Measures in the first year of therapy predict the response to interferon β in MS

2009 ◽  
Vol 15 (7) ◽  
pp. 848-853 ◽  
Author(s):  
J Río ◽  
J Castilló ◽  
A Rovira ◽  
M Tintoré ◽  
J Sastre-Garriga ◽  
...  
Keyword(s):  
Disease Activity ◽  
Logistic Model ◽  
First Year ◽  
Interferon Β ◽  
Clinical Predictors ◽  
Predictors Of Response ◽  
Relapsing Remitting ◽  
Magnetic Resonance Imaging Mri ◽  
Relapsing Remitting Multiple Sclerosis

Background and objective Several criteria for treatment response to interferon beta (IFNβ) have been proposed, although there is no consensus among different investigators. Hence, the aim of this study was to investigate magnetic resonance imaging (MRI) and clinical predictors of response during the first 12 months of therapy. Methods This is a prospective and longitudinal study of relapsing-remitting multiple sclerosis (RRMS) patients treated with IFNβ. Patients were classified based on the presence of new lesions on MRI, relapses, confirmed disability increase, or combinations of all these variables after 1 year of therapy. Regression analysis was performed in order to identify variables of response after a follow-up of 3 years. Results We included 222 RRMS patients. The logistic model demonstrated that only the combination of new active lesions on MRI with the presence of relapses (OR 4.4; 95% CI 1.6–12.5) or disability progression (Odds Ratio (OR) 7.1; 95% Confidence Interval (CI) 1.6–33.9), or both (OR 6.5; 95% CI 1.9–23.4) achieved significant values to identify those patients with a poor outcome. Conclusions In RRMS patients treated with IFNβ, the combination of measures of disease activity and the presence of new active lesions on MRI may have a prognostic value for identifying patients with disease activity in the second and third year of therapy.

Efficacy of rituximab in refractory RRMS

2018 ◽  
Vol 25 (6) ◽  
pp. 828-836 ◽  
Author(s):  
Pierre Durozard ◽  
Adil Maarouf ◽  
Clémence Boutiere ◽  
Aurelie Ruet ◽  
Bruno Brochet ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Rescue Therapy ◽  
Outcome Data ◽  
Disease Modifying Therapy ◽  
Relapsing Remitting ◽  
Magnetic Resonance Imaging Mri ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Retrospective Multicenter Study

Objective: To investigate the efficacy of rituximab as rescue therapy in patients with relapsing-remitting multiple sclerosis (RRMS) and persistent disease activity confirmed by magnetic resonance imaging (MRI) despite immunosuppressive disease-modifying therapy (DMT). Methods: In this observational nationwide retrospective multicenter study, we first identified 351 off-label rituximab-treated patients through a cohort of 15,984 RRMS patients. In this group, we identified patients with disease activity prior to rituximab confirmed by MRI (one or more new T2 lesion and/or gadolinium-enhancing lesion) despite immunosuppressive DMT (fingolimod, natalizumab, or mitoxantrone) with a follow-up after rituximab initiation longer than 6 months. Outcome data were collected from the French Observatory of Multiple Sclerosis (OFSEP) register and medical charts. Results: A total of 50 patients were identified. Median rituximab treatment duration was 1.1 (0.5–6.4) year. Mean annualized relapse rate significantly decreased from 0.8 during last immunosuppressive DMT to 0.18 after rituximab ( p < 0.0001). While 72% of patients showed gadolinium-enhancing lesions on the last MRI performed during last immunosuppressive DMT, 8% of them showed gadolinium-enhancing lesions on the first MRI performed 6.1 (range 1.4–18.4) months after rituximab ( p < 0.0001). Conclusion: This study provides level IV evidence that rituximab reduces clinical and MRI disease activity in patients with active RRMS despite immunosuppressive DMT.

Early evidence of disease activity during fingolimod predicts medium-term inefficacy in relapsing-remitting multiple sclerosis

2020 ◽  
pp. 135245852096169
Author(s):  
Laura Ferrè ◽  
Andrea Mogavero ◽  
Ferdinando Clarelli ◽  
Lucia Moiola ◽  
Francesca Sangalli ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Cox Regression ◽  
First Year ◽  
Close Monitoring ◽  
Medium Term ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Background: Fingolimod (FTY) is an effective second-line drug for relapsing-remitting multiple sclerosis, with ~50% patients showing no evidence of disease activity (NEDA) after 2 years. Nonetheless, the early identification of non-responders is extremely important, to promptly address them to more aggressive drugs. Objectives: This cohort study evaluates FTY medium-term effectiveness, searching for early markers of treatment failure. Patients and methods: Three hundred eighty patients starting FTY were enrolled and classified according to NEDA and time to first relapse criteria at 4-year follow-up. Logistic and Cox regression analyses were applied to identify early predictors of non-response. Results: At 4 years, 65.6% of patients were free from relapses and 35.4% had NEDA. Female gender was associated with a higher risk of non-response. Moreover, evidence of clinical and/or magnetic resonance imaging (MRI) activity during the first year of treatment was highly predictive of disease activity in the follow-up: the positive predictive value for non-response was 0.74 for the presence of ⩾1 relapse, 0.73 for the presence of ⩾1 active MRI lesion, and 0.83 for the presence of both clinical and MRI activity. Conclusions: FTY effectiveness persists at medium-term follow-up; a close monitoring during the first year of treatment is warranted to early identify non-responders requiring treatment optimization.

