) during early pregnancy in women with relapsing-remitting MS (RRMS) may be increasing.

Objective: To retrospectively determine incidence of pregnancy, DMT exposure and pregnancy outcomes in women with RRMS.

Methods: We identified all women with RRMS aged 15-45 years in the MSBase Registry between 2005-2016. Annualised pregnancy incidence rates were calculated using Poisson regression models. DMT exposures and pregnancy outcomes were assessed.

Results: Of 9,098 women meeting inclusion criteria, 1,178 (13%) women recorded 1,521 pregnancies. The annualised incidence rate of pregnancy was 0.042 (95% CI 0.040, 0.045). A total of 635 (42%) reported pregnancies were conceived on DMT, increasing from 27% in 2006 to 62% in 2016. The median duration of DMT exposure during pregnancy was 30 days (IQR: 9, 50). There were a higher number of induced abortions on FDA pregnancy class C/D drugs compared with pregnancy class B and no DMT (p = 0.010); but no differences in spontaneous abortions, term or preterm births.

Conclusions: We report low pregnancy incidence rates, with increasing number of pregnancies conceived on DMT over the past 12-years. The median duration of DMT exposure in pregnancy was relatively short at one month.
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http://dx.doi.org/10.1016/j.msard.2019.01.003DOI Listing
February 2019

Validation of a precision tremor measurement system for multiple sclerosis.

J Neurosci Methods 2019 01 19;311:377-384. Epub 2018 Sep 19.

The Bionics Institute, East Melbourne, Australia; Department of Neurology, Royal Melbourne Hospital, Australia; Department of Neuroscience, Central Clinical School, Monash University, Victoria, Australia.

Background: Tremor is a debilitating symptom of Multiple Sclerosis (MS). Little is known about its pathophysiology and treatments are limited. Clinical trials investigating new interventions often rely on subjective clinical rating scales to provide supporting evidence of efficacy.

New Method: We present a novel instrument (TREMBAL) which uses electromagnetic motion capture technology to quantify MS tremor. We aim to validate TREMBAL by comparison to clinical ratings using regression modelling with 310 samples of tremor captured from 13 MS participants who performed five different hand exercises during several follow-up visits. Minimum detectable change (MDC) and test-retest reliability were calculated and comparisons were made between MS tremor and data from 12 healthy volunteers.

Results: Velocity of the index finger was most congruent with clinical observation. Regression modelling combining different features, sensor configurations, and labelling exercises did not improve results. TREMBAL MDC was 84% of its initial measurement compared to 91% for the clinical rating. Intra-class correlations for test-retest reliability were 0.781 for TREMBAL and 0.703 for clinical ratings. Tremor was lower (p =  0.002) in healthy subjects.

Comparison With Existing Methods: Subjective scales have low sensitivity, suffer from ceiling effects, and mitigation against inter-rater variability is challenging. Inertial sensors are ubiquitous, however, their output is nonlinearly related to tremor frequency, compensation is required for gravitational artefacts, and their raw data cannot be intuitively comprehended.

Conclusions: TREMBAL, compared with clinical ratings, gave measures in agreement with clinical observation, had marginally lower MDC, and similar test-retest reliability.
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http://dx.doi.org/10.1016/j.jneumeth.2018.09.022DOI Listing
January 2019

Monoclonal antibodies in the treatment of multiple sclerosis: emergence of B-cell-targeted therapies.

Br J Pharmacol 2017 07 26;174(13):1895-1907. Epub 2017 Apr 26.

Multiple Sclerosis Division, The Florey Institute of Neuroscience and Mental Health, Parkville, Vic., Australia.

Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS, and one of the most common causes of disability in young adults. Over the last decade, new disease-modifying therapies have emerged, including monoclonal antibodies (mAbs) that provide highly targeted therapies with greater efficacy than platform therapies. In particular, monoclonal antibodies directed against CD20-positive B cells have shown remarkable results in recent clinical trials and renewed interest in the mechanism of B cell-depleting therapies to ameliorate relapse activity and progression in MS. Here, we review the mechanisms of action and clinical evidence of approved and emerging mAbs, with a focus on B cell-targeted therapies.
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http://dx.doi.org/10.1111/bph.13780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5466523PMC
July 2017