| 1. |
- Allen-Philbey, Kimberley, et al.
(author)
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Subcutaneous cladribine to treat multiple sclerosis : experience in 208 patients
- 2021
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In: Therapeutic Advances in Neurological Disorders. - : SAGE Publications. - 1756-2856 .- 1756-2864. ; 14
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Journal article (peer-reviewed)abstract
- 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.
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| 2. |
- Giovannoni, G., et al.
(author)
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Smouldering multiple sclerosis: the ‘real MS’
- 2022
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In: Therapeutic Advances in Neurological Disorders. - : SAGE Publications. - 1756-2856 .- 1756-2864. ; 15
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Journal article (peer-reviewed)abstract
- Using a philosophical approach or deductive reasoning, we challenge the dominant clinico-radiological worldview that defines multiple sclerosis (MS) as a focal inflammatory disease of the central nervous system (CNS). We provide a range of evidence to argue that the ‘real MS’ is in fact driven primarily by a smouldering pathological disease process. In natural history studies and clinical trials, relapses and focal activity revealed by magnetic resonance imaging (MRI) in MS patients on placebo or on disease-modifying therapies (DMTs) were found to be poor predictors of long-term disease evolution and were dissociated from disability outcomes. In addition, the progressive accumulation of disability in MS can occur independently of relapse activity from early in the disease course. This scenario is underpinned by a more diffuse smouldering pathological process that may affect the entire CNS. Many putative pathological drivers of smouldering MS can be potentially modified by specific therapeutic strategies, an approach that may have major implications for the management of MS patients. We hypothesise that therapeutically targeting a state of ‘no evident inflammatory disease activity’ (NEIDA) cannot sufficiently prevent disability accumulation in MS, meaning that treatment should also focus on other brain and spinal cord pathological processes contributing to the slow loss of neurological function. This should also be complemented with a holistic approach to the management of other systemic disease processes that have been shown to worsen MS outcomes. © The Author(s), 2022.
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| 3. |
- Hakkarainen, Katja Marja, et al.
(author)
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Pregnancy outcomes after exposure to interferon beta : a register-based cohort study among women with MS in Finland and Sweden
- 2020
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In: Therapeutic advances in neurological disorders. - : Sage Publications. - 1756-2856 .- 1756-2864. ; 13
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Journal article (peer-reviewed)abstract
- Background: Our aim was to estimate and compare the prevalence of adverse pregnancy outcomes among pregnant women with multiple sclerosis (MS) exposed to interferon beta (IFNB) and among women with MS unexposed to any MS disease-modifying drug (MSDMD).Methods: This cohort study used Finnish (1996-2014) and Swedish (2005-2014) national register data. Women with MS having IFNB dispensed 6 months before or during pregnancy as the only medication were considered as IFNB exposed (only IFNB-exposed), whereas women with MS unexposed to any MSDMD were considered unexposed (MSDMD-unexposed). Prevalence was described and compared using log-binomial or logistic regression and adjusted for potential confounders including maternal age and comorbidity.Results: Among 2831 pregnancies, 2.2% of the only IFNB-exposed and 4.0% of the MSDMD-unexposed women had serious adverse pregnancy outcomes [elective termination of pregnancy due to foetal anomaly (TOPFA), major congenital anomaly (MCA) in live, or stillbirth]. After adjustments, the prevalence of serious adverse pregnancy outcomes was lower among the only IFNB-exposed compared with the MSDMD-unexposed [relative risk 0.55, 95% confidence interval (CI) 0.31-0.96]. The prevalence of individual outcomes, including MCA, spontaneous abortions, and stillbirths was not increased with IFNB exposure. Women with MS exposed to IFNB appeared more likely to terminate their pregnancy for reasons other than foetal anomaly, compared with MSDMD-unexposed pregnant MS patients (odds ratio 1.71, 95% CI 1.06-2.78).Conclusion: In this large cohort study, no increase in the prevalence of adverse pregnancy outcomes was observed in women with MS exposed to IFNB compared with MS patients unexposed to any MSDMDs. This study together with other evidence led to a change in the labels of the IFNB products in September 2019 in the European Union, and IFNB use today may be considered during pregnancy, if clinically needed.
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| 4. |
- Hupperts, R., et al.
