Efficacy and safety of autologous haematopoietic stem cell transplantation versus alemtuzumab, ocrelizumab, ofatumumab or cladribine in relapsing remitting multiple sclerosis (StarMS): protocol for a randomised controlled trial.

INTRODUCTION: Autologous haematopoietic stem cell transplantation (aHSCT) is increasingly used as treatment for patients with active multiple sclerosis (MS), typically after failure of disease-modifying therapies (DMTs). A recent phase III trial, 'Multiple Sclerosis International Stem Cell Transplant, MIST', showed that aHSCT resulted in prolonged time to disability progression compared with DMTs in patients with relapsing remitting MS (RRMS). However, the MIST trial did not include many of the current high-efficacy DMTs (alemtuzumab, ocrelizumab, ofatumumab or cladribine) in use in the UK within the control arm, which are now offered to patients with rapidly evolving severe MS (RES-MS) who are treatment naïve. There remain, therefore, unanswered questions about the relative efficacy and safety of aHSCT over these high-efficacy DMTs in these patient groups. The StarMS trial (Autologous Stem Cell Transplantation versus Alemtuzumab, Ocrelizumab, Ofatumumab or Cladribine in Relapsing Remitting Multiple Sclerosis) will assess the efficacy, safety and long-term impact of aHSCT compared with high-efficacy DMTs in patients with highly active RRMS despite the use of standard DMTs or in patients with treatment naïve RES-MS. METHODS AND ANALYSIS: StarMS is a multicentre parallel-group rater-blinded randomised controlled trial with two arms. A total of 198 participants will be recruited from 19 regional neurology secondary care centres in the UK. Participants will be randomly allocated to the aHSCT arm or DMT arm in a 1:1 ratio. Participants will remain in the study for 2 years with follow-up visits at 3, 6, 9, 12, 18 and 24 months postrandomisation. The primary outcome is the proportion of patients who achieve 'no evidence of disease activity' during the 2-year postrandomisation follow-up period in an intention to treat analysis. Secondary outcomes include efficacy, safety, cost-effectiveness and immune reconstitution of aHSCT and the four high-efficacy DMTs. ETHICS AND DISSEMINATION: The study was approved by the Yorkshire and Humber-Leeds West Research Ethics Committee (20/YH/0061). Participants will provide written informed consent prior to any study specific procedures. The study results will be submitted to a peer-reviewed journal and abstracts will be submitted to relevant national and international conferences. TRIAL REGISTRATION NUMBER: ISRCTN88667898.

A Novel approach using O-CVP to treat paraneoplastic NMO spectrum disorder associated with follicular lymphoma.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune neuroinflammatory disorder of the central nervous system that very rarely may be a paraneoplastic phenomenon. We describe the case of a woman with a longitudinally extensive transverse myelitis (LETM). We identified a previously undiagnosed, follicular lymphoma and she was treated with the immunochemotherapy regime (obinutuzumab, cyclophosphamide, vincristine and prednisolone; O-CVP) for paraneoplastic NMOSD. Following two cycles, there was almost complete radiological remission of the myelitis and the patient showed some improvement in her neurological function. This case illustrates the heterogeneous aetiology that LETM may have and that O-CVP may be used as therapeutic option in patients with NMOSD driven by follicular lymphoma.

Key demographics and psychological skills associated with adjustment to progressive Multiple Sclerosis early in the diagnosis.

Background/purpose: Being diagnosed with a progressive type of multiple sclerosis (MS) has been associated with worse psychological outcomes compared to relapsing-remitting type. Previous studies of adjustment to MS have primarily focused on relapsing-remitting type MS. The present study aims to examine psychological adjustment for people newly diagnosed with progressive multiple sclerosis. Methods: This was a multicenter cross-sectional survey of 189 people newly diagnosed with progressive MS. A composite measure of psychological adjustment was created from questionnaires measuring psychological distress, positive affect, perceived-stress, life satisfaction and self-concept. Predictor variables included coping strategies, social support, relationship with partner, psychological vulnerability, MS-related beliefs, and responses to symptoms. Data were analysed using a regularised regression model to indicate which group of all variables are associated with adjustment. Results: People who were older (b = 0.17(0.07), p = 0.02), in employment (b = 0.40 (0.17), p = 0.01), and with lower illness severity (b = -0.24 (0.08), p = 0.001) showed better adjustment. Based on a Lasso regression, the most important psychological and demographic variables associated with lower adjustment (out-of-sample cross-validation R 2 = 62.6%) were lower MS self-efficacy and higher avoidance, cognitive vulnerability, embarrassment avoidance, conflict, helplessness, and secondary progressive MS type. Conclusions and implications: Helping newly diagnosed people to find ways to tolerate anxiety-causing situations by encouraging acceptance may help people adjust to progressive MS by lowering their avoidance. Further, building confidence in managing the illness and addressing relationship issues are key focus areas in psychological interventions for people with progressive multiple sclerosis.

