Background In Australia, tixagevimab/cilgavimab 150 mg/150 mg was a government-funded pre-exposure prophylaxis for COVID-19 people with multiple sclerosis (pwMS) and other neuroimmunological conditions (pwNIc) treated with anti-CD20 antibodies or sphingosine-1-phosphate receptor modulators were eligible. Objective To analyse the roll-out, uptake and real-world efficacy of tixagevimab/cilgavimab in the prevention and severity of COVID-19. To assess compliance with uptake depending on the location of delivery. Methods We undertook a single-centre study. 440 pwMS and pwNIc were eligible. Logistic regression was used to assess predictors of COVID-19 during follow-up and to assess predictors of uptake among those who consented. Results Of the eligible pwMS and pwNIc in our service, 52.7% (233/440) requested a consultation and were included in this study. Consultation resulted in 71.7% of people (167/233) receiving the treatment. Of these, 94.0% (157/167) had received three or more COVID-19 vaccines. Among those who received a single dose of tixagevimab/cilgavimab, 19.16% (32/167) tested positive for COVID-19 during the observational window. The majority of these were on ocrelizumab (68.8% (22/32)). None of those with COVID-19 required hospitalisation or supplemental oxygen. There was no difference in odds of COVID-19 during the observation period between those who received and did not receive tixagevimab/cilgavimab (adjusted OR, aOR 2.16 (95% CI 0.82 to 6.85), p=0.43). Uptake of tixagevimab/cilgavimab was highest when offered at the hospital infusion centre (aOR 3.09 (95% CI 1.08 to 9.94) relative to referral to the local pharmacy, p=0.04). Conclusion Tixagevimab/cilgavimab administration did not protect against subsequent COVID-19 in our cohort. Compliance with uptake was influenced by administration location.
Background: Increasingly, people with relapsing-remitting multiple sclerosis (RRMS) are switched to highly effective disease-modifying therapies (DMTs) such as ocrelizumab. Objective: To determine predictors of relapse and disability progression when switching from another DMT to ocrelizumab. Methods: Patients with RRMS who switched to ocrelizumab were identified from the MSBase Registry and grouped by prior disease-modifying therapy (pDMT; interferon-β/glatiramer acetate, dimethyl fumarate, teriflunomide, fingolimod or natalizumab) and washout duration (<1 month, 1–2 months or 2–6 months). Survival analyses including multivariable Cox proportional hazard regression models were used to identify predictors of on-ocrelizumab relapse within 1 year, and 6-month confirmed disability progression (CDP). Results: After adjustment, relapse hazard when switching from fingolimod was greater than other pDMTs, but only in the first 3 months of ocrelizumab therapy (hazard ratio (HR) = 3.98, 95% confidence interval (CI) = 1.57–11.11, p = 0.004). The adjusted hazard for CDP was significantly higher with longer washout (2–6 m compared to <1 m: HR = 9.57, 95% CI = 1.92–47.64, p = 0.006). Conclusion: The risk of disability worsening during switch to ocrelizumab is reduced by short treatment gaps. Patients who cease fingolimod are at heightened relapse risk in the first 3 months on ocrelizumab. Prospective evaluation of strategies such as washout reduction may help optimise this switch.
Existing instruments for caregiver burden assessment are not specific or sensitive to various aspects of caring for patients with Parkinson's disease. A better understanding of burden may enhance patient care and improve health of both patient and caregiver. The goal of this study was to evaluate the validity of the Parkinson's Disease Caregiver Burden (PDCB) questionnaire, a novel instrument designed to appraise more accurately the burden experienced by caregivers in the setting of Parkinson's disease.Common sources of distress for caregivers were taken from discussions with Parkinson's disease patients, caregivers, and clinicians, and used as the foundation of the PDCB questionnaire items. Fifty patients and their respective caregivers were recruited from three specialist movement disorder clinics. Caregiver burden in the sample was gauged with the PDCB scale and the Caregiver Burden Inventory (CBI). Item sensitivity and questionnaire validity were assessed.In this pilot analysis, the PDCB questionnaire was found to be feasible and reliable. Strong correlations were found between the PDCB questionnaire and the CBI. The PDCB questionnaire contained more relevant items for this population compared with the CBI.Strong initial feasibility, reliability, validity, and sensitivity for the PDCB questionnaire were demonstrated. With further evaluation and development, the PDCB questionnaire may prove to be a valuable supplementary tool to the existing CBI or a standalone instrument for use in the setting of Parkinson's disease.