(author)
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Efficacy of prolonged-release fampridine versus placebo on walking ability, dynamic and static balance, physical impact of multiple sclerosis, and quality of life: an integrated analysis of MOBILE and ENHANCE
- 2022
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In: Therapeutic Advances in Neurological Disorders. - : SAGE Publications. - 1756-2856 .- 1756-2864. ; 15
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Journal article (peer-reviewed)abstract
- Background: MOBILE and ENHANCE were similarly designed randomized trials of walking-impaired adults with relapsing-remitting or progressive multiple sclerosis (MS) who received placebo or 10 mg prolonged-release (PR)-fampridine twice daily for 24 weeks. Both studies showed sustained and clinically meaningful improvement in broad measures of walking and balance over 24 weeks of PR-fampridine treatment. Objective: To evaluate the functional benefits and safety of PR-fampridine versus placebo using a post hoc integrated efficacy analysis of MOBILE and ENHANCE data. Methods: Data from the intention-to-treat (ITT) populations of MOBILE and ENHANCE studies were pooled in a post hoc analysis based on the following outcome measures: 12-item MS Walking Scale (MSWS-12), Timed Up and Go (TUG) speed, Berg Balance Scale (BBS), MS Impact Scale physical impact subscale (MSIS-29 PHYS), EQ-5D utility index score, visual analogue scale (VAS), and adverse events. The primary analysis was the proportion of people with MS (PwMS) with a mean improvement in MSWS-12 score (⩾8 points) from baseline over 24 weeks. A subgroup analysis based on baseline characteristics was performed. Findings: In the ITT population (N = 765; PR-fampridine, n = 383; placebo, n = 382), a greater proportion of PR-fampridine–treated PwMS than placebo-treated PwMS achieved a clinically meaningful improvement in the MSWS-12 scale over 24 weeks (44.3% versus 33.0%; p < 0.001). PR-fampridine MSWS-12 responders demonstrated greater improvements from baseline in TUG speed, BBS score, MSIS-29 PHYS score, and EQ-5D utility index and VAS scores versus PR-fampridine MSWS-12 nonresponders and placebo. Subgroup analyses based on baseline characteristics showed consistency in the effects of PR-fampridine. Conclusion: The pooled analysis of MOBILE and ENHANCE confirms previous evidence that treatment with PR-fampridine results in clinically meaningful improvements in walking, mobility and balance, self-reported physical impact of MS, and quality of life and is effective across a broad range of PwMS.
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| 5. |
- Li, XL, et al.
(author)
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Autoimmune glial fibrillary acidic protein astrocytopathy with lesions distributed predominantly in the entire spinal cord
- 2020
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In: Therapeutic advances in neurological disorders. - : SAGE Publications. - 1756-2856 .- 1756-2864. ; 13, s. 1756286420909973-
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Journal article (other academic/artistic)abstract
- Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy has been considered a novel central nervous system autoimmune disease characterized by relapse and responsiveness to corticosteroid with a specific GFAP-Immunoglobulin G (IgG) being noted in cerebrospinal fluid. We report the case of a 21-year-old girl presenting with dysuria and weariness, who subsequently developed blurry vision, slight dysphagia, slurred speech, and sensory abnormality. GFAP-IgG was detected in her cerebrospinal fluid. Magnetic resonance imaging using both T2-weighted and contrast-enhanced T1-weighted images revealed a rare finding of lesions distributed mainly in the entire spinal cord rather than typical brain lesions. After treating with corticosteroids, her clinical symptoms were alleviated, and the spinal cord lesion enhancement was reduced. Our observations extend the clinical spectrum of autoimmune GFAP astrocytopathy. We suggest that rare distributed lesions in the entire spinal cord in patients with autoimmune GFAP astrocytopathy cannot be ignored by neurologists. The identification of potential atypical lesions broadens the understanding of autoimmune GFAP astrocytopathy.
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| 6. |
- Lycke, Jan, 1956, et al.
