Rio Score Research Articles

Prediction of disease activity and treatment failure in relapsing–remitting MS patients initiating daily oral DMTs

Background: Limited data exist regarding treatment response prediction to oral disease-modifying therapies (DMTs) in multiple sclerosis (MS). Objectives: We assessed the capacity of available scoring systems to anticipate disease activity parameters in naïve relapsing–remitting MS (RRMS) patients initiating daily oral DMTs, hypothesizing that they exhibit different predictive potentials. Methods: We conducted a retrospective study and applied the Rio Score (RS), modified Rio Score (mRS), and MAGNIMS Score 12 months after DMT initiation. At 36 months, we examined their ability to predict evidence of disease activity (EDA) components and treatment failure by logistic regression analysis. Results: Notably, 218 patients (62.4% females) initiating dimethyl fumarate, teriflunomide, and fingolimod were included. At 36 months, the RS high-risk group predicted evidence of clinical activity (odds ratio (OR) 10 [2.7–36.9]) and treatment failure (OR 10.6 [3.4–32.5]) but did not predict radiological activity (OR 1.9 [0.7–5]). The mRS non-responders group did not predict EDA and treatment failure. RS, mRS, and MAGNIMS 0 categories showed significantly lower EDA and treatment failure than the remainder. Conclusion: Scoring systems present different predictive abilities for disease activity parameters at 36 months in MS patients initiating daily oral therapies, warranting further adjustments (i.e. introduction of fluid biomarkers) to depict disease activity status fully.

Rurality index score and pediatric neuro-oncological outcome in Ontario.

Rapid access to neurosurgical decisions and definitive management are vital for the outcome of neurocritical patients. There are unique challenges associated with the provision of services required to maintain critical infrastructure for rural citizens. Given that a relationship between rurality, marginalization, and health outcomes has been identified as associated with higher mortality rates and higher rates of many diseases, the authors studied whether worse clinical outcomes were associated with rurality in pediatric neuro-oncological disease. Using linked administrative databases, the authors retrospectively analyzed a population-based cohort of patients diagnosed with a pediatric brain tumor between 1996 and 2017 in Ontario, Canada. The main variable of interest was the Rurality Index for Ontario (RIO; larger value denotes more rural); the main outcome was survival, while controlling for surgery and tumor type. Of the 1428 patients included, 53.9% were male. Overall survival of all the children (controlling for surgery and tumor type) at 1, 5, and 10 years was 84.7%, 65.1%, and 58.4%, respectively. A total of 11.5% were classified as living in a rural area of Ontario. The distance to the nearest pediatric neurosurgical hospital ranged from 25.6 to 167.4 km. The RIO score was 0 in 38.7% of children, and the majority of patients had a RIO score < 40. A higher RIO score was not a significant factor (continuous p = 0.12/ordinal p = 0.18) associated with length of follow-up, indicating that rurality was not significantly linked to compliance with clinical follow-up. Rurality of the region in which pediatric neuro-oncological patients reside was not associated with patient outcome (HR 0.83, p = 0.39).

GANAB as a Novel Biomarker in Multiple Sclerosis: Correlation with Neuroinflammation and IFI35.

Multiple sclerosis (MS) still lacks reliable biomarkers of neuroinflammation predictive for disease activity and treatment response. Thus, in a prospective study we assessed 55 MS patients (28 interferon (IFN)-treated, 10 treated with no-IFN therapies, 17 untreated) and 20 matched healthy controls (HCs) for the putative correlation of the densitometric expression of glucosidase II alpha subunit (GANAB) with clinical/paraclinical parameters and with interferon-induced protein 35 (IFI35). We also assessed the disease progression in terms of the Rio Score (RS) in order to distinguish the responder patients to IFN therapy (RS = 0) from the non-responder ones (RS ≥ 1). We found GANAB to be 2.51-fold downregulated in the IFN-treated group with respect to the untreated one (p < 0.0001) and 3.39-fold downregulated in responder patients compared to the non-responders (p < 0.0001). GANAB correlated directly with RS (r = 0.8088, p < 0.0001) and lesion load (LL) (r = 0.5824, p = 0.0014) in the IFN-treated group and inversely with disease duration (DD) (r = −0.6081, p = 0.0096) in the untreated one. Lower mean values were expressed for GANAB than IFI35 in IFN responder (p < 0.0001) and higher mean values in the non-responder patients (p = 0.0022). Inverse correlations were also expressed with IFI35 in the overall patient population (r = −0.6468, p < 0.0001). In conclusion, the modular expression of GANAB reflects IFI35, RS, DD, and LL values, making it a biomarker of neuroinflammation that is predictive for disease activity and treatment response in MS.