scholarly journals Efficacy of Cladribine Tablets in high disease activity subgroups of patients with relapsing multiple sclerosis: A post hoc analysis of the CLARITY study

2018 ◽  
Vol 25 (6) ◽  
pp. 819-827 ◽  
Author(s):  
Gavin Giovannoni ◽  
Per Soelberg Sorensen ◽  
Stuart Cook ◽  
Kottil W Rammohan ◽  
Peter Rieckmann ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
High Disease Activity ◽  
Study Entry ◽  
T2 Lesions ◽  
Relapsing Remitting ◽  
Study Population ◽  
Magnetic Resonance Imaging Mri ◽  
Post Hoc ◽  
Relapsing Remitting Multiple Sclerosis

Background: In the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study, Cladribine Tablets significantly improved clinical and magnetic resonance imaging (MRI) outcomes (vs placebo) in patients with relapsing-remitting multiple sclerosis. Objective: Describe two clinically relevant definitions for patients with high disease activity (HDA) at baseline of the CLARITY study (utility verified in patients receiving placebo) and assess the treatment effects of Cladribine Tablets 3.5 mg/kg compared with the overall study population. Methods: Outcomes of patients randomised to Cladribine Tablets 3.5 mg/kg or placebo were analysed for subgroups using HDA definitions based on high relapse activity (HRA; patients with ⩾2 relapses during the year prior to study entry, whether on DMD treatment or not) or HRA plus disease activity on treatment (HRA + DAT; patients with ⩾2 relapses during the year prior to study entry, whether on DMD treatment or not, PLUS patients with ⩾1 relapse during the year prior to study entry while on therapy with other DMDs and ⩾1 T1 Gd+ or ⩾9 T2 lesions). Results: In the overall population, Cladribine Tablets 3.5 mg/kg reduced the risk of 6-month-confirmed Expanded Disability Status Scale (EDSS) worsening by 47% vs placebo. A risk reduction of 82% vs placebo was seen in both the HRA and HRA + DAT subgroups (vs 19% for non-HRA and 18% for non-HRA + DAT), indicating greater responsiveness to Cladribine Tablets 3.5 mg/kg in patients with HDA. There were consistent results for other efficacy endpoints. The safety profile in HDA patients was consistent with the overall CLARITY population. Conclusion: Patients with HDA showed clinical and MRI responses to Cladribine Tablets 3.5 mg/kg that were generally better than, or at least comparable with, the outcomes seen in the overall CLARITY population.

Effect of lateral therapy switches to oral moderate-efficacy drugs in multiple sclerosis: a nationwide cohort study

2021 ◽  
pp. jnnp-2020-324869 ◽  
Author(s):  
Mathias Due Buron ◽  
Tomas Kalincik ◽  
Finn Sellebjerg ◽  
Per Soelberg Sørensen ◽  
Melinda Magyari
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Absolute Risk ◽  
Dimethyl Fumarate ◽  
Interferon Β ◽  
First Line ◽  
Disease Modifying Therapies ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis

BackgroundSwitching between first-line disease-modifying therapies in patients with clinically stable relapsing–remitting multiple sclerosis (RRMS) due to reasons other than disease activity is frequent, but evidence on the effect of this practice is limited. We investigated the effect of switching patients with stable RRMS on occurrences of disability accumulation, relapses and future treatment discontinuation.MethodsUsing the Danish Multiple Sclerosis Registry, we identified patients with RRMS without disease activity who either (1) stayed on injectable platform therapy (interferon-β or glatiramer acetate) or (2) switched to dimethyl fumarate (DMF) or teriflunomide (TFL) and compared treatment outcomes using propensity-score-based methods and marginal structural models (MSM).ResultsWe included 3206 patients in the study. We found no change in risk of 6-month confirmed Expanded Disability Status Scale score worsening in patients switching to DMF (HR: 1.15, 95% CI 0.88 to 1.50) or TFL (HR: 1.16, 95% CI 0.92 to 1.46). The risk of suffering any relapse tended to decrease when switching to DMF (HR: 0.73, 95% CI 0.51 to 1.04) and tended to increase when switching to TFL (HR: 1.25, 95% CI 0.96 to 1.63). Absolute risk differences were small. MSM analyses showed similar results but did not find an increased relapse risk in TFL switchers.ConclusionSwitching from injectable platform therapies to oral first-line therapies in patients with clinically stable RRMS does not increase the risk of disability accumulation. While the postswitch risk of relapses trended towards marginally higher on TFL, this trend was eliminated by adjustment for time-variant confounders.