"I wanna live and not think about the future" what place for advance care planning for people living with severe multiple sclerosis and their families? A qualitative study.

BACKGROUND: Little is known about how people with multiple sclerosis (MS) and their families comprehend advance care planning (ACP) and its relevance in their lives. AIM: To explore under what situations, with whom, how, and why do people with MS and their families engage in ACP. METHODS: We conducted a qualitative study comprising interviews with people living with MS and their families followed by an ethical discussion group with five health professionals representing specialties working with people affected by MS and their families. Twenty-seven people with MS and 17 family members were interviewed between June 2019 and March 2020. Interviews and the ethical discussion group were audio-recorded and transcribed verbatim. Data were analysed using the framework approach. RESULTS: Participants' narratives focused on three major themes: (i) planning for an uncertain future; (ii) perceived obstacles to engaging in ACP that included uncertainty concerning MS disease progression, negative previous experiences of ACP discussions and prioritising symptom management over future planning; (iii) Preferences for engagement in ACP included a trusting relationship with a health professional and that information then be shared across services. Health professionals' accounts from the ethical discussion group departed from viewing ACP as a formal document to that of an ongoing process of seeking preferences and values. They voiced similar concerns to people with MS about uncertainty and when to initiate ACP-related discussions. Some shared concerns of their lack of confidence when having these discussions. CONCLUSION: These findings support the need for a whole system strategic approach where information about the potential benefits of ACP in all its forms can be shared with people with MS. Moreover, they highlight the need for health professionals to be skilled and trained in engaging in ACP discussions and where information is contemporaneously and seamlessly shared across services.

Autologous Hematopoietic Stem Cell Transplantation in Active Multiple Sclerosis: A Real-world Case Series.

OBJECTIVE: To examine outcomes in people with multiple sclerosis (PwMS) treated with autologous hematopoietic stem cell transplantation (AHSCT) in a real-world setting. METHODS: This was a retrospective cohort study of PwMS treated with AHSCT at 2 centers in London, UK, consecutively between 2012 and 2019 who had ≥6 months of follow-up or died at any time. Primary outcomes were survival free of multiple sclerosis (MS) relapses, MRI new lesions, and worsening of Expanded Disability Status Scale (EDSS) score. Adverse events rates were also examined. RESULTS: The cohort includes 120 PwMS; 52% had progressive MS (primary or secondary) and 48% had relapsing-remitting MS. At baseline, the median EDSS score was 6.0; 90% of the evaluable cases showed MRI activity in the 12 months preceding AHSCT. Median follow-up after AHSCT was 21 months (range 6-85 months). MS relapse-free survival was 93% at 2 years and 87% at 4 years after AHSCT. No new MRI lesions were detected in 90% of participants at 2 years and in 85% at 4 years. EDSS score progression-free survival (PFS) was 75% at 2 years and 65% at 4 years. Epstein-Barr virus reactivation and monoclonal paraproteinemia were associated with worse PFS. There were 3 transplantation-related deaths within 100 days (2.5%), all after fluid overload and cardiac or respiratory failure. CONCLUSIONS: Efficacy outcomes of AHSCT in this real-world cohort are similar to those reported in more stringently selected clinical trial populations, although the risks may be higher. CLASSIFICATION OF EVIDENCE: This study is rated Class IV because of the uncontrolled, open-label design.

COVID-19 leukoencephalopathy with subacute magnetic resonance imaging findings of vasculitis and demyelination.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) commonly results in a respiratory illness in symptomatic patients; however, those critically ill can develop a leukoencephalopathy. We describe two patients who had novel subacute MRI findings in the context of coronavirus disease 2019 (COVID-19) leukoencephalopathy, which we hypothesize could implicate a potent small-vessel vasculitis, ischemic demyelination and the presence of prolonged ischemia. Recent evidence of the direct neuroinvasiness of SARS-CoV-2 leading to ischemia and vascular damage supports this hypothesis.

Atypical inflammatory demyelinating syndrome with central and peripheral nerve involvement.