Treatment response scoring systems to assess long-term prognosis in self-injectable DMTs relapsing-remitting multiple sclerosis patients.

Different treatment response scoring systems in treated MS patients exist. The objective was to assess the long-term predictive value of these systems in RRMS patients treated with self-injectable DMTs. RRMS-treated patients underwent brain MRI before the onset of therapy and 12months thereafter, and neurological assessments every 6months. Clinical and demographic characteristics were collected at baseline. After the first year of treatment, several scoring systems [Rio score (RS), modified Rio score (MRS), MAGNIMS score (MS), and ROAD score (RoS)] were calculated. Cox-Regression and survival analyses were performed to identify scores predicting long-term disability. We included 319 RRMS patients. Survival analyses showed that patients with RS > 1 and RoS > 3 had a significant risk of reaching an EDSS of 4.0 and 6.0 The score with the best sensitivity (61%) was the RoS, while the MRS showed the best specificity (88%). The RS showed the best positive predictive value (42%) and the best accuracy (81%). The combined measures integrated into different scores have an acceptable prognostic value for identifying patients with long-term disability. Thus, these data reinforce the concept of early treatment optimization to minimize the risk of long-term disability.

Modified Rio Score with Platform Therapy Predicts Treatment Success with Fingolimod and Natalizumab in Relapsing-Remitting Multiple Sclerosis Patients.

Background: Reliable markers of disease outcomes in multiple sclerosis (MS) would help to predict the response to treatment in patients treated with high efficacy drugs. No evidence of disease activity (NEDA) has become a treatment goal whereas the modified Rio score (MRS) predicts future suboptimal responders to treatment. The aim of our study was to identify factors that would predict poor response to treatment with natalizumab and fingolimod. Methods: In the multicenter prospective trial, 336 subjects were enrolled, initiating therapy with natalizumab (n = 135) or fingolimod (n = 201). Data on relapse rate, the expanded disability status scale, and MRI results were collected, and MRS was estimated. Results: NEDA-3 after the first year of therapy was 73.9% for natalizumab and 54.8% for fingolimod (p < 0.0001). Patients with MRS = 0 in the last year on platform therapy had the best NEDA-3 (71%) and patients with MRS = 3 had the worst NEDA-3 (41%) in the first year of treatment with the second-line therapy. Conclusion: We conclude that switching to the second-line therapy should occur earlier to enable better results for patients treated with natalizumab or fingolimod. The outcome on both drugs is better with better neurological conditions and lower MRS of the patient on the platform therapy.

The use of Modified Rio score for determining treatment failure in patients with multiple sclerosis: retrospective descriptive case series study.

Predicting treatment failure and switching effective treatment immediately in patients with multiple sclerosis (MS) is important. We aimed to evaluate the usefulness of Modified Rio score (MRS) in predicting treatment failure in MS patients. This is a retrospective study, which was conducted in two University Hospital. 129 MS patients treated with İnterferon or glatiramer-acetate from 2 clinical sites, were retrospectively selected. MRS was calculated after the first year of therapy. Treatment failure was defined as the presence of a 1 point increase in EDSS, 2 clinical attacks, 1 clinical attack and progression, 1 clinical attack and new lesion on MRI except associated with an attack, or new lesion in 2 different MRI taken at least 3months apart. The sensitivity, specificity, positive and negative predictive values of the MRS in predicting treatment failure were determined. 71 (55%) patients with score '0', 41 (31.8%) patients with score '1', 11 (8.5%) patients with score '2', 6 (4.7%) patients with score '3' were detected. 14 patients needed treatment switching during the first three years of the treatment. Sensitivity was 57%, specificity was 92%, positive predictive value was 95%, negative predictive value was 47% and accuracy was 89%. Modified Rio score (MRS) was found to be effective in determining the treatment failure as mentioned before. This study will be useful for clinicians who evaluate the treatment failure like us, and this study revealed that the MRS may also help predict treatment failure.