Abstract
Background: People with multiple sclerosis and neuroimmunologic disorders (herein referred to as patients) are increasingly treated with infusible monoclonal antibodies. This rise in demand has placed increased loads on current infusion services and mandates careful strategic planning. This study examined patient preferences for the timing and location of infusions and their association with demographic and disease variables to facilitate patient-focused strategic planning.
Methods: Ninety-one patients receiving an infusible therapy at an infusion service during March 2019 were asked to complete a questionnaire exploring eight domains, including preferences for time of infusions and location of infusion centers. Potential access to home-based treatment was included as an option. Unstructured (free-text) feedback on current service was also obtained.
Results: Eighty-three patients completed the survey (mean age, 42 years; 75% women). Infusions were predominantly natalizumab (66%) and ocrelizumab (25%). Of these patients, 71% were engaged in some form of work or study, and 83% of this group had to arrange time off from work or study to attend treatment. Seventy percent of patients would prefer their infusion before noon, and 60% would consider home-based infusions. Most used a car as their transport to the infusion service.
Conclusions: These results suggest that patients are more likely to prefer infusible treatment in the morning and are open to home-based infusions. This study provides information for health services to target service delivery at peak preference times and consider alternate ways of delivering infusible treatments.
Multiple sclerosis (MS) is a chronic inflammatory demyelinating and degenerative disease of the central nervous system. There were 33 335 people with MS in Australia in 2021 and 2917 in New Zealand in 2006 and the prevalence and incidence are increasing with time. Although new treatments have substantially improved outcomes in recent decades, the treatment landscape has become increasingly complex due to the expanding number of disease-modifying therapies (DMTs) and associated safety considerations. A total of 80 consensus recommendations were developed on the current best-practice management of MS in Australia and New Zealand. Part 1 of these guidelines outlines the consensus recommendations covering domains including DMT counselling and selection, pre-DMT assessments, monitoring disease activity on DMT, switching DMT, and discontinuing DMT. The remaining recommendations are outlined in Part 2, encompassing risk mitigation strategies during treatment with DMT, managing DMT in special situations (including pregnancy, postpartum, breastfeeding, active infection including COVID-19, and malignancy), general lifestyle measures, acute MS relapses, and symptomatic treatments for MS. This two-part position statement provides a practical resource for clinicians on current best-practice consensus recommendations for managing adults (≥ 18 years old) with MS in the Australian and New Zealand health care settings. It outlines the 14 DMTs currently available through the Australian Pharmaceutical Benefits Scheme and eight through the New Zealand Pharmaceutical Schedule, including the unique efficacy, safety and monitoring considerations of each. Through these guidelines, we aim to support safe, timely and effective management of patients with MS in Australia and New Zealand.
Background Ongoing controversy exists regarding optimal management of disease modifying therapy (DMT) in older people with multiple sclerosis (pwMS). There is concern that the lower relapse rate, combined with a higher risk of DMT-related infections and side effects, may alter the risk-benefit balance in older pwMS. Given the lack of pwMS above age 60 in randomised controlled trials, the comparative efficacy of high-efficacy DMTs such as ocrelizumab has not been shown in older pwMS. We aimed to evaluate the comparative effectiveness of ocrelizumab, a high-efficacy DMT, versus interferon/glatiramer acetate (IFN/GA) in pwMS over the age of 60. Methods Using data from MSBase registry, this multicentre cohort study included pwMS above 60 who switched to or started on ocrelizumab or IFN/GA. We analysed relapse and disability outcomes after balancing covariates using an inverse probability treatment weighting (IPTW) method. Propensity scores were obtained based on age, country, disease duration, sex, baseline Expanded Disability Status Scale, prior relapses (all-time, 12 months and 24 months) and prior DMT exposure (overall number and high-efficacy DMTs). After weighting, all covariates were balanced. Primary outcomes were time to first relapse and annualised relapse rate (ARR). Secondary outcomes were 6-month confirmed disability progression (CDP) and confirmed disability improvement (CDI). Results A total of 248 participants received ocrelizumab, while 427 received IFN/GA. The IPTW-weighted ARR for ocrelizumab was 0.01 and 0.08 for IFN/GA. The IPTW-weighted ARR ratio was 0.15 (95% CI 0.06 to 0.33, p<0.001) for ocrelizumab compared with IFN/GA. On IPTW-weighted Cox regression models, HR for time to first relapse was 0.13 (95% CI 0.05 to 0.26, p<0.001). The hazard of first relapse was significantly reduced in ocrelizumab users after 5 months compared with IFN/GA users. However, the two groups did not differ in CDP or CDI over 3.57 years. Conclusion In older pwMS, ocrelizumab effectively reduced relapses compared with IFN/GA. Overall relapse activity was low. This study adds valuable real-world data for informed DMT decision making with older pwMS. Our study also confirms that there is a treatment benefit in older people with MS, given the existence of a clear differential treatment effect between ocrelizumab and IFN/GA in the over 60 age group.