We report a patient who has peripheral demyelination in the form of chronic inflammatory demyelinating polyneuropathy (CIDP) with central demyelination following a relapsing-remitting disease course. The patient developed bilateral sequential optic neuritis predating the diagnosis of CIPD, then developed a profound brainstem syndrome with ataxia, dysarthria, a complex eye movement disorder, visual disturbance and urinary incontinence. Interval imaging fulfilled McDonald criteria for multiple sclerosis (MS) with a right parieto-occipital tumefactive lesion showing contrast enhancement and new lesions in the right temporal white matter and midbrain tegmentum. Oligoclonal bands (OCBs) were matched and serum antibodies against aquaporin-4 (AQP-4) and myelin oligodendrocyte glycoprotein (MOG) were negative. Genetic sequence analysis and deletion/duplication testing revealed variants of uncertain significance with compound heterozygosity for point mutations in two genes, DYNC1H1 and SH3TC2, which are associated with Charcot-Marie-Tooth (CMT) disease though the patient was negative for known CMT mutations. The patient responded poorly to steroids and regular intravenous immunoglobulin (IVIg) but clinically improved following aggressive immunomodulatory therapy with pulsed steroids and plasmapheresis, followed by Rituximab. Combined central and peripheral demyelination (CCPD) is rare. Autoimmune mechanisms are postulated in the pathogenesis. Whether overlap of central and pe- ripheral demyelination is coincidental or caused by a shared epitope in both the peripheral and central nervous systems still remains to be elucidated. There is no clear therapeutic consensus in the treatment of both central and peripheral demyelination, though immunomodulating treatment strategies may minimise disability and improve prognosis.

Progressive bulbar symptomatology due to vascular brainstem compression.

Symptomatic brainstem compression from vertebral artery dolichoectasia is rare. There are no recognised diagnostic or treatment criteria to guide management of this disease. We report a case of medullary compression and cerebral ischaemia from an enlarged and tortuous vertebral artery. Our patient developed progressive dysphonia and dysphagia. Cerebral MRI revealed compression of the medulla oblongata by a right ectatic vertebral artery and a right occipital lobe infarct. Other causes of bulbar dysfunction were ruled out. He was treated with anticoagulation and underwent percutaneous endoscopic gastrostomy. We review selected literature on the presentation, diagnosis and management of this rare neurologic condition.

Improving MS patients' understanding of treatment risks and benefits in clinical consultations: A randomised crossover trial.

BACKGROUND: Multiple Sclerosis (MS) patients find it difficult to understand the complex risk-benefit profiles of disease-modifying drugs. An evidence-based protocol was designed to improve patient's understanding of treatment information: Benefit and Risk Information for Medication in Multiple Sclerosis (BRIMMS). OBJECTIVE: A feasibility study to evaluate whether the BRIMMS protocol can improve MS patients' treatment understanding and reduce conflict in treatment decisions compared to consultation as usual. DESIGN: Single-blind 4-condition 4-period randomised crossover trial. Hypothetical treatment information was presented to MS patients in a faux 20 minute consultation session using the BRIMMS protocol (aural and visual) or as a usual consultation (aural and visual). Patients were randomised to the order in which they received the four consultation styles. PARTICIPANTS: 24 patients diagnosed with relapsing-remitting MS. MEASURES: Patients were assessed on their comprehension of treatment information, decisional conflict and feedback on consultation styles. Disease and demographic information was also collected. RESULTS: Treatment understanding was greater for both BRIMMS visual and BRIMMS aural, compared to usual consultations in visual or aural format. Similarly, BRIMMS visual and BRIMMS aural reduced decisional conflict compared to usual consultations in visual or aural formats. All comparisons were p<0.001. Cognitive status was not related to understanding in the BRIMMS protocol, but was negatively related with usual consultation. Conversely, mood influenced understanding on the BRIMMS protocol but not for usual consultation. CONCLUSIONS: BRIMMS protocol offers an effective, evidence-based tool for presenting treatment information in consultations with MS patients and is not influenced by cognition. TRIAL REGISTRATION: ISRCTN17318966.

Subcutaneous cladribine to treat multiple sclerosis: experience in 208 patients.