(author)
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Intensive immunosuppression followed by autologous hematopoietic stem cell transplantation for the treatment of multiple sclerosis
- 2020
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In: Therapeutic Advances in Neurological Disorders. - : SAGE Publications. - 1756-2856 .- 1756-2864. ; 13
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Journal article (peer-reviewed)abstract
- Autologous hematopoietic stem cell transplantation (AHSCT) to treat multiple sclerosis (MS) has mostly been used in devastating cases as the last option to stop further neurological deterioration. However, evidence from several retrospective clinical trials indicates that young, less disabled patients with highly inflammatory active MS are the most likely to benefit from AHSCT, and after moving from high-intensity to nonmyeloablative procedures the tolerability of AHSCT has increased and its associated risk and mortality have declined considerably. Recent meta-analyses and randomized clinical trials show that AHSCT is more effective than currently approved disease-modifying therapies (DMTs), with suppression of disease activity in 70-90% of patients and long-term cessation of disease activity in two-thirds of treated patients. The rationale for AHSCT is to eliminate autoimmunity and achieve immune resetting by intense immunosuppression followed by infusion of autologous hematopoietic stem cells. Similar effects on the immune system have been suggested for cladribine and alemtuzumab treatment and, together with AHSCT, they constitute the induction or immune-reconstitution therapies for MS. Although, further randomized controlled trials of AHSCT for MS are needed, it has become clear that improved patient selection and lower intensity conditioning regimens have reduced AHSCT associated risks and mortality and strengthened the position of AHSCT among other DMTs. Do we have enough experience and scientific support for AHSCT in MS to move from an exclusive treatment for aggressive, treatment-resistant MS and acquire broader indications, similar to other effective DMTs?
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| 7. |
- Lycke, Jan, 1956
(author)
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Monoclonal antibody therapies for the treatment of relapsing-remitting multiple sclerosis: differentiating mechanisms and clinical outcomes
- 2015
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In: Therapeutic Advances in Neurological Disorders. - : SAGE Publications. - 1756-2856 .- 1756-2864. ; 8:6, s. 274-293
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Journal article (peer-reviewed)abstract
- Monoclonal antibody (mAb) therapies for relapsing-remitting multiple sclerosis (MS) target immune cells or other molecules involved in pathogenic pathways with extraordinary specificity. Natalizumab and alemtuzumab are the only two currently approved mAbs for the treatment of MS, having demonstrated significant reduction in clinical and magnetic resonance imaging disease activity and disability in clinical studies. Ocrelizumab and daclizumab are in the late stages of phase III trials, and several other mAbs are in the early stages of clinical evaluation. mAbs have distinct structural characteristics (e.g. chimeric, humanized, fully human) and unique targets (e.g. blocking interactions, induction of signal transduction by receptor binding, complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity) conferring different mechanisms of action in MS. Because of these differences, mAbs for MS do not constitute a single treatment class; each must be considered individually when selecting appropriate therapy. Furthermore, in reviewing the data from clinical studies of mAbs, attention should be drawn to use of different comparators (e.g. placebo or interferon -1a) and study designs. Each mAb treatment has a unique administration schedule. In the decision to select the appropriate treatment for each individual MS patient, careful review of the benefits relative to risks of mAbs is balanced against the risk of development of MS-associated disability.
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| 8. |
- Nyholm, Dag, Professor, 1974-, et al.
(author)
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Levodopa-entacapone-carbidopa intestinal gel infusion in advanced Parkinson's disease : real-world experience and practical guidance
- 2022
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In: Therapeutic advances in neurological disorders. - : Sage Publications. - 1756-2856 .- 1756-2864. ; 15
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Research review (peer-reviewed)abstract
- As Parkinson's disease (PD) progresses, treatment needs to be adapted to maintain symptom control. Once patients develop advanced PD, an optimised regimen of oral and transdermal medications may no longer provide adequate relief of OFF periods and motor complications can emerge. At this point, patients may wish to consider a device-aided therapy (DAT) that provides continuous dopaminergic stimulation to help overcome these issues. Levodopa-entacapone-carbidopa intestinal gel (LECIG) infusion is a recently developed DAT option. The aim of this article is twofold: (1) to give an overview of the pharmacokinetics of LECIG infusion and clinical experience to date of its use in patients with advanced PD, including real-world data and patient-reported outcomes from a cohort of patients treated in Sweden, the first country where it was introduced, and (2) based on that information to provide practical guidance for healthcare teams starting patients on LECIG infusion, whether they are transitioning from oral medications or from other DATs, including recommendations for stepwise dosing calculation and titration. In terms of clinical efficacy, LECIG infusion has been shown to have a similar effect on motor function to standard levodopa-carbidopa intestinal gel (LCIG) infusion but, due to the presence of entacapone in LECIG, the bioavailability of levodopa is increased such that lower overall levodopa doses can be given to achieve therapeutically effective plasma concentrations. From a practical standpoint, LECIG infusion is delivered using a smaller cartridge and pump system than LCIG infusion. In addition, for patients previously treated with LCIG infusion who have an existing percutaneous endoscopic transgastric jejunostomy (PEG-J) system, this is compatible with the LECIG infusion system. As it is a relatively new product, the long-term efficacy and safety of LECIG infusion remain to be established; however, real-world data will continue to be collected and analysed to provide this information and help inform future clinical decisions.