In Australia, Evusheld – (tixagevimab150mg and cilgavimab150mg) is currently the only pre-exposure prophylaxis for COVID-19 infection Persons with Multiple Sclerosis (pwMS) who are treated with anti-CD20 antibodies and sphingosine 1- phosphate receptor modulators have an impaired vaccine-induced immune response, resulting in an increased risk of severe COVID-19 infection. The uptake and efficacy of Evusheld in real-world MS populations is not known and forms the basis of this study.
Objective
To analyse the uptake, compliance, and real-world efficacy of Evusheld in prevention and severity of COVID 19 infections.
Methods
This study was approved by Human Research Ethics Committee (HREC) and was conducted in a tertiary MS centre. We retrospectively analysed electronic medical records (EMR) and MSBase registry of pwMS with documented prior patient driven consultation to discuss Evusheld. Follow up phone call to confirm administration and any COVID 19 infection was undertaken by two nursing staff.
Results
Of the eligible pwMS in our service only 52.7% requested a formal consultation to discuss Evusheld. A total of 233 pwMS were included in the study. Evusheld consultation resulted in 71.67% Evusheld administration. 94.1% of pwMS who received Evusheld had already has three or more COVID 19 vaccines. 19.16% of those who had received a single dose of Evusheld later tested positive for COVID 19 during the 26 weeks observation period. The majority of these individual (68.8%) were on Ocrelizumab. Nil required hospitalisation. Administration site setting was more favourable at opportunistic infusion centre.
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.
Ocrelizumab is an anti-CD20 monoclonal antibody (mAb) that has been shown in phase 3 clinical trials to reduce relapses and disease progression in multiple sclerosis (MS) patients. Prior to the approval of ocrelizumab, rituximab, a chimeric anti-CD20 mAb was used to treat MS. Rituximab is still used to treat MS in many countries outside of Australia and remains mainstay of treatment of many non-MS neuroimmunological and systemic inflammatory diseases. Rituximab is currently used in neuromyelitis optica spectrum disorder (NMOSD) and autoimmune encephalitis, in addition to its widespread usage in hematological malignancies and systemic inflammatory diseases. Ocrelizumab is currently approved in Australia for treatment of relapsing-remitting MS (RRMS). Neutropaenia is a rare complication of both ocrelizumab and rituximab treatment. This case series reports 12 patients who have experienced neutropaenia following ocrelizumab or rituximab treatment and aims to characterize the clinical parameters of neutropaenia experienced by these patients, including the severity and duration of neutropaenia, length of hospital admission, the types of subsequent infections experienced and types of treatment necessary before patients reached count recovery. The unpredictability of neutropaenia and potential for serious infections highlight the need for continued hematological monitoring for patients on B-cell depleting therapies and calls for careful patient counselling to provide guidance on whether to continue such therapies in patients who have experienced related neutropaenia.
Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system with rapidly evolving treatment options and strategies. An iterative modified Delphi process was used to develop 80 consensus recommendations for the management of MS in Australia and New Zealand. Part 1 of these guidelines includes recommendations related to selection of initial disease-modifying therapy (DMT) for MS, assessments before commencing DMT, monitoring disease activity on DMT, switching DMT, and discontinuing DMT. This article, Part 2, covers recommendations related to risk mitigation during treatment with DMT, managing DMT in special situations (including pregnancy, postpartum, breastfeeding, active infection including COVID-19, and malignancy), general lifestyle measures for MS, acute MS relapses, and symptomatic treatments. Together with Part 1, this consensus statement provides practical guidance for clinicians involved in the care of adults (≥ 18 years old) with MS in Australia and New Zealand. A safe, effective and comprehensive approach to managing MS is crucial for improving long term outcomes and quality of life in individuals affected by MS.
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