OBJECTIVE: To report on safety and effectiveness of subcutaneous cladribine (Litak®) in multiple sclerosis (MS) patients. METHODS: Litak® was offered to MS-patients irrespective of disease course. Litak® 10 mg was administered for 3-4 days during week 1. Based on lymphocyte count at week 4, patients received another 0-3 doses at week 5. A second course was administered 11 months later. Follow-up included adverse events, relapses, expanded disability status scale (EDSS), 9-hole-peg and Timed-25-foot-walking tests, no-evidence-of-disease-activity (NEDA), no-evidence-of-progression-or-active-disease (NEPAD), MRI, cerebrospinal fluid (CSF) neurofilament light chain (NfL), and lymphocyte counts. RESULTS: In all, 208 patients received at least one course of treatment. Age at baseline was 44 (17-72) years and EDSS 0-8.5. Cladribine was generally well tolerated. One myocardial infarction, one breast cancer, and three severe skin reactions occurred without long-term sequelae. Two patients died (one pneumonia, one encephalitis). Lymphopenia grade 3 occurred in 5% and grade 4 in 0.5%. In 94 out of 116 pwMS with baseline and follow-up (BaFU) data after two treatment courses, EDSS remained stable or improved. At 18 months, 64% of patients with relapsing MS and BaFU data (n = 39) had NEDA. At 19 months, 62% of patients with progressive MS and BaFU data (n = 13) had NEPAD. Of n = 13 patients whose CSF-NfL at baseline was elevated, 77% were normalised within 12 months. CONCLUSIONS: Litak® was well tolerated. Effectiveness in relapsing MS appeared similar to cladribine tablets and was encouraging in progressive MS. Our data suggest cladribine may be safe and effective in MS-patients irrespective of their disease stage.

A realist review of advance care planning for people with multiple sclerosis and their families.

BACKGROUND: Advance care planning (ACP) is reported to improve the quality of outcomes of care among those with life-limiting conditions. However, uptake is low among people living with multiple sclerosis (MS) and little is known about why or how people with MS engage in this process of decision-making. AIMS: To develop and refine an initial theory on engagement in ACP for people with MS and to identify ways to improve its uptake for those who desire it. METHODS: Realist review following published protocol and reporting following Realist and Meta-narrative Evidence Synthesis: Evolving Standards (RAMESES) guidelines. A multi-disciplinary team searched MEDLINE, PsychInfo, CINAHL, Scopus, Web of Science, Embase, Google Scholar in addition to other sources from inception to August 2019. Quantitative or qualitative studies, case reports, and opinion or discussion articles related to ACP and/or end of life discussions in the context of MS were included, as well as one article on physical disability and one on motor neuron disease, that contributed important contextual information. Researchers independently screened abstracts and extracted data from full-text articles. Using abductive and retroductive analysis, each article was examined for evidence to support or refute 'context, mechanism, and outcome' (CMO) hypotheses, using the Integrated Behaviour Model to guide theory development. Quality was assessed according to methodological rigour and relevance of evidence. Those studies providing rich descriptions were synthesised using a realist matrix to identify commonalities across CMO configurations. RESULTS: Of the 4,034 articles identified, 33 articles were included in the synthesis that supported six CMO hypotheses that identified contexts and mechanisms underpinning engagement in ACP for people with MS and included: acceptance of their situation, prior experiences, confidence, empowerment, fear (of being a burden, of death and of dying) and the desire for autonomy. Acceptance of self as a person with a life-limiting illness was imperative as it enabled people with MS to see ACP as pertinent to them. We identified the context of MS-its long, uncertain disease trajectory with periods of stability punctuated by crisis-inhibited triggering of mechanisms. Similarly, the absence of skills and confidence in advanced communication skills among health professionals prevented possibilities for ACP discussions taking place. CONCLUSION: Although mechanisms are inhibited by the context of MS, health professionals can facilitate greater uptake of ACP among those people with MS who want it by developing their skills in communication, building trusting relationships, sharing accurate prognostic information and sensitively discussing death and dying.

Effect of Short-term Integrated Palliative Care on Patient-Reported Outcomes Among Patients Severely Affected With Long-term Neurological Conditions: A Randomized Clinical Trial.