IFI35 as a biomolecular marker of neuroinflammation and treatment response in multiple sclerosis

Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) with unpredictable clinical outcome. As such, there is an urgent need to identify biomarkers that can predict the treatment response. Therefore, in an open-label, clinical, paraclinical and molecular prospective study, we assessed 50 interferon (IFN) treated MS patients for Rio Score (RS)/Modified Rio Score (MRS) and densitometric expression of the interferon-induced protein 35 (IFI35), a signal-protein with potential to be clinically relevant in the management of the disease. We found 4.92-fold upregulated IFI35 in IFN-treated MS group respect to healthy controls (p < .0001) and 2.31-fold respect to untreated MS group (p < .0001). Moreover, IFI35 expression profile correlated with RS and MRS rank values (r = −0.6018, p < .0001; r = −0.620, p < .0001), white matter volume (r = −0.5041; p = .0017) and cerebral lesion load (r = −0.5075; p = .0026). Finally, the main proportion of IFN-treated MS patients non-reaching the 65% threshold in IFI35 expression leaved the RS/MRS rank value 0 in a period ranging from 5 to 15 months (p < .0001) from the study entry; instead, all patients that reaching this threshold maintained the RS/MRS value 0 until the study end (p < .0001). In conclusion, the expression level of IFI35 in untreated MS patients highlights a correlation with neuroinflammation. Furthermore, IFI35 expression in IFN-treated MS patients shows a modular correlation between dosing regimes, which is predictive for long-term clinical outcome and drug efficacy.

Second-Line Therapy in Multiple Sclerosis

Multiple sclerosis (MS) patients with breakthrough disease on immunomodulatory drugs are frequently offered to switch to second-line treatment (SLT). No head-to-head study has been performed yet to assess whether SLT is more effective than classical immunomodulators. We aim to retrospectively assess the moment of introduction, efficacity and tolerance of SLT. We retrospectively enrolled the patients in our department with relapsing-remitting MS (RRMS) who received first-line treatment (FLT) for more than 12 months than switched to SLT for 5 consecutive years. Outcome measures were Rio Score (RS) and modified Rio Score (MRS), annualized relapse rate (ARR) and changes in expanded disability status scale (EDSS) score. We also reported the side effects developed under SLT. We enrolled 20 patients, 6 males and 13 females. They all received interferon before switch. Twelve were switched to Natalizumab (NAT) and eight to Fingolimod (FIN). When switch was decided, 16 patients (80%) had high RS (2 or 3) and 19 (95%) had high MRS (2 or 3). Mean ARR was at 2.4 at the switch to SLT, it decreased significantly to 0.73 (70%) after 12 months and 0.4 (84%) after 5 years (p< 0.001). Nine patients were relapse-free after 12 months (75%) and 5 after 5 years (25%). Mean EDSS was at 3.36 at the switch to SLT, it significally decreased to 3 after 12 months and 1.5 after 5 years (p< 0.001). Side effects reported in 6 cases (30%); 3 cases of lymphopenia under FIN, 2 cases of lymphocytosis and on case of BK virus urinary infection under TYS. MRS was better to predict suboptimal interferon responders than RS in our study. SLT was more effective than interferon on disease progress and activity during the first 5 years of treatment. However, prospective head to head studies are needed to get higher evidence level.

The emerging role of serum zinc in motor disability and radiological findings in patients with multiple sclerosis