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| 9. |
- Reale, G, et al.
(author)
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Dual anti-platelet therapy for secondary prevention in intracranial atherosclerotic disease: a network meta-analysis
- 2022
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In: Therapeutic advances in neurological disorders. - : SAGE Publications. - 1756-2856 .- 1756-2864. ; 15, s. 17562864221114716-
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Journal article (peer-reviewed)abstract
- Intracranial arterial stenosis (ICAS) is a non-marginal cause of stroke/transient ischemic attacks (TIAs) and is associated with high stroke recurrence rate. Some studies have investigated the best secondary prevention ranging from antithrombotic therapy to endovascular treatment (ET). However, no direct comparison between all the possible treatments is currently available especially between single and dual anti-platelet therapies (SAPT and DAPT). Aim: To establish whether DAPT is more effective than SAPT in preventing the recurrence of ICAS-related stroke, by means of a network meta-analysis (NMA). Design: Systematic review and NMA in accordance to PRISMA guidelines. Data sources and methods: We performed a systematic review of trials investigating secondary prevention (SAPT or DAPT, anticoagulant treatment or ET) in patients with symptomatic ICAS available in MEDLINE, Scopus and Web of Science from January 1989 to May 2021. We defined our primary efficacy outcome as the recurrence of ischemic stroke/TIA. We analysed the extracted data with Bayesian NMA approach. Results: We identified 815 studies and included 5 trials in the NMA. Sequence generation was adequate in all the selected studies while the allocation concealment method was described in one study. All the included studies reported the pre-specified primary outcomes, and outcome assessment was blinded in all the studies. We used the fixed-effect approach as the heterogeneity was not significant ( p > 0.1) according to the Cochran’s Q statistic. DAPT was superior to SAPT and DAPT + ET in preventing stroke/TIA recurrence [respectively, odds ratio (OR), 0.59; confidence interval (CI), 0.39–0.9; and OR, 0.49, CI, 0.26–0.88], while no difference was found between DAPT and oral anticoagulant therapy (OAC). DAPT was safer than OAC (OR, 0.48; CI, 0.26–0.89) and DAPT + ET (OR, 0.50; CI, 0.35–0.71), while no difference was found between DAPT and SAPT. Conclusion: DAPT is more effective than SAPT for secondary stroke prevention in patients with symptomatic ICAS, without increasing the risk of haemorrhage. Registration: Prospero/CRD42019140033.
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| 10. |
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| 11. |
- Talhada, Daniela, et al.
(author)
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The role of dopaminergic immune cell signalling in poststroke inflammation
- 2018
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In: Therapeutic Advances in Neurological Disorders. - : SAGE Publications. - 1756-2856 .- 1756-2864. ; 11
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Research review (peer-reviewed)abstract
- Upon ischaemic stroke, brain-resident and peripheral immune cells accumulate in the central nervous system (CNS). Interestingly, these cells express pattern specific to neurotransmitter receptors and, therefore, seem to be susceptible to neurotransmitter stimulation, potentially modulating their properties and functions. One of the principal neurotransmitters in the CNS, dopamine, is involved in the regulation of processes of brain development, motor control and higher brain functions. It is constantly released in the brain and there is experimental and clinical evidence that dopaminergic signalling is involved in recovery of lost neurological function after stroke. Independent studies have revealed specific but different patterns of dopamine receptor subtypes on different populations of immune cells. Those patterns are dependent on the activation status of cells. Generally, exposure to dopamine or dopamine receptor agonists decreases detrimental actions of immune cells. In contrast, a reduction of dopaminergic inputs perpetuates a pro-inflammatory state associated with increased release of pro-inflammatory molecules. In addition, subsets of immune cells have been identified to synthesize and release dopamine, suggesting autoregulatory mechanisms. Evidence supports that inflammatory processes activated following ischaemic stroke are modulated by dopaminergic signalling.
