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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.

Aims: To retrospectively assess factors associated with John Cunningham virus (JCV) seroconversion in natalizumab-treated patients. Background: Natalizumab is highly effective for the treatment of relapsing–remitting multiple sclerosis (RRMS), but its use is complicated by opportunistic JCV infection. This virus can result in progressive multifocal leukoencephalopathy (PML). Serial assessment of JCV serostatus is mandated during natalizumab treatment. Methods: Patients treated with natalizumab for RRMS at six tertiary hospitals in Melbourne, Australia ( n = 865) and 11 MS treatment centres in Brazil ( n = 136) were assessed for change in JCV serostatus, duration of exposure to natalizumab and prior immunosuppression. Sensitivity analyses examined whether sex, age, tertiary centre, prior immunosuppression or number of JCV tests affected time to seroconversion. Results: From a cohort of 1001 natalizumab-treated patients, durable positive seroconversion was observed in 83 of 345 initially JCV negative patients (24.1%; 7.3% per year). Conversely, 16 of 165 initially JCV positive patients experienced durable negative seroconversion (9.7%; 3.8% per year). Forty patients (3.9%) had fluctuating serostatus. Time-to-event analysis did not identify a relationship between JCV seroconversion and duration of natalizumab exposure. Prior exposure to immunosuppression was not associated with an increased hazard of positive JCV seroconversion. Male sex was associated with increased JCV seroconversion risk [adjusted hazard ratio 2.09 (95% confidence interval 1.17–3.71) p = 0.012]. Conclusion: In this large international cohort of natalizumab-treated patients we observed an annual durable positive seroconversion rate of 7.3%. This rate exceeds that noted in registration and post-marketing studies for natalizumab. This rate also greatly exceeds that predicted by epidemiological studies of JCV seroconversion in healthy populations. Taken together, our findings support emerging evidence that natalizumab causes off-target immune changes that may be trophic for JCV seroconversion. In addition, male sex may be associated with increased positive JCV seroconversion.

Background: family planning and pregnancy decisions are key considerations in the management of women with multiple sclerosis (MS), who are typically diagnosed between the ages of 20–40 years. Despite a strong evidence base that pregnancy is not harmful for women with MS, many knowledge gaps remain. These include: best management strategies through pregnancy in the era of highly effective disease-modifying therapies (DMT); foetal risks associated with DMT exposure in utero or in relation to breastfeeding; knowledge base around the use of assisted reproductive technologies; the long-term impact of pregnancy on disease outcomes, as well as the impact of long-term DMT use on women’s health and cancer risk. Methods: here, we describe the new MSBase pregnancy, neonatal outcomes and women’s health registry. We provide the rationale for, and detailed description of, the variables collected within the registry, together with data acquisition details. Conclusion: the present paper will act as a reference document for future studies., National Health and Medical Research Council of Australia; MSBase Foundation; Roche; Merck; Biogen; Novartis; Bayer-Schering; Sanofi Genzyme; Teva

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

Background Natalizumab, a monoclonal antibody directed against α4 integrin, is a highly efficacious treatment commonly used in relapsing remitting multiple sclerosis. Natalizumab is associated with the potentially fatal, rare, demyelinating, opportunistic brain infection, progressive multifocal leukoencephalopathy (PML). Prognosis and disability from PML are determined by early diagnosis. Aims Written tools are mandated in Australia and other prescribing countries with the aim to help patients understand the risks associated with treatment and ensure familiarity with the early symptoms of PML. We aimed to assess if these tools achieve such an outcome. Methods A cross-sectional survey was conducted using a convenience sample of multiple sclerosis patients prescribed natalizumab presenting to the infusion centre at a major tertiary hospital. Patients were offered a multi-choice questionnaire to assess their knowledge on the treatment risks and surveillance requirements of their therapy. Three specific questions were highlighted by the researchers as crucial to patient understanding of PML and defined as basic knowledge. Results A total of 48 patients in our hospital was prescribed natalizumab; 37 responded. A total of 16 (43.2%) patients answered all three basic knowledge questions correctly. There was no difference in the ability to answer these questions based on length of treatment or co-ownership knowledge between patients with base knowledge and without. Conclusion Natalizumab is associated with an increased risk of PML. Early detection and treatment of PML results in improved patient outcomes. Patient knowledge and co-partnership in the utilisation of PML risk tools is relevant in ensuring early detection. Our findings question the ability of currently sanctioned tools to inform patients of basic knowledge of PML and their risk of developing PML. A future study with a repetitive education approach and repeating the questionnaire at multiple time points would be of interest.