Importance: Palliative care has shown benefits in reducing symptom intensity and quality of life in patients with advanced cancer. However, high-quality evidence to support palliative care policy and service developments for patients with long-term neurological conditions (LTNCs) is lacking. Objective: To determine the effectiveness of a short-term integrated palliative care (SIPC) intervention for people with LTNCs. Design, Setting, and Participants: Multicenter, phase 3, randomized clinical trial conducted from April 1, 2015, to November 30, 2017, with a last follow-up date of May 31, 2018, in 7 UK hospitals with both neurology and palliative care services. A total of 535 patients with LTNC were assessed for eligibility and 350 were randomized. Inclusion criteria were patients 18 years or older with any advanced stage of multiple sclerosis, motor neuron disease, idiopathic Parkinson disease multiple system atrophy, or progressive supranuclear palsy. Data were analyzed from November 2018 to March 2019. Interventions: Patients were randomized 1:1 using minimization method to receive SIPC (intervention, n = 176) or standard care (control, n = 174). Main Outcomes and Measures: Primary outcome was change in 8 key palliative care symptoms from baseline to 12-weeks, measured by the Integrated Palliative care Outcome Scale for neurological conditions. Secondary outcomes included change in the burden of other symptoms, health-related quality of life, caregiver burden, and costs. Data were collected and analyzed blindly by intention to treat. Results: A total of 350 patients (mean [SD] age 67 [12] years; years since diagnosis, 12 [range, 0-56]; 51% men; 49% requiring considerable assistance) with an advanced stage of LTNC were recruited, along with informal caregivers (n = 229). There were no between-group differences in primary outcome (effect size, -0.16; 95% CI, -0.37 to 0.05), any other patient-reported outcomes, adverse events, or survival. Although there was more symptom reduction in the SIPC group in relation to mean change in primary outcome, the difference between the groups was not statistically significant (-0.78; 95% CI, -1.29 to -0.26 vs -0.28; 95% CI, -0.82 to 0.26; P = .14). There was a decrease in mean health and social care costs from baseline to 12 weeks -$1367 (95% CI, -$2450 to -$282) in the SIPC group and -653 (95% CI, -$1839 to -$532) in the control group, but this difference was not statistically significant (P = .12). SIPC was perceived by patients and caregivers as building resilience, attending to function and deficits, and enabling caregivers. Conclusions and Relevance: In this study, SIPC was not statistically significantly different from standard care for the patient-reported outcomes. However, SIPC was associated with lower cost, and in qualitative analysis was well-received by patients and caregivers, and there were no safety concerns. Further research is warranted. Trial Registration: isrctn.org Identifier: ISRCTN18337380.

The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings.

Preliminary clinical data indicate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with neurological and neuropsychiatric illness. Responding to this, a weekly virtual coronavirus disease 19 (COVID-19) neurology multi-disciplinary meeting was established at the National Hospital, Queen Square, in early March 2020 in order to discuss and begin to understand neurological presentations in patients with suspected COVID-19-related neurological disorders. Detailed clinical and paraclinical data were collected from cases where the diagnosis of COVID-19 was confirmed through RNA PCR, or where the diagnosis was probable/possible according to World Health Organization criteria. Of 43 patients, 29 were SARS-CoV-2 PCR positive and definite, eight probable and six possible. Five major categories emerged: (i) encephalopathies (n = 10) with delirium/psychosis and no distinct MRI or CSF abnormalities, and with 9/10 making a full or partial recovery with supportive care only; (ii) inflammatory CNS syndromes (n = 12) including encephalitis (n = 2, para- or post-infectious), acute disseminated encephalomyelitis (n = 9), with haemorrhage in five, necrosis in one, and myelitis in two, and isolated myelitis (n = 1). Of these, 10 were treated with corticosteroids, and three of these patients also received intravenous immunoglobulin; one made a full recovery, 10 of 12 made a partial recovery, and one patient died; (iii) ischaemic strokes (n = 8) associated with a pro-thrombotic state (four with pulmonary thromboembolism), one of whom died; (iv) peripheral neurological disorders (n = 8), seven with Guillain-Barré syndrome, one with brachial plexopathy, six of eight making a partial and ongoing recovery; and (v) five patients with miscellaneous central disorders who did not fit these categories. SARS-CoV-2 infection is associated with a wide spectrum of neurological syndromes affecting the whole neuraxis, including the cerebral vasculature and, in some cases, responding to immunotherapies. The high incidence of acute disseminated encephalomyelitis, particularly with haemorrhagic change, is striking. This complication was not related to the severity of the respiratory COVID-19 disease. Early recognition, investigation and management of COVID-19-related neurological disease is challenging. Further clinical, neuroradiological, biomarker and neuropathological studies are essential to determine the underlying pathobiological mechanisms that will guide treatment. Longitudinal follow-up studies will be necessary to ascertain the long-term neurological and neuropsychological consequences of this pandemic.

Clinical Features and Genetic Risk of Demyelination Following Anti-TNF Treatment.