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| 12. |
- Virhammar, Johan, et al.
(author)
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Levodopa-carbidopa enteral suspension in advanced Parkinson's disease: clinical evidence and experience
- 2017
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In: Therapeutic advances in neurological disorders. - : SAGE Publications. - 1756-2856 .- 1756-2864. ; 10:3, s. 171-187
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Research review (peer-reviewed)abstract
- The duration of action of oral levodopa becomes shorter as Parkinson's disease (PD) progresses. Patients with advanced PD may develop potentially disabling motor fluctuations and abnormal involuntary movement (dyskinesia), which cannot be managed with optimized oral or transdermal PD medications. The progressively worsening symptoms can have a substantial impact on the patient quality of life (QoL). Levodopa-carbidopa intestinal gel (LCIG) is delivered continuously via a percutaneous endoscopic gastrostomy with a jejunal extension (PEG-J). LCIG is licensed for the treatment of levodopa-responsive advanced PD in individuals experiencing severe motor fluctuations and dyskinesia when available combinations of antiparkinsonian medications have not given satisfactory results. Initial evidence for the efficacy and tolerability of LCIG came from a number of small-scale studies, but recently, three prospective studies have provided higher quality evidence. A 12-week double-blind comparison of LCIG with standard levodopa therapy, a 52-week open-label study extension of the double-blind study, and a 54-week open-label safety study, demonstrated significant improvements in 'off' time and 'on' time without troublesome dyskinesia, and QoL measures that were maintained in the longer term. There are also observations that LCIG may be effective treatment for nonmotor symptoms (NMS) although the evidence is limited. There is a need for further research on the efficacy of LCIG in reducing NMS, dyskinesia and improving QoL. This review surveys the clinical evidence for the effectiveness and tolerability of LCIG in the management of advanced PD and highlights some practical considerations to help optimize treatment.
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| 13. |
- Woock, Malin, et al.
(author)
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Cancer and stroke: commonly encountered by clinicians, but little evidence to guide clinical approach.
- 2022
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In: Therapeutic advances in neurological disorders. - : SAGE Publications. - 1756-2856 .- 1756-2864. ; 15
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Journal article (peer-reviewed)abstract
- The association between stroke and cancer is well-established. Because of an aging population and longer survival rates, the frequency of synchronous stroke and cancer will become even more common. Different pathophysiologic mechanisms have been proposed how cancer or cancer treatment directly or via coagulation disturbances can mediate stroke. Increased serum levels of D-dimer, fibrin degradation products, and CRP are more often seen in stroke with concomitant cancer, and the clot retrieved during thrombectomy has a more fibrin- and platelet-rich constitution compared with that of atherosclerotic etiology. Multiple infarctions are more common in patients with active cancer compared with those without a cancer diagnosis. New MRI techniques may help in detecting typical patterns seen in the presence of a concomitant cancer. In ischemic stroke patients, a newly published cancer probability score can help clinicians in their decision-making when to suspect an underlying malignancy in a stroke patient and to start cancer-screening studies. Treating stroke patients with synchronous cancer can be a delicate matter. Limited evidence suggests that administration of intravenous thrombolysis appears safe in non-axial intracranial and non-metastatic cancer patients. Endovascular thrombectomy is probably rather safe in these patients, but probably futile in most patients placed on palliative care due to their advanced disease. In this topical review, we discuss the epidemiology, pathophysiology, and prognosis of ischemic and hemorrhagic strokes as well as cerebral venous thrombosis and concomitant cancer. We further summarize the current evidence on acute management and secondary preventive therapy.