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.

CME/CNE Information Activity Available Online: To access the article, post-test, and evaluation online, go to http://www.cmscscholar.org. Target Audience: The target audience for this activity is physicians, physician assistants, nursing professionals, and other health-care providers involved in the management of patients with multiple sclerosis (MS). Learning Objectives: Accreditation Statement: This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of the Consortium of Multiple Sclerosis Centers (CMSC), Nurse Practitioner Alternatives (NPA), and Delaware Media Group. The CMSC is accredited by the ACCME to provide continuing medical education for physicians. The CMSC designates this journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Nurse Practitioner Alternatives (NPA) is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's Commission on Accreditation. NPA designates this enduring material for 1.0 Continuing Nursing Education credit (1.0 in the area of pharmacology). Laurie Scudder, DNP, NP, has served as Nurse Planner and reviewer for this activity. She has disclosed no relevant financial relationships. Disclosures: Editor in Chief of the International Journal of MS Care (IJMSC), has served as Physician Planner for this activity. He has received royalties from Springer Publishing, received intellectual property rights/patent holder from Biogen, and has performed contracted research for Biogen.Francois Bethoux, MD, has served as Nurse Planner and reviewer for this activity. She has disclosed no relevant financial relationships.Laurie Scudder, DNP, NP, has received a travel grant from Genzyme.Louise Rath, MA (Bioethics), Grad Dip Crit Care, BA, RN, , has disclosed no relevant financial relationships.Nirosen Vijiaratnam, MBBS, BMedSci , has served on a speakers' bureau for and received a travel grant from Genzyme.Olga Skibina, MD, FRACP The anonymous peer reviewers for the IJMSC have disclosed no relevant financial relationships. The staff at the IJMSC, CMSC, NPA, and Delaware Media Group who are in a position to influence content have disclosed no relevant financial relationships. Note: Disclosures listed for authors are those applicable at the time of their work on this project and within 12 months previously. Financial relationships for some authors may have changed in the interval between the time of their work on this project and publication of the article and/or the authors may list other older disclosures at the end of the article. Method of Participation: Release Date: December 1, 2017 Valid for Credit Through: December 1, 2018 In order to receive CME/CNE credit, participants must: Statements of Credit are awarded upon successful completion of the post-test with a passing score of >70% and the evaluation. There is no fee to participate in this activity. Disclosure of Unlabeled Use: This CME/CNE activity may contain discussion of published and/or investigational uses of agents that are not approved by the FDA. CMSC, NPA, and Delaware Media Group do not recommend the use of any agent outside of the labeled indications. The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of CMSC, NPA, or Delaware Media Group. Disclaimer: Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any medications, diagnostic procedures, or treatments discussed in this publication should not be used by clinicians or other health-care professionals without first evaluating their patients' conditions, considering possible contraindications or risks, reviewing any applicable manufacturer's product information, and comparing any therapeutic approach with the recommendations of other authorities.

IntroductionLong-term exposure of women with Multiple sclerosis (MS, wwMS) to immunomodulatory or immunosuppressive treatments may increase the risk of cervical dysplasia. However, little is known about cervical dysplasia risk and Human Papillomavirus (HPV)-vaccine coverage in wwMS.MethodsAdult wwMS were recruited from two tertiary MS clinics. To explore the association between MS treatments (DMTs) and abnormal cervical screening tests (CSTs), we linked individual data from MSBase, the Victorian Cervical Screening Registry, and National HPV vaccination program registry (NHPVPR).ResultsTo date, we have recruited 208 wwMS of whom 102 had complete data (vaccination status, cervical screening tests, MSBase data) and no previous history of abnormal CST at MS onset for this interim analysis. The average age was 33.8 (18 to 59 yrs) and most (n=58, 88%) were unvaccinated. 19 wwMS (19%) had an abnormal CST after MS onset (incidence rate 20.6 cases/1000 person-years, 95% confidence interval 12.4–32.1) over average 9.0 years of follow-up. 57 wwMS were treated with lower-efficacy therapies (56%), 73 with a high-efficacy therapy (72%), and 44 were exposed to both. Eight abnormal CSTs were detected before starting high-efficacy therapy (rate 12.6, 95% CI (5.4–24.8)) and 11 were detected after starting high-efficacy therapy (rate 38.6, 95% CI (19.3–69.0), p=0.022.ConclusionWe provide preliminary data that high efficacy DMTs may increase the risk of abnormal CSTs over time. A larger cohort and inclusion of additional cervical dysplasia risk factors are required to fully elucidate risk in wwMS.