085 Clinical outcomes were better for relapsing-remitting multiple sclerosis (RRMS) patients who remained on natalizumab compared to those who switched to oral or injectable therapies after 2 years in the tysabri® observational program (TOP)

2018 ◽  
Vol 89 (6) ◽  
pp. A34.2-A34
Author(s):  
Helmut Butzkueven ◽  
Ludwig Kappos ◽  
Tim Spelman ◽  
Maria Trojano ◽  
Heinz Wiendl ◽  
...  
Keyword(s):  
Disease Activity ◽  
Clinical Outcomes ◽  
Cox Models ◽  
Relapse Risk ◽  
Lower Baseline ◽  
Relapsing Remitting ◽  
Study Support ◽  
Using Data ◽  
Relapsing Remitting Multiple Sclerosis

IntroductionNatalizumab is a high-efficacy RRMS therapy. Data on post-natalizumab disease activity may be important for physician consideration. We compared outcomes in patients who switched to an oral or injectable therapy or remained on natalizumab and analysed post-natalizumab relapse predictors using data from TOP, an ongoing 10 year observational study of natalizumab-treated RRMS patients.MethodsData from November 2016 were analysed for patients who stayed on natalizumab (≥3 years natalizumab and only natalizumab during follow-up; n=2466; mean time on natalizumab: 5.5 years) or switched to oral (n=660) or injectable (n=95) therapies for ≥1 year after ≥2 years on natalizumab (mean post-natalizumab follow-up 2.5 vs 2.4 years). Annualised relapse rates (ARRs) and Expanded Disability Status Scale (EDSS) worsening risks were evaluated. Disease activity predictors were compared using adjusted Cox models.ResultsRelapse risk was higher for oral switchers (hazard ratio [HR]=2.18; p<0.001) or injectable switchers (HR=3.02; p<0.001) than for patients who stayed on natalizumab >2 years. EDSS worsening risk was similar for oral (HR=1.19; p=0.266) and higher for injectable (HR=2.52; p<0.001) switchers compared with stayed-on-natalizumab patients. ARRs decreased after 2 years by 20.2% for stayed-on-natalizumab patients but increased from on-natalizumab rates by 17.8% in oral switchers (p<0.001) and 108.1% in injectable switchers (p<0.001). In oral switchers, lower relapse risk was predicted by shorter washout time (>12 weeks vs ≤4 weeks; HR=2.03; p<0.001), fewer pre-natalizumab relapses (HR=1.24/relapse in the prior year; p<0.001), lower baseline EDSS (>3.5 vs≤3.5; HR=1.44; p=0.007), and longer natalizumab duration (>3 years vs ≤3 years; HR=0.76; p=0.040).ConclusionStaying on natalizumab >2 years yields better clinical outcomes than switching to oral or injectable therapies. For those discontinuing natalizumab, switching to an oral versus an injectable yields better outcomes. Disease activity risk in oral switchers is predicted by washout time, pre-natalizumab relapses and EDSS, and time on natalizumab.Study supportBiogen.

scholarly journals Disease-modifying therapies modulate retinal atrophy in multiple sclerosis

Neurology ◽  
2017 ◽  
Vol 88 (6) ◽  
pp. 525-532 ◽  
Author(s):  
Julia Button ◽  
Omar Al-Louzi ◽  
Andrew Lang ◽  
Pavan Bhargava ◽  
Scott D. Newsome ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
First Year ◽  
Time Interval ◽  
Inclusion Criteria ◽  
Disease Modifying Therapies ◽  
Relapsing Remitting ◽  
Retinal Atrophy ◽  
Disease Modifying ◽  
Relapsing Remitting Multiple Sclerosis

Objective:To retrospectively investigate whether disease-modifying therapies (DMTs) exert differential effects on rates of retinal atrophy in relapsing-remitting multiple sclerosis (RRMS), as assessed using optical coherence tomography (OCT).Methods:A total of 402 patients with RRMS followed at the Johns Hopkins MS Center who underwent Cirrus-HD OCT were assessed for eligibility. Inclusion criteria included at least 1 year of OCT follow-up and adherence to a single DMT during the period of follow-up. Combined thickness of the ganglion cell + inner plexiform (GCIP) and other retinal layers was computed utilizing automated macular segmentation. Retinal thickness changes were analyzed using mixed-effects linear regression.Results:The effects of glatiramer acetate (GