Assessment of serum inflammatory parameters in RRMS and SPMS patients.

OBJECTIVES: Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease. Patients with relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) differ in their responses to treatment; therefore, the correct diagnosis of the particular type of MS is crucial, and biomarkers that can differentiate between the forms of MS need to be identified. The aim of this study was to compare the levels of inflammatory parameters in serum samples from patients with RRMS and SPMS. METHODS: The study group consisted of 60 patients with diagnosed MS. The patients were divided into RRMS and SPMS groups. In the RRMS patients, the usage of disease-modifying treatment was included in our analysis. The serum levels of inflammatory parameters were evaluated. RESULTS: The serum levels of BAFF, gp130 and osteopontin were significantly higher in SPMS patients than in RRMS patients. The serum levels of BAFF correlated with age in both RRMS and SPMS patients. The serum levels of MMP-2 were significantly higher in RRMS patients than in SPMS patients and correlated with the number of past relapses. The serum levels of IL-32 were significantly higher in RRMS treatment-naïve patients than in RRMS patients treated with disease-modifying therapy. DISCUSSION: Significant differences were found in BAFF, gp130, MMP-2 and osteopontin levels between RRMS and SPMS patients. Serum IL-32 levels were statistically lower in RRMS patients treated with disease-modifying therapy than in treatment-naïve patients.

Retinal small vessel pathology is associated with disease burden in multiple sclerosis.

BACKGROUND: Alterations of the superficial retinal vasculature are commonly observed in multiple sclerosis (MS) and can be visualized through optical coherence tomography angiography (OCTA). OBJECTIVES: This study aimed to examine changes in the retinal vasculature during MS and to integrate findings into current concepts of the underlying pathology. METHODS: In this cross-sectional study, including 259 relapsing-remitting MS patients and 78 healthy controls, we analyzed OCTAs using deep-learning-based segmentation algorithm tools. RESULTS: We identified a loss of small-sized vessels (diameter < 10 µm) in the superficial vascular complex in all MS eyes, irrespective of their optic neuritis (ON) history. This alteration was associated with MS disease burden and appears independent of retinal ganglion cell loss. In contrast, an observed reduction of medium-sized vessels (diameter 10-20 µm) was specific to eyes with a history of ON and was closely linked to ganglion cell atrophy. CONCLUSION: These findings suggest distinct atrophy patterns in retinal vessels in patients with MS. Further studies are necessary to investigate retinal vessel alterations and their underlying pathology in MS.

Passive assessment of tapping speed through smartphone is useful for monitoring multiple sclerosis.

INTRODUCTION: Continuously acquired smartphone keyboard interactions may be useful to monitor progression in multiple sclerosis (MS). We aimed to study the correlation between tapping speed (TS), measured as keys/s, and baseline disability scales in patients with MS. METHODS: Single-center prospective study in patients with MS. We passively assessed TS during first week, measured by an "in house" smartphone application. Reliability was assessed by intraclass correlation coefficient (ICC). Correlations between median and maximum keys/s of first week of assessment and baseline disability measures were explored. RESULTS: One-hundred three patients were included: 62.1 % women, with a median (IQR) age of 47 (40.4-54.8) years-old and an EDSS score of 3.0 (2.0-4.0). Distribution by MS subtypes was: 77.7 % relapsing-remitting MS (RRMS), 17.5 % secondary-progressive MS (SPMS) and 4.9 % primary-progressive MS (PPMS). ICC during first week was 0.714 (p < 0.00001). Both median and maximum keys/s showed a negative correlation with Expanded Disability Status Score, 9-hole peg test and timed 25-foot walk and a positive correlation with Processing Speed Test CogEval® raw and Z-score. Median and maximum keys/s were lower in patients diagnosed with SPMS than in RRMS. Both measures of tapping speed were associated with MS phenotype independently of age. CONCLUSION: TS measured through our application is reliable and correlates with baseline disability scales.

Cost avoidance from health system specialty pharmacist interventions in patients with multiple sclerosis.