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| 14. |
- Zelano, Johan, 1981
(author)
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Poststroke epilepsy: Update and future directions
- 2016
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In: Therapeutic Advances in Neurological Disorders. - : SAGE Publications. - 1756-2856 .- 1756-2864. ; 9:5, s. 424-435
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Journal article (peer-reviewed)abstract
- Stroke is among the most common causes of epilepsy after middle age. Patients with poststroke epilepsy (PSE) differ in several respects from patients with other forms of structural-metabolic epilepsy; not least in age, age-related sensitivity to side effects of antiepileptic drugs (AEDs), and specific drug-drug interaction issues related to secondary-stroke prophylaxis. Encouragingly, there has lately been remarkable activity in the study of PSE. Three developments in PSE research deserve particular focus. First, large prospective trials have established the incidence and risk factors of PSE in the setting of modern stroke care. Stroke severity, cortical location, young age, and haemorrhage remain the most important risk factors. Second, although more studies are needed, epidemiological data indicate that the risk of PSE may be influenced, for instance, by statin treatment. Third, studies are emerging regarding the treatment and prognosis of PSE. Levetiracetam and lamotrigine may be well tolerated treatment options and seizure freedom is achieved in at least a similar proportion of patients as in other epilepsies. Furthermore, new animal models such as photothrombotic stroke gives hope of a more clear understanding of PSE epileptogenesis in the near future. In summary, PSE shows indications of maturing into an independent epilepsy research field. This review summarizes recent advances in our understanding of PSE and provides an update on management issues such as diagnosis, AED selection, and prognosis. Finally, future research challenges in the field are outlined. © The Author(s), 2016.
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| 15. |
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| 16. |
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| 17. |
- Hagell, Peter, et al.
(author)
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The 39-Item Parkinson's Disease Questionnaire (PDQ-39) : is it a unidimensional construct?
- 2009
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In: Therapeutic advances in neurological disorders. - 1756-2856. ; 2:4, s. 205-214
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Journal article (peer-reviewed)abstract
- The 39-item Parkinson's Disease Questionnaire, and particularly its summary index (PDQ-39SI) is a widely used patient-reported clinical trial endpoint. A basic assumption when summing items into a total score is that they represent a common variable. We therefore assessed the unidimensionality of the PDQ-39SI using Rasch and confirmatory factor analysis. Both analyses showed model misfit. Adjustment for differential item functioning and disordered response category thresholds did not improve model fit, and residual analyses showed deviation from unidimensionality. These data indicate multidimensionality and challenge the interpretation and validity of PDQ-39SI scores. Clinicians and investigators should use and interpret the PDQ-39SI with caution.
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| 18. |
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| 19. |
- Nicholas, Richard, et al.
(author)
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The impact of healthcare systems on the clinical diagnosis and disease-modifying treatment usage in relapse-onset multiple sclerosis : a real-world perspective in five registries across Europe
- 2023
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In: Therapeutic advances in neurological disorders. - : SAGE Publications. - 1756-2856. ; 16
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Journal article (peer-reviewed)abstract
- Introduction: Prescribing guidance for disease-modifying treatment (DMT) in multiple sclerosis (MS) is centred on a clinical diagnosis of relapsing–remitting MS (RRMS). DMT prescription guidelines and monitoring vary across countries. Standardising the approach to diagnosis of disease course, for example, assigning RRMS or secondary progressive MS (SPMS) diagnoses, allows examination of the impact of health system characteristics on the stated clinical diagnosis and treatment access. Methods: We analysed registry data from six cohorts in five countries (Czech Republic, Denmark, Germany, Sweden and United Kingdom) on patients with an initial diagnosis of RRMS. We standardised our approach utilising a pre-existing algorithm (DecisionTree, DT) to determine patient diagnoses of RRMS or secondary progressive MS (SPMS). We identified five global drivers of DMT prescribing: Provision, Availability, Funding, Monitoring and Audit, data were analysed against these concepts using meta-analysis and univariate meta-regression. Results: In 64,235 patients, we found variations in DMT use between countries, with higher usage in RRMS and lower usage in SPMS, with correspondingly lower usage in the UK compared to other registers. Factors such as female gender (p = 0.041), increasing disability via Expanded Disability Status Scale (EDSS) score (p = 0.004), and the presence of monitoring (p = 0.029) in SPMS influenced the likelihood of receiving DMTs. Standardising the diagnosis revealed differences in reclassification rates from clinical RRMS to DT-SPMS, with Sweden having the lowest rate Sweden (Sweden 0.009, range: Denmark 0.103 – UK portal 0.311). Those with higher EDSS at index (p < 0.03) and female gender (p < 0.049) were more likely to be reclassified from RRMS to DT-SPMS. The study also explored the impact of diagnosis on DMT usage in clinical SPMS, finding that the prescribing environment and auditing practices affected access to treatment. Discussion: This highlights the importance of a healthcare system’s approach to verifying the clinical label of MS course in facilitating appropriate prescribing, with some flexibility allowed in uncertain cases to ensure continued access to treatment.
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| 20. |
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