BackgroundThe role of serum Zinc in the pathogenesis of relapsing remittent multiple sclerosis (RRMS) and its impact on motor disability and radiological findings remains a matter of debate.ObjectivesTo assess the level of serum Zinc in patients with RRMS at time of relapse and during remission and to correlate serum zinc with degree of disability, fatigue, response to disease modifying drugs, and magnetic resonance imaging (MRI) findings.Subjects and methodsA case-control study was carried out on 75 subjects divided into three groups, 25 patients diagnosed as RRMS during relapse, 25 patients during remission, and 25 healthy controls. All included patients were subjected to neurological assessment including Expanded Disability Status Scale (EDSS), Modified fatigue impact scale (MFIS), and Modified RIO score (MRS). Zinc serum level was measured for all patients and controls using direct colorimetric test method. Brain and spine MRI were done for all included patients.ResultsMS patients in relapse and during remission were found to have significantly lower zinc level than the control group (P value = 0.001 and < 0.001 respectively). There was a statistically significant negative correlation between serum zinc level and disease duration, number of relapses in the last 2 years, total number of relapses, EDSS before and after pulse steroids, MRS, MFIS, and MRI lesion load (P value = 0.017, 0.037, 0.001, 0.001, 0.004, 0.005, and 0.001, respectively).ConclusionSerum zinc level is significantly lower in patients with MS than healthy controls. It is negatively correlated with disease duration, number of relapses, motor disability, fatigue, and MRI lesion load.

Variation in Access to Specialist Care and Risk of Surgery in Patients with Inflammatory Bowel Disease: A Population-Based Cohort Study

IntroductionInflammatory bowel disease (IBD; subtypes: Crohn’s disease (CD) and ulcerative colitis (UC)) is a chronic disease of the gastrointestinal tract with rising prevalence among people ≥65y. Rural residents, especially those ≥65y, have decreased access to specialist care. Specialist care is associated with lower risk of hospitalization and surgery.&#x0D; Objectives and ApproachWe evaluated variation across physician networks in access to specialist care and surgery among incident patients ≥65y in Ontario health administrative data. Access to specialist care was defined as: ≥1 outpatient visit to gastroenterologists or the majority of IBD-specific outpatient care by gastroenterologists. Variation was assessed with multilevel logistic regression and median odds ratios (MOR), adjusting for age, sex, distance from IBD physician, comorbidities, neighbourhood income, and rural/urban. Models evaluating surgical risk also adjusted for specialist care use, emergency department visits, and hospitalization at diagnosis. Network-level variables included rurality (RIO score), population colonoscopy and gastroenterologist supply.&#x0D; ResultsThere was significant variation in having ≥1 gastroenterologist visit (CD p=0.0001, MOR 3.3; UC p&lt;0.0001, MOR 3.1) and gastroenterologist providing the majority of care (CD p=0.0001, MOR 3.0; UC p&lt;0.0001, MOR 3.7) within 12 months of diagnosis. Variation remained significant after accounting for network-level characteristics (≥1 gastroenterologist visit: CD p=0.0002, MOR 2.6, UC p&lt;0.0001, MOR 2.2; majority of care: CD p=0.0002, MOR 2.4; UC p&lt;0.0001, MOR 2.4). In CD, there was no variation in the five-year risk of surgery (p=0.07, MOR 1.3) and was unchanged by network-level factors (p=0.13, MOR 1.3). Variation in the risk of colectomy exists for patients with UC (p=0.016, MOR 1.3) and was not reduced when accounting for network-level characteristics (p=0.019, MOR 1.3).&#x0D; Conclusion/ImplicationsAccess to specialist care among patients with elderly-onset IBD is varies greatly between networks but this variation cannot be explained by differing provision of gastroenterological services across physician networks. Further research is needed to understand the factors that influence access to care and outcomes in elderly patients with IBD.

The Matrix Metalloproteinases Panel in Multiple Sclerosis Patients Treated with Natalizumab: A Possible Answer to Natalizumab Non- Responders.