BACKGROUND: Specialty pharmacists monitor patients taking multiple sclerosis (MS) disease-modifying therapies (DMTs) to evaluate response to therapy and intervene on adverse effects. These interventions have the potential to avoid health care costs by discontinuing inappropriate therapies and avoiding downstream health care utilization. OBJECTIVE: To calculate the costs avoided by specialty pharmacist interventions in MS. METHODS: A retrospective observational cohort study including patients at the Vanderbilt MS Clinic who received a specialty pharmacist intervention between February 1, 2022, and July 31, 2022, was performed. A panel of 3 investigators categorized each intervention based on the potential for cost avoidance: (1) no cost avoidance, (2) direct cost avoidance, and (3) indirect cost avoidance. A single intervention may have one or both cost avoidance types. Direct costs avoided included the cost of the potential service or medication avoided due to the intervention. Medication costs were calculated using the range of the average wholesale price and average wholesale price - 20%. For indirect costs avoided, the range of costs of a consequence (self-care, ambulatory visit, emergency department visit, hospitalization, or death) occurring had the intervention not been performed were multiplied by the range of probabilities for the consequence occurring (from zero [0] to very likely [0.5]). Self-care indirect cost savings equated to $0. Descriptive statistics summarized types of pharmacist interventions, the patients impacted, and costs avoided. In patients with an intervention that resulted in cost avoidance, chart review was performed to collect patient demographics, disease history, and MS-related health care usage during the 12 months prior to the pharmacist intervention. RESULTS: 485 pharmacist interventions in 354 individual patients were included. Fifty interventions in 38 individual patients (76% female, median age 51 years, 68% White) resulted in cost avoidance. The total estimated costs avoided in 6 months ranged from $123,733 to $156,265. In total, $138,410 were direct costs and $1,890 were indirect costs. Reasons for direct costs avoided (n = 13) were often safety monitoring (69%) or common side effects management (23%). Indirect costs avoidance (n = 37) resulted primarily from interventions on common side effects management (57%) and safety monitoring (22%). Self-care was the most common type of indirect cost avoided (n = 27). Interventions resulting in costs avoided were commonly seen in patients with relapsing-remitting MS (82%). The median time from MS diagnosis was 15 years and 42% of patients had previously trialed 1 other MS DMT. CONCLUSIONS: There is a potential for significant health care savings after specialty pharmacist interventions in MS, primarily from preventing the dispensing of inappropriate therapies.

Real-World Healthcare Cost Savings and Reduced Relapse Rate with Off-Label Rituximab versus Disease-Modifying Treatments Approved for Relapsing-Remitting Multiple Sclerosis: A Nationwide Cost-Effectiveness Study.

OBJECTIVE: Although off-label use of rituximab is a common alternative to disease-modifying therapies (DMTs) approved for multiple sclerosis (MS) in several countries, the impact of this on treatment cost-effectiveness is not well known. METHODS: We evaluated the relative cost-effectiveness of rituximab and MS-approved DMTs in a register-based cohort study of Swedish residents with relapsing-remitting MS, aged 18-65 years, starting treatment with rituximab, natalizumab, fingolimod, or dimethyl fumarate between January 2010 and July 2016, and followed through July 2021 (n = 5,924). By linking the population-based Swedish MS register to several Swedish health care and demographic registers, we estimated health care costs in relation to number of relapses, over 5 years from treatment start. Differences between treatments were estimated in inverse probability of treatment-weighted regression models, adjusting for a broad range of potential confounders covering demographics, medical history, and MS-related clinical characteristics. RESULTS: Off-label rituximab was associated with both lower total health care costs (mean cost savings ranged $35,000-$66,000 vs. each approved DMT), and fewer relapses (mean number of prevented relapses ranged 0.12-0.22), per started therapy over 5 years. Results were robust to variations in discounting and pricing of health care visits, with the main driver of cost-savings being the price of the index drug itself. INTERPRETATION: The cost-effectiveness of rituximab dominated the MS-approved alternatives. Off-label, low-dose rituximab should be considered for persons with MS and could reduce barriers to treatment, especially in resource-limited settings. ANN NEUROL 2024;95:1099-1111.