BACKGROUND: Anti-TNF exposure has been linked to demyelination events. We sought to describe the clinical features of demyelination events following anti-TNF treatment and to test whether affected patients were genetically predisposed to multiple sclerosis [MS]. METHODS: We conducted a case-control study to describe the clinical features of demyelination events following anti-TNF exposure. We compared genetic risk scores [GRS], calculated using carriage of 43 susceptibility loci for MS, in 48 cases with 1219 patients exposed to anti-TNF who did not develop demyelination. RESULTS: Overall, 39 [74%] cases were female. The median age [range] of patients at time of demyelination was 41.5 years [20.7-63.2]. The median duration of anti-TNF treatment was 21.3 months [0.5-99.4] and 19 [36%] patients were receiving concomitant immunomodulators. Most patients had central demyelination affecting the brain, spinal cord, or both. Complete recovery was reported in 12 [23%] patients after a median time of 6.8 months [0.1-28.7]. After 33.0 months of follow-up, partial recovery was observed in 29 [55%] patients, relapsing and remitting episodes in nine [17%], progressive symptoms in three [6%]: two [4%] patients were diagnosed with MS. There was no significant difference between MS GRS scores in cases (mean -3.5 × 10-4, standard deviation [SD] 0.0039) and controls [mean -1.1 × 10-3, SD 0.0042] [p = 0.23]. CONCLUSIONS: Patients who experienced demyelination events following anti-TNF exposure were more likely female, less frequently treated with an immunomodulator, and had a similar genetic risk to anti-TNF exposed controls who did not experience demyelination events. Large prospective studies with pre-treatment neuroimaging are required to identify genetic susceptibility loci.

EAN Guideline on Palliative Care of People with Severe, Progressive Multiple Sclerosis.

Background and Purpose: Patients with severe, progressive multiple sclerosis (MS) have complex physical and psychosocial needs, typically over several years. Few treatment options are available to prevent or delay further clinical worsening in this population. The objective was to develop an evidence-based clinical practice guideline for the palliative care of patients with severe, progressive MS. Methods: This guideline was developed using the Grading of Recommendations Assessment, Development and Evaluation methodology. Formulation of the clinical questions was performed in the Patients-Intervention-Comparator-Outcome format, involving patients, carers and healthcare professionals (HPs). No uniform definition of severe MS exists: in this guideline, constant bilateral support required to walk 20 m without resting (Expanded Disability Status Scale score >6.0) or higher disability is referred to. When evidence was lacking for this population, recommendations were formulated using indirect evidence or good practice statements were devised. Results: Ten clinical questions were formulated. They encompassed general and specialist palliative care, advance care planning, discussing with HPs the patient's wish to hasten death, symptom management, multidisciplinary rehabilitation, interventions for caregivers and interventions for HPs. A total of 34 recommendations (33 weak, 1 strong) and seven good practice statements were devised. Conclusions: The provision of home-based palliative care (either general or specialist) is recommended with weak strength for patients with severe, progressive MS. Further research on the integration of palliative care and MS care is needed. Areas that currently lack evidence of efficacy in this population include advance care planning, the management of symptoms such as fatigue and mood problems, and interventions for caregivers and HPs.

Real-world incidence of fingolimod-associated macular oedema.

BACKGROUND: Fingolimod (Gilenya, Novartis, Basel Switzerland) 0.5 mg orally once-daily is widely used for relapsing-remitting multiple sclerosis. Patients are usually screened four months after starting fingolimod for fingolimod-associated macular oedema (FAME). Large registration trials with stringent eligibility criteria have reported a FAME incidence of 0 - 2.08%. OBJECTIVES: To determine the real-world incidence of FAME in a London population, and to describe the clinical characteristics and management of confirmed cases. METHODS: All patients started on fingolimod from September 2012 to September 2018 were referred for ophthalmology clinical examination and macular spectral-domain optical coherence tomography (SD-OCT) at four months after starting treatment. Exclusion criteria were failure to attend or non-gradable OCT images. RESULTS: Of 228 patients, two had FAME at initial screening, giving an incidence of 0.88% (95% confidence interval 0.10-3.10). Another case emerged subsequently, at 637 days, resulting in a final incidence of 1.32% (95% confidence interval 0.30-3.80). Fingolimod was discontinued in two cases. FAME resolved in all cases within two to 10 months, with no persistent visual loss or symptoms. CONCLUSIONS: The real-world FAME incidence is consistent with fingolimod registration studies. FAME may have a delayed onset and may be better detected with newer OCT devices.