Allan G Kermode

Background
Patients aged ≥35 years at multiple sclerosis (MS) onset with an Expanded Disability Status Scale (EDSS) ≥3 in the first year are at highest risk of aggressive MS (EDSS ≥6 within 10 years). Those without these features are at lowest risk. We aimed to assess whether high-efficacy therapy improves outcomes in high-risk patients and whether its benefit varies by MS severity.

Methods
This longitudinal cohort study analysed MSBase and OFSEP registry data. Patients were categorized into high- or low-risk of aggressive MS. Within each risk strata, relapse and disability accumulation were compared between those receiving high-efficacy therapy (fingolimod, cladribine, monoclonal antibodies) vs. other/no therapy. Marginal structural models, adjusting for demographics, MS course, relapses, disability, and MRI activity, were used to evaluate treatment effects and interaction with aggressive MS risk.

Results
4560 patients (893 high risk, 3667 low risk) were studied. Continuous treatment with high-efficacy therapy vs other/no therapy reduced the risk of relapse and disability accumulation in patients at both high-risk and low-risk of aggressive MS.There was no evidence of an interaction between aggressive MS risk and treatment strategy. The risk of relapse was lowest in patients at low-risk of aggressive MS treated with high-efficacy therapy (HR0.58, 95%CI 0.54–0.62). High-efficacy therapy reduced the risk of disability accumulation across both aggressive MS risk strata.

Conclusion
High-efficacy therapy reduces relapse and disability accumulation in patients at both high- and low-risk of aggressive MS, with no differential treatment benefit. These findings support widespread use of high-efficacy therapy in relapsing MS.

Background/Objective
Cognitive fatigability (CF) affects many with Multiple Sclerosis (MS), yet measurement remains challenging due to poor correlation with subjective fatigue reports. MSReactor cognitive screening platform offers potential for objective CF assessment, particularly for longitudinal monitoring in clinical settings.

Objective
To determine whether changes in error rates during sustained cognitive testing provide a platform for studies investigating CF and its relationship to disease progression.

Methods
Adults with relapsing-remitting and secondary-progressive MS were recruited from seven Australian tertiary MS clinics. Participants completed MSReactor cognitive testing battery: a simple reaction time, a choice reaction time, and a One back test (OBK, which is a measure of working memory). Each test required participants to make 32–35 responses to stimuli appearing on screen. CF was quantified as a sustained doubling of incorrect responses in the last third compared to first third of OBK test. Expanded Disability Status Scale (EDSS) was assessed as part of standard care.

Results
Among 836 participants, 113 (13.5%) demonstrated a sustained doubling of errors in OBK task over follow-up period (median 890 days, IQR: 1070). Of these, 7 participants with sustained increases in intra-test error rates subsequently had a 6-month confirmed disability progression event.

Conclusion
This study explores MSReactor as an objective measure of CF in MS. We identified a group of participants who consistently made more errors in latter third of a sustained working memory test, which appeared independent of future disability progression. Further research is needed to validate this finding against clinical correlates and work productivity.

Background
Managing multiple sclerosis (MS) in cancer survivors is complex due to immune system interactions and the impact of treatment. Limited guidance exists on disease-modifying therapy (DMT) use during and after chemotherapy. This study examined how DMT decisions in breast cancer influence MS outcomes and whether chemotherapy itself affects MS disease activity.

Methods
Data were obtained from the MSBase registry, including 172 individuals with MS and breast cancer who received chemotherapy, and 229 for whom chemotherapy data were not available. Survival analyses assessed time to first relapse and confirmed disability progression (CDP) after cancer diagnosis, with DMT modelled as a time-varying covariate. Propensity score matching compared outcomes between those who received cancer chemotherapy adjuvant to their MS treatment and matched controls receiving standard MS treatment alone.

Results
Post-chemotherapy MS management varied, with most clinicians de-escalating or withholding DMTs. Older age was associated with lower relapse risk (HR = 0.90, 95% CI: 0.93–0.97, p = 0.001). Chemotherapy had a protective effect on time to first relapse (HR 0.58, 95% robust CI: 0.37 to 0.95, p = 0.03) compared to matched controls receiving standard MS treatment. Chemotherapy was not associated with a significant effect on CDP (HR 0.68, 95% robust CI: 0.38–1.23, p=0.06).

Conclusion
Chemotherapy was associated with better relapse outcomes compared to standard therapy in matched controls, supporting withholding or de-escalating DMTs during cancer treatment. DMT reinitiation should be guided by individual risk assessment and may be less indicated in older individuals, who demonstrated a lower relapse risk following chemotherapy.

Objectives
RRMS is an immune-mediated, demyelinating condition often treated with the monoclonal antibody natalizumab. The administration of this intravenous infusion 4 weekly and the potential for adverse events poses a great inconvenience to patients requiring them to attend hospital day-units to receive treatment. We aimed to establish a safe, patient centric home infusion service for patients being treated with natalizumab as monotherapy for RRMS. Establishment of the home infusion service addressed regulatory requirements, risk minimisation strategies for known toxicities, occupational health and safety concerns and medication management, including storage and transport.

Methods
An accredited, hospital substitute service (chemo@home) developed a protocol for the administration of natalizumab at home. The protocol was approved by the health services Expert Reference Group (Neurology) and Medication Advisory Group. Medical governance is retained by the neurologist. All health professionals (medical, nursing and pharmacy) complete the relevant sections of the Tysabri Australian prescribing program (TAPP). JC virus seronegative patients are monitored 6 monthly for seroconversion. Resources for the management of adverse reactions (including resuscitation equipment/medications) are available. All pre-infusion regulatory and clinical requirements are fulfilled. Natalizumab infusions are prepared, using a closed system, and administered in the patient’s home by registered nurses. Patient questionnaires on the experience were collected.

Results
Between February 2014 and January 2017, 34 patients received 494 doses of natalizumab at home. A median of 11 (range 1–37). infusions were given. There were no episodes of anaphylaxis, hypersensitivity, unexpected toxicities and no additional safety concerns identified. Patient satisfaction was high. The at-home service made treatment significantly easier and less stressful than in hospital.

Conclusions
To our knowledge this is the first establishment of an accredited, hospital-substitute service (chemo@home) in Australia which gives RRMS patients access to natalizumab treatment at home. It was achieved without compromising safety and with a high level of patient satisfaction.