Burden of treatment and quality of life in relapsing remitting multiple sclerosis patients under early high efficacy therapy in Argentina: Data from the Argentinean registry.

The objective of this study was to describe and compare the burden of treatment (BOT) and the quality of life (QoL) in early high efficacy therapy (HET) vs. escalation therapy in relapsing remitting multiple sclerosis (RRMS) patients included in RelevarEM, the Argentinean registry of MS (RelevarEM, NCT 03,375,177). METHODS: cross sectional study conducted between September and December 2022. Participating patients were adults, RRMS patients who initiated (during the last three years) their treatment with a HET (natalizumab, ocrelizumab, alemtuzumab, cladribine) or with escalation treatment (beta interferon, glatiramer acetate, teriflunomide, dimethyl fumarate or fingolimod). Clinical and demographic aspect were collected. QoL and BOT was measured with the validated to Spanish MusiQol and BOT questionnaire. Propensity score (PS)-based nearest-neighbor matching was applied to homogenize groups. Comparisons were be done using a linear regression analysis model stratified by matched pairs, with BOT and QoL assessments as main outcomes. RESULTS: 269 patients were included in the analysis, mean age 33.7 ± 5.7 years, 193 (71.7 %) were female. A total of 136 patients were on early HET while 133 were on escalation therapy. In the entire group the mean total BOT score (±SD) was 48.5 ± 15.3 while in the group of patients receiving early HET we observed that the mean BOT score (±SD) was 43.5 ± 12.2 vs. 54.3 ± 13.3 in escalation treatment (p < 0.0001). Regarding the score QoL (±SD), in the entire sample we observed a global score of 77.4 ± 11.2. When we stratified groups, in HET (±SD) it was 81.3 ± 14 vs. 74.1 ± 18.3 in escalation therapy (p = 0.0003). CONCLUSION: in this multicenter study that included 269 patients from Argentina we observed in early HET a significantly lower BOT and higher QoL than patients receiving escalation therapy.

Healthcare utilization and costs associated with autologous haematopoietic stem cell transplantation in Norwegian patients with relapsing remitting multiple sclerosis.

Multiple sclerosis (MS) patients experience long-term deterioration of neurological function, reduced quality of life, long-lasting treatment cycles, and an increased risk of early workability loss imposing an economic burden to society. Autologous haematopoietic stem cell transplantation (AHSCT) has shown promising treatment effects for relapsing remitting MS (RRMS). This study employs a micro-costing approach to estimate healthcare utilization and costs associated with AHSCT in Norwegian RRMS patients. Patient-level data were extracted from medical journals of 30 RRMS patients receiving AHSCT treatment at Haukeland University Hospital in the period from January 2015 to January 2018. The time horizon for the analysis was from the pretransplant screening until one year after AHSCT. A correlation was found between patient body weight and total healthcare cost. The average total healthcare cost of AHSCT for RRMS patients was estimated to EUR 66 304 (95% CI: EUR 63 598 - EUR 69 010) including costs associated with the pre-AHSCT period, AHSCT treatment phases and one-year follow-up. The majority of the costs, EUR 64 329, occurred during the treatment phase and within the first 100 days after AHSCT. The results indicate that long-term healthcare cost savings may be achieved using AHSCT in selected patients with aggressive RRMS. This is due to the high costs of most used disease modifying treatments. Further research including long-term clinical data is needed to determine the cost-effectiveness of this treatment.

A US payer perspective health economic model assessing value of monitoring disease activity to inform discontinuation and re-initiation of DMT in multiple sclerosis.