In the lymphocyte migration across the blood-brain barrier (BBB) in multiple sclerosis (MS), matrix metalloproteinases (MMPs) play an important role in the degradation of the basal membrane. Natalizumab (NAT), a monoclonal antibody, binds to the alpha-4 (α4) integrin leading to BBB impermeability. Approximately 30% of NAT-treated patients show clinical or MRI signs of BBB disruption. To determine whether NAT significantly influences the MMPs serum levels and to what extent these could be used as biomarkers in relapsing-remitting MS (RRMS) patients. This prospective study over a period of 8 months of NAT treatment, included 30 RRMS patients (mean age 38 ± 6 years; mean MS duration 12 ± 5 years), of which ten were initially naive to NAT and 15 were healthy controls. We determined the serum levels of the MMPs Panel (MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP12, and MMP13) quantified by a multiplex method at the beginning and end of the study. After 8 months of NAT treatment, a statistically significant decrease was found in MMP9, MMP2, MMP3, MMP8, and MMP10 levels. Relapses during the study were correlated with a variation of MMP12 and MMP13 serum levels. MMP9 had the most numerous correlations with the EDSS score, Rio score, and duration of NAT treatment. MMPs signature (the sum of all MMPs) and the MMP9/MMP2 ratio significantly decreased during the study. 1. The serum level of MMP9 significantly decreased by NAT treatment and correlates with MS activity; 2. After eight months of NAT treatment, the MMPs signature and the MMP9/MMP2 ratio decreased; 3. MMP9 might be used as a biomarker in MS patients treated with NAT.

Disability progression markers over 6–12 years in interferon-β-treated multiple sclerosis patients

Objective: To investigate the association between activity during interferon-beta (IFNβ) therapy and disability outcomes in patients with relapsing–remitting multiple sclerosis (RRMS). Methods: A longitudinal study based on two previously described cohorts of IFNβ-treated RRMS patients was conducted. Patients were classified according to clinical activity after 2 years (clinical cohort) or to clinical and radiological activity after 1 year (magnetic resonance imaging (MRI) cohort). Multivariate Cox models were calculated for early disease activity predicting long-term disability. Results: A total of 516 patients from two different cohorts were included in the analyses. Persistent clinical disease activity during the first 2 years of therapy predicted severe long-term disability (clinical cohort). In the MRI cohort, modified Rio score and no or minimal evidence of disease activity (NEDA/MEDA) did not identify patients with risk of Expanded Disability Status Scale (EDSS) worsening. However, a Rio score ≥ 2 (hazard ratio (HR): 3.3, 95% confidence interval (CI): 1.7–6.4); ≥3 new T2 lesions (HR: 2.9, 95% CI: 1.5–5.6); or ≥2 Gd-enhancing lesions (HR: 2.1, 95% CI: 1.1–4) were able to identify patients with EDSS worsening. Conclusion: Although early activity during IFNβ therapy is associated with poor long-term outcomes, minimal degree of activity does not seem to be predictive of EDSS worsening over 6.7-year mean follow-up.

Hypothalamic damage in multiple sclerosis correlates with disease activity, disability, depression, and fatigue

Objectives: Disturbances in the hypothalamo-pituitary axis are supposed to modulate activity of multiple sclerosis (MS). We hypothesised that the extent of HYP damage may determine severity of MS and may be associated with the disease evolution. We suggested fatigue and depression may depend on the degree of damage of the area.Method: 33 MS patients with relapsing-remitting and secondary progressive disease, and 24 age and sex-related healthy individuals (CON) underwent 1H-MR spectroscopy (1H-MRS) of the hypothalamus. Concentrations of glutamate + glutamin (Glx), cholin (Cho), myoinositol (mIns), N-acetyl aspartate (NAA) expressed as ratio with creatine (Cr) and NAA were correlated with markers of disease activity (RIO score), Multiple Sclerosis Severity Scale (MSSS), Depressive-Severity Status Scale and Simple Numerical Fatigue Scale.Results: Cho/Cr and NAA/Cr ratios were decreased and Glx/NAA ratio increased in MS patients vs CON. Glx/NAA, Glx/Cr, and mIns/NAA were significantly higher in active (RIO 1–2) vs non-active MS patients (RIO 0). Glx/NAA and Glx/Cr correlated with MSSS and fatigue score, and Glx/Cr with depressive score of MS patients. In CON, relationships between Glx/Cr and age, and Glx/NAA and fatigue score were inverse.Conclusion: Our study provides the first evidence about significant hypothalamic alterations correlating with clinical outcomes of MS, using 1H-MRS. The combination of increased Glu or mIns with reduced NAA in HYP reflects whole-brain activity of MS. In addition, excess of Glu is linked to severe disease course, depressive mood and fatigue in MS patients, suggesting superiority of Glu over other metabolites in determining MS burden.

Inflammatory Activity on Natalizumab Predicts Short-Term but Not Long-Term Disability in Multiple Sclerosis.

BackgroundIn people with multiple sclerosis treated with interferon-beta or glatiramer acetate, new MRI lesions and relapses during the first year of treatment predict a poor prognosis.ObjectiveTo study this association in those receiving natalizumab.MethodsData were collected on relapses, new MRI activity, and Modified Rio Score after initiation of natalizumab in an observational cohort of 161 patients with high baseline disability. These were correlated with Expanded Disability Status Scale (EDSS) progression at years 1, 2, 3, and 3–7 after treatment initiation, versus pre-treatment baseline.Results46/161 patients had a relapse in the first year and 44/161 had EDSS progression by year 2. Relapses and Modified Rio Score in the first year of treatment predicted EDSS progression at year 1 and 2 after treatment initiation. However, this effect disappeared with longer follow-up. Paradoxically, there was a trend towards inflammatory activity on treatment (first year Modified Rio Score, relapses, and MRI activity) predicting a lower risk of EDSS progression by years 3–7, although this did not reach statistical significance. Those with and without EDSS progression did not differ in baseline age, EDSS, or pre-treatment relapse rate. Relapses in year 0–1 predicted further relapses in years 1–3.ConclusionsBreakthrough inflammatory activity after natalizumab treatment is predictive of short-term outcome measures of relapses or EDSS progression, but does not predict longer term EDSS progression, in this cohort with high baseline disability.

Assessment of Interleukin-17A, Interleukin-10 and Transforming Growth Factor-Beta1 Serum Titers in Relapsing Remitting Multiple Sclerosis Patients Treated with Avonex, Possible Biomarkers for Treatment Response.

Individual response to interferon beta (IFN-β) 1a treatment is heterogeneous in multiple sclerosis (MS). Our objective was to find a connection between serum levels of interleukin (IL)-10, IL-17 and transforming growth factor beta (TGF-β)1 in MS patients treated with IFN-β in order to identify the nonresponders (NR). We included in the study 32 healthy subjects and 32 MS patients: 10 naive, 10 early treated and 12 late treated with INF-β1a. Serum determination of cytokines and brain MRI were performed at the beginning of the study, after 6 and 12 months. Rio score was calculated at the end of the study. MS patients had initially a significant higher level of IL-17 and a lower level of TGF-β1 compared to healthy subjects. IL-17 level in early treated patients was significantly lower compared to the naive and late treated groups. INF-β1a treatment significantly increased IL-10 and decreased IL-17 levels. Initial low levels of IL-10 were associated with an increase in physical disability. IL-17 levels positively correlated with the number of relapses and MRI activity. Nine patients were NR to Avonex. Patients with a Rio score of 3 had higher initial levels of IL-17 and those with a Rio score of 0 had higher initial levels of IL-10 and TGF-β1. IFN-β1a decreased IL-17 and increased IL-10 seric levels; IL-17 significantly correlated with MS activity; TGF-β1 activity is titer-dependent, increased levels were associated with IL-17 inhibition; NR patients to IFN-β1a will have initial high IL-17 and low IL-10 and TGF-β seric levels.

Predicting Treatment Response to Teriflunomide in the TEMSO Study Using the Modified Rio Score (P2.108)

Predicting Treatment Response to Teriflunomide in the TEMSO Study Using the Modified Rio Score (P2.108)

Respuesta al tratamiento con interferón beta en pacientes con esclerosis múltiple. Validación del Rio Score

Different criteria have been proposed for the response to treatment with interferon beta, and the Rio Score is one of the most widely used. The aim of this study was to validate the usefulness of the Rio Score in an independent cohort. A multi-centre, prospective, longitudinal study was conducted on patients with relapsing-remitting multiple sclerosis treated with interferon beta. The patients were classified according to the presence of attacks, active lesions (new in T2 or gadolinium enhancing lesions) in magnetic resonance imaging, a confirmed increase in disability or combinations of these variables (attacks, increase on the Expanded Disability Status Scale and active lesions) after one year's treatment. Regression analysis was used in order to identify the response-predicting variables after a three-year follow-up. The sample consisted of 249 patients with relapsing-remitting multiple sclerosis. The logistic model confirmed that the presence of two (odds ratio = 6.6; CI 95% = 2.7-16.1; p < 0.0001) or three (odds ratio = 8.5; CI 95% = 1.6-46; p < 0.01) positive variables during the first year of treatment were indicative of a significant risk of activity (attacks or progression) in the next two years. The usefulness of the Rio Score is confirmed, in an independent cohort, as a means of identifying patients with a higher risk of developing clinical activity or progression of disability during treatment with interferon beta.