Natalizumab, a monoclonal antibody directed against α4 integrin, is a highly efficacious treatment commonly used in relapsing remitting multiple sclerosis. Natalizumab is associated with the potentially fatal, rare, demyelinating, opportunistic brain infection, progressive multifocal leukoencephalopathy (PML). Prognosis and disability from PML are determined by early diagnosis.Written tools are mandated in Australia and other prescribing countries with the aim to help patients understand the risks associated with treatment and ensure familiarity with the early symptoms of PML. We aimed to assess if these tools achieve such an outcome.A cross-sectional survey was conducted using a convenience sample of multiple sclerosis patients prescribed natalizumab presenting to the infusion centre at a major tertiary hospital. Patients were offered a multi-choice questionnaire to assess their knowledge on the treatment risks and surveillance requirements of their therapy. Three specific questions were highlighted by the researchers as crucial to patient understanding of PML and defined as basic knowledge.A total of 48 patients in our hospital was prescribed natalizumab; 37 responded. A total of 16 (43.2%) patients answered all three basic knowledge questions correctly. There was no difference in the ability to answer these questions based on length of treatment or co-ownership knowledge between patients with base knowledge and without.Natalizumab is associated with an increased risk of PML. Early detection and treatment of PML results in improved patient outcomes. Patient knowledge and co-partnership in the utilisation of PML risk tools is relevant in ensuring early detection. Our findings question the ability of currently sanctioned tools to inform patients of basic knowledge of PML and their risk of developing PML. A future study with a repetitive education approach and repeating the questionnaire at multiple time points would be of interest.

The growing range of effective therapies for relapsing remitting multiple sclerosis (RRMS) brings with it a wider range of possible complications requiring broader considerations and greater vigilance. Alemtuzumab is a humanized monoclonal antibody against CD52 that is highly effective in the treatment of RRMS and approved in many countries around the world. We describe a case presenting with a complication not previously seen.

Objectives To analyse John Cunningham virus (JCV) serology in natalizumab treated patients over time and assess whether seroconversion was influenced by natalizumab treatment and prior immunosuppressive therapy. Methods Patients treated with natalizumab for relapsing-remitting multiple sclerosis at six tertiary hospitals in Melbourne, Australia (n=960) were longitudinally assessed for change in JCV serostatus. Duration of exposure to natalizumab and exposure to prior immunosuppressive therapy was documented. Results Two hundred and ninety-four patients (30.6%) had positive JCV serostatus when commencing natalizumab while 666 patients (69.4%) were JCV negative. JCV serostatus changed in 148 of 960 longitudinally followed patients (15.4%) over a mean observation period of 2.7 years. Durable positive seroconversion was seen in 81 of 666 initially JCV negative patients (12.2% over 2.7 years, 4.4% per year). Conversely, durable negative seroconversion was seen in 17 of 294 initially JCV positive patients (5.8% in 2.7 years, 2.1% per year). Fluctuating JCV serostatus was seen in 50 of 960 patients (5.2%). Durable positive seroconversion was more common early in therapy with natalizumab, with 31.9% occurring in the first year of exposure. Positive seroconversion rates were not increased in patients who had received prior treatment with methylprednisolone. No positive seroconversion events were documented in patients exposed to mitoxantrone. Conclusions In contrast to recently published data from colleagues in France and Germany, in our longitudinal cohort study rates of durable positive JCV seroconversion correlate closely with expected background rates of JCV seroconversion in the general population. In addition, JCV seroconversion and positive serostatus is not increased in patients with prior exposure to immunosuppressive agents. The low seroconversion rates seen after the first year of exposure suggests that less frequent JCV testing of natalizumab treated patients may be safe.