OBJECTIVES: We evaluate the potential clinical and cost impacts of discontinuing disease-modifying therapy (DMT) in people with multiple sclerosis (PwMS) when age-related immunosenescence can reduce DMT efficacy while increasing associated risks. METHODS: A Markov model simulated clinical and cost impacts to the patient and payers when a proportion of eligible patients with relapsing remitting multiple sclerosis (RRMS) discontinue DMT. Eligibility was defined as age >55 years, an RRMS diagnosis of >5 years, and no history of relapses for 5 years. Increasing the proportion of eligible patients willing to discontinue therapy was also modeled. Clinical and cost inputs were from published literature. RESULTS: Difference in EDSS progression between eligible patients who did and did not attempt discontinuation was not significant. After 1 year of eligibility, per-patient costs were $96k lower in the cohort that attempted discontinuation; however a higher proportion of relapses were seen in this group. When the proportion of patients willing to discontinue DMT increased, clinical findings remained consistent while the average cost per patient decreased. CONCLUSION: While there are increased clinical and cost benefits as more eligible patients attempt discontinuation, the risk of relapses can increase. Timely disease monitoring is required to manage safe DMT discontinuation.

Comparative effectiveness and cost-effectiveness of natalizumab and fingolimod in rapidly evolving severe relapsing-remitting multiple sclerosis in the United Kingdom.

AIM: To evaluate the real-world comparative effectiveness and the cost-effectiveness, from a UK National Health Service perspective, of natalizumab versus fingolimod in patients with rapidly evolving severe relapsing-remitting multiple sclerosis (RES-RRMS). METHODS: Real-world data from the MSBase Registry were obtained for patients with RES-RRMS who were previously either naive to disease-modifying therapies or had been treated with interferon-based therapies, glatiramer acetate, dimethyl fumarate, or teriflunomide (collectively known as BRACETD). Matched cohorts were selected by 3-way multinomial propensity score matching, and the annualized relapse rate (ARR) and 6-month-confirmed disability worsening (CDW6M) and improvement (CDI6M) were compared between treatment groups. Comparative effectiveness results were used in a cost-effectiveness model comparing natalizumab and fingolimod, using an established Markov structure over a lifetime horizon with health states based on the Expanded Disability Status Scale. Additional model data sources included the UK MS Survey 2015, published literature, and publicly available sources. RESULTS: In the comparative effectiveness analysis, we found a significantly lower ARR for patients starting natalizumab compared with fingolimod (rate ratio [RR] = 0.65; 95% confidence interval [CI], 0.57-0.73) or BRACETD (RR = 0.46; 95% CI, 0.42-0.53). Similarly, CDI6M was higher for patients starting natalizumab compared with fingolimod (hazard ratio [HR] = 1.25; 95% CI, 1.01-1.55) and BRACETD (HR = 1.46; 95% CI, 1.16-1.85). In patients starting fingolimod, we found a lower ARR (RR = 0.72; 95% CI, 0.65-0.80) compared with starting BRACETD, but no difference in CDI6M (HR = 1.17; 95% CI, 0.91-1.50). Differences in CDW6M were not found between the treatment groups. In the base-case cost-effectiveness analysis, natalizumab dominated fingolimod (0.302 higher quality-adjusted life-years [QALYs] and £17,141 lower predicted lifetime costs). Similar cost-effectiveness results were observed across sensitivity analyses. CONCLUSIONS: This MSBase Registry analysis suggests that natalizumab improves clinical outcomes when compared with fingolimod, which translates to higher QALYs and lower costs in UK patients with RES-RRMS.

There are several medications used to treat people with relapsing remitting multiple sclerosis, such as interferon-based therapies (Betaferon/Betaseron (US), Rebif, Avonex, Extavia), glatiramer acetate (Copaxone), teriflunomide (Aubagio), and dimethyl fumarate (Tecfidera), collectively named BRACETD. Other treatments for multiple sclerosis (MS) have a narrower use, such as natalizumab (Tysabri) or fingolimod (Gilenya), among others.This study objective was to assess how well natalizumab and fingolimod helped treating MS (clinical effectiveness) and subsequently estimate what the cost of these treatments is in comparison to the benefit they bring to people with rapidly evolving severe MS that use them in the United Kingdom (UK) (cost-effectiveness).We used an international disease registry (MSBase), which collects clinical data from people with MS in various centers around the world to compare the effectiveness of natalizumab, fingolimod and BRACETD treatments. We used a technique called propensity score matching to obtain results from comparable patient groups. People treated with natalizumab had better disease control, namely with fewer relapses and higher improvement on their disability level, than patients on fingolimod or BRACETD. Conversely, there were no differences between each group of people on a measure called disability worsening.Based on these clinical results, we built an economic model that simulates the lifetime costs and consequences of treating people with MS with natalizumab in comparison with fingolimod. We found that using natalizumab was less costly and was more effective compared to using fingolimod in UK patients.

A multiscale assessment of bowel impairment in an Italian multiple sclerosis cohort.

Bowel dysfunctions (BD) in multiple sclerosis (MS) are under reported despite their clinical relevance. Scales usually applied do not thoroughly assess constipation and fecal incontinence. Instead, a proper qualitative and quantitative description of these symptoms might have relevant clinical and scientific consequences. The aim of this project is to study the prevalence of BD in a cohort of persons with MS (pwMS). Four-hundred and forty-seven pwMS (330 relapsing-remitting MS-RRMS and 117 progressive MS-PMS) were recruited. Three different questionnaires were administered: the neurogenic bowel dysfunction score (NBDS), the Wexner constipation scale (WexCon) and the Wexner incontinence scale (WexInc). All the scales were divided in subscores according to symptom severity. The prevalence of BD, considered as NBDS > 0, was 53.7%. Mean scores in pwMS group were as follows: NBDS 2.6 (SD 3.5), WexInc 1.1 (SD 2.4), WexCon 4.4 (SD 5.9). NBDS, WexCon and WexInc were significantly higher in PMS vs RRMS (p < 0.001), and significantly associated with disease duration, EDSS, multiple sclerosis severity score (p < 0.001), as well as with each other (p < 0.001). Our study confirms the presence of bowel dysfunctions in a large group of pwMS with a wide range of disability and their association with progressive disease phenotype and clinical disability.

Benefits of sphingosine-1-phosphate receptor modulators in relapsing MS estimated with a treatment sequence model.

BACKGROUND: Three sphingosine-1-phosphate receptor (S1PR) modulators are currently available as disease-modifying therapies (DMTs) for relapsing MS in the Netherlands (i.e. fingolimod, ozanimod and ponesimod). We aimed to identify which S1PR modulator yields the highest benefit from a health-economic and societal perspective during a patient's lifespan. METHODS: Incorporating Dutch DMT list prices, we used the ErasmusMC/iMTA MS model to compare DMT sequences, including S1PR modulators and eight other DMT classes, for treatment-naïve patients with relapsing MS in terms of health outcomes (number of lifetime relapses, time to Expanded Disability Status Scale (EDSS) 6, lifetime quality-adjusted life years (QALYs)) and cost-effectiveness (net health benefit (NHB)). We estimated the influence of list price and EDSS progression on cost-effectiveness outcomes. RESULTS: In deterministic and probabilistic analysis, DMT sequences with ponesimod have lower lifetime costs and higher QALYs resulting in a higher average NHB compared to sequences with other S1PR modulators. Ponesimod remains the most cost-effective S1PR modulator when EDSS progression is class-averaged. Given the variable effects on disability progression, list price reductions could make fingolimod but not ozanimod more cost-effective than ponesimod. CONCLUSION: Our model favours ponesimod among the S1PR modulators for the treatment of relapsing MS. This implies that prioritizing ponesimod over other S1PR modulators translates into a more efficacious spending of national healthcare budget without reducing benefit for people with MS. Prioritizing cost-effective choices when counselling patients contributes to affordable and accessible MS care.

[Assessment of the efficacy and safety of alemtuzumab in patients with highly active relapsing-remitting multiple sclerosis in Russian population]. / Otsenka effektivnosti i bezopasnosti alemtuzumaba u patsientov s vysokoaktivnym techeniem rasseyannogo skleroza v rossiiskoi populyatsii.