Prediction of disability progression in fingolimod-treated patients

PurposeThe aim of the study was to evaluate whether early disease activity during fingolimod treatment could predict disease progression in patients with relapsing-remitting multiple sclerosis (RRMS). MethodsWe included RRMS patients who received fingolimod for at least 12months with a ≥36months of follow-up. Early disease activity was assessed by the modified Rio score (MRS). Association between MRS at 12months and time to disability progression over the following two years was assessed using Kaplan–Meier survival curves analysis and Cox proportional hazards model. ResultsAt 1year from starting treatment, 14 (58.3%), 5 (20.8%), 3 (12.5%) and 2 (8.3%) subjects had a MRS=0, 1, 2, and 3, respectively. The risk of disability progression in the next 2years was associated to the MRS and increased from 21.1% in patients with MRS=0–1 to 80% in those with MRS≥2 (adjusted HR=19.67; 95% CI=2.30–167.79; p=0.006). ConclusionsEarly disease activity is suggested to be associated with the risk of disease progression in patients receiving fingolimod and MRS could be a reliable tool to identify the subjects at higher risk of unfavorable course.

Utility of the rio score and modified rio score in korean patients with multiple sclerosis.

ObjectivesEarly identification of suboptimal responders to multiple sclerosis (MS) treatment is critical for optimizing therapeutic decisions. The Rio score (RS) and modified Rio score (MRS) were developed to discriminate the responses to interferon-beta (IFNB) treatment in MS patients. This study was performed to evaluate the utility of RS and MRS in daily clinical practice in Korea.MethodsThis was a real-world setting, multicenter, retrospective study of MS patients treated with IFNB from 10 hospitals in Korea. We investigated whether the RS and MRS at the early stage of IFNB therapy could predict treatment responses over 3 years. Suboptimal treatment responses at 3 years were defined as the presence of clinical relapse and/or EDSS progression and/or patients who had been treated with INFB for at least for 1 year and therapy was switched due to perceived treatment failure during the 2 years of follow-up.ResultsSeventy patients (50 females and 20 males) were enrolled; 92% (12/13) of patients with high RS and 86% (12/14) of patients with high MRS (score 2 or 3) were suboptimal responders, whereas 93% (53/57) of patients with low RS and 93% (52/56) patients with low MRS (score 0 or 1) showed optimal responses. New active lesions on MRI with clinical relapse in high RS and MRS were the most common combination in suboptimal responders.ConclusionsWe confirmed that RS and MRS at 6–15 months of IFNB therapy were useful for predicting poor responders over 3 years.

Validation of 1-year predictive score of long-term response to interferon-β in everyday clinical practice multiple sclerosis patients.

The Rio score (RS) and the modified Rio score (MRS) are two scoring systems that can identify the early predictive factors of disability progression in relapsing-remitting multiple sclerosis (RRMS) patients treated with interferon-β (IFN-β). The objective of the study was to validate the usefulness of the RS and MRS in a large cohort of multiple sclerosis patients treated with IFN-β in daily clinical practice. The analysis included a cohort of RRMS patients treated with different formulations of IFN-β for at least 1 year. The RS and MRS were used to classify the patients after 1 year of treatment. Multivariate analysis was performed to identify predictive variables of suboptimal response at 5 years, defined as Expanded Disability Status Scale confirmed progression or switching to a second-line therapy. Sixty-nine of 416 included patients were considered as suboptimal responders at 5-year evaluation. The possible score range was 0-3. A higher risk of suboptimal response was found for RS and MRS in the presence of ≥2 scores (hazard ratio 3.0, P = 0.002, and hazard ratio 5.0, P < 0.0001, respectively). Our study confirmed, in a daily clinical setting, that MRS had a better specificity and accuracy than RS in identifying the patients who will have a poor response to long-term IFN-β treatment.