OBJECTIVE: To evaluate the severity and frequency of infusion reactions (IR) in patients with highly active relapsing-remitting multiple sclerosis (MS) In Russian population receiving alemtuzumab therapy. MATERIAL AND METHODS: In retrospective study, we analyzed data from 50 patients with highly active relapsing-remitting multiple sclerosis (MS) from six Regional MS Centers in the Russian Federation who received two courses of alemtuzumab between 2018 and 2022. RESULTS: Among all IRs, the most frequently reported were hives-like rashes, which were registered in 27 people, mostly of mild severity (70.6%). Headaches were the second most common IR, observed in 17 patients (34%). When comparing the group of patients who underwent music therapy (MT) with those who received alemtuzumab therapy without MT, no statistically significant difference was found in the frequency and severity of IRs. CONCLUSION: All patients experienced IRs of varying degrees of severity. A decrease in the score on the EDSS disability scale was noted. MT did not affect the occurrence or severity of IRs.

Rituximab for the treatment of relapsing-remitting multiple sclerosis in Thailand: an economic evaluation and budget impact analysis.

BACKGROUND: Multiple sclerosis is an inflammatory demyelination process in the central nervous system (CNS) causing neurological disability and poor quality of life. Currently, Thai Food and Drug Administration (FDA)-approved disease-modifying therapy is costly, and most patients with multiple sclerosis are ineligible for treatment in Thailand as previous studies have challenged its cost-effectiveness. Off-label use of rituximab is inexpensive and highly effective in treating multiple sclerosis, but evidence of its cost-effectiveness in Thailand is yet to be collected. METHODS: This study aimed to evaluate the cost-utility and budget impact of rituximab for multiple sclerosis treatment compared with best supportive care, the standard practice in Thailand to treat the disease. A Markov model with a one-month cycle length and lifetime horizon was applied to compare the costs and outcomes of rituximab and best supportive care based on a societal perspective. Accordingly, incremental cost-effectiveness ratios were estimated. Probabilistic and one-way sensitivity analyses were conducted to investigate parameter uncertainty. In addition, the Markov model was used to assess the 5-year budget impact from the government perspective. RESULTS: A rituximab biosimilar demonstrated higher effectiveness and lower associated costs, compared to best supportive care, with the highest probability of being cost-effective (96%). The probability of relapse was the most sensitive parameter according to the one-way sensitivity analysis. The calculated budget impact of treating patients with multiple sclerosis in Thailand was 26,360,000 Thai baht (THB) or 844,255 United States dollars (USD) in the first fiscal year, and approximately 20,810,000-23,080,000 THB (666,608-739,388 USD) in the next four fiscal years. CONCLUSION: In Thailand, a rituximab biosimilar would reduce the overall costs of multiple sclerosis treatment and should, therefore, be included in the National List of Essential Medicines.

Cost-consequence analysis of ofatumumab for the treatment of relapsing-remitting multiple sclerosis in Canada.

Aim: The costs and consequences of initial and delayed ofatumumab treatment were evaluated in relapsing-remitting multiple sclerosis with active disease in Canada. Materials & methods: A Markov cohort model was used (10-year horizon, annual cycle length, 1.5% discounting). Scenario analyses examined ofatumumab as first-line treatment versus 3 and 5 years following switch from commonly used first-line therapies. Results: Ofatumumab resulted in improvements in clinical outcomes (relapses and disease progression) and productivity (employment and full-time work), and reduction of economic burden (administration, monitoring and non-drug costs) that were comparable to other high-efficacy therapies (ocrelizumab, cladribine and natalizumab). Switching to ofatumumab earlier in the disease course may improve these outcomes. Conclusion: Results highlight the value of a high-efficacy therapy such as ofatumumab as initial treatment (i.e., first-line) in newly diagnosed relapsing-remitting multiple sclerosis patients with active disease.

Assessment of adherence to, and persistence with, an electromechanical autoinjector for subcutaneous interferon beta-1a injections for multiple sclerosis treatment over 3 years.

BACKGROUND: Self-administration of subcutaneous interferon beta-1a (sc IFN ß-1a) can be achieved with the RebiSmart® electromechanical autoinjector. This study investigated adherence to, and duration of persistence with, the newest version of the device (v1.6) among 2644 people receiving sc IFN ß-1a for multiple sclerosis (MS). RESEARCH DESIGN AND METHODS: This retrospective, observational study utilized data from RebiSmart® devices, recorded on the MSdialog database, between January 2014 and November 2019. Adherence and persistence were evaluated over a 3-year period and assessed in relation to age, sex, injection type, and injection depth. RESULTS: The population of RebiSmart® users (N = 2644) comprised of 1826 (69.1%) females and mean age was 39 (range 16-83) years. Adherence to RebiSmart® use and data transfer to the MSdialog database was consistently high (mean 91.7%; range 86.8-92.6%), including across all variables (81.6-100%). Mean (±SD) persistence during the study period was 1.35 ± 1.06 years, with a maximum recorded persistence of 5.1 years. In multivariate analysis, the longest durations of persistence were observed among older individuals and males (p < 0.0001 and p = 0.0078, respectively). CONCLUSIONS: People living with MS were highly adherent to use of the RebiSmart® device, with higher persistence generally observed for older and/or male individuals.

It is important for people living with multiple sclerosis (MS) to take their medication regularly ­ and to keep doing so ­ in order to control their symptoms. Some people with MS receive a medication called interferon beta-1a (Rebif®) as a subcutaneous injection (given just under the skin), and the RebiSmart® electromechanical autoinjector was designed to help them to self-inject such medication. This study aimed to find out whether people were using the RebiSmart® device as often as they should be, and how long they continued to use it for. Information was taken from the MSdialog database, which recorded peoples' use of the RebiSmart® device between January 2014 and November 2019. Records for 2644 people using the device were analyzed. Results showed that the RebiSmart® device was used most of the time (around 91.7%). On average, people kept using the device for around a year and 4 months before stopping. This duration was generally longer for men compared with women, and longer for older people than younger people. These results increase our understanding of how people are using the RebiSmart® device to treat their MS symptoms.

Clinical and economic evaluations of natalizumab, rituximab, and ocrelizumab for the management of relapsing-remitting multiple sclerosis in Saudi Arabia.

INTRODUCTION: The advent of new disease-modifying therapies (DMTs), such as monoclonal antibodies (mAbs), resulted in significant changes in the treatment guidelines for Multiple sclerosis (MS) and improvement in the clinical outcomes. However, mAbs, such as rituximab, natalizumab, and ocrelizumab, are expensive with variable effectiveness rates. Thus, the present study aimed to compare the direct medical cost and consequences (e.g., clinical relapse, disability progression, and new MRI lesions) between rituximab and natalizumab in managing relapsing-remitting multiple sclerosis (RRMS) in Saudi Arabia. Also, the study aimed to explore the cost and consequence of ocrelizumab in managing RRMS as a second-choice treatment. METHODS: The electronic medical records (EMRs) of patients with RRMS were retrospectively reviewed to retrieve the patients' baseline characteristics and disease progression from two tertiary care centers in Riyadh, Saudi Arabia. Biologic-naïve patients treated with rituximab or natalizumab or those switched to ocrelizumab and treated for at least six months were included in the study. The effectiveness rate was defined as no evidence of disease activity (NEDA-3) (i.e., absence of new T2 or T1 gadolinium (Gd) lesions as demonstrated by the Magnetic Resonance Imaging (MRI), disability progression, and clinical relapses), while the direct medical costs were estimated based on the utilization of healthcare resources. In addition, bootstrapping with 10,000 replications and inverse probability weighting based on propensity score were conducted. RESULTS: Ninety-three patients met the inclusion criteria and were included in the analysis (natalizumab (n = 50), rituximab (n = 26), ocrelizumab (n = 17)). Most of the patients were otherwise healthy (81.72%), under 35 years of age (76.34%), females (61.29%), and on the same mAb for more than one year (83.87%). The mean effectiveness rates for natalizumab, rituximab, and ocrelizumab were 72.00%, 76.92%, and 58.83%, respectively. Natalizumab mean incremental cost compared to rituximab was $35,383 (95% CI: $25,401.09- $49,717.92), and its mean effectiveness rate was 4.92% lower than rituximab (95% CI: -30-27.5) with 59.41% confidence level that rituximab will be dominant. CONCLUSIONS: Rituximab seems to be more effective and is less costly than natalizumab in the management of RRMS. Ocrelizumab does not seem to slow the rates of disease progression among patients previously treated with natalizumab.

Evaluation of risk management in a natalizumab home infusion procedure.

Natalizumab is a well-established disease-modifying therapy used in active multiple sclerosis (MS). The most serious adverse event is progressive multifocal leukoencephalopathy. For safety reasons, hospital implementation is mandatory. The SARS-CoV-2 pandemic has deeply affected hospital practices leading French authorities to temporarily authorize to administer the treatment at home. The safety of natalizumab home administration should be assessed to allow ongoing home infusion. The aim of the study is to describe the procedure and assess the safety in a home infusion natalizumab model. Patients presenting relapsing-remitting MS treated by natalizumab for over two years, non-exposed to John Cunningham Virus (JCV) and living in the Lille area (France) were included from July 2020 to February 2021 to receive natalizumab infusion at home every four weeks for 12 months. Teleconsultation occurrence, infusion occurrence, infusion cancelling, JCV risk management, annual MRI completion were analyzed. The number of teleconsultations allowing infusion was 365 (37 patients included in the analysis), all home infusions were preceded by a teleconsultation. Nine patients did not complete the one-year home infusion follow-up. Two teleconsultations canceled infusions. Two teleconsultations led to a hospital visit to assess a potential relapse. No severe adverse event was reported. All 28 patients who have completed the follow-up benefited from biannual hospital examination and JCV serologies and annual MRI. Our results suggested that the established home natalizumab procedure was safe using the university hospital home-care department. However, the procedure should be evaluated using home-based services outside the university hospital.

Disease-modifying therapies and cost-of-illness progression among people newly diagnosed with multiple sclerosis: a national register-based cohort study covering treatment initiation with interferons, glatiramer acetate or natalizumab.

OBJECTIVES: Disease-modifying therapies (DMTs) can slow disease progression in multiple sclerosis (MS). The objective of this study was to explore the cost-of-illness (COI) progression among newly diagnosed people with MS in relation to the first DMT received. DESIGN AND SETTING: A cohort study using data from nationwide registers in Sweden. PARTICIPANTS: People with MS (PwMS) in Sweden first diagnosed in 2006-2015, when aged 20-55, receiving first-line therapy with interferons (IFN), glatiramer acetate (GA) or natalizumab (NAT). They were followed up through 2016. OUTCOME MEASURES: Outcomes (in Euros, €) were: (1) secondary healthcare costs: specialised outpatient and inpatient care including out-of-pocket expenditure, DMTs including hospital-administered MS therapies, and prescribed drugs, and (2) productivity losses: sickness absence and disability pension. Descriptive statistics and Poisson regression were computed, adjusting for disability progression using the Expanded Disability Status Scale. RESULTS: 3673 newly diagnosed PwMS who were treated with IFN (N=2696), GA (N=441) or NAT (N=536) were identified. Healthcare costs were similar for the INF and GA groups, while the NAT group had higher costs (p value<0.05), owing to DMT and outpatient costs. IFN had lower productivity losses than NAT and GA (p value>0.05), driven by fewer sickness absence days. NAT had a trend towards lower disability pension costs compared with GA (p value>0.05). CONCLUSIONS: Similar trends over time for healthcare costs and productivity losses were identified across the DMT subgroups. PwMS on NAT maintained their work capacity for a longer time compared with those on GA, potentially leading to lower disability pension costs over time. COI serves as an objective measure to explore the importance of DMTs in maintaining low levels of progression of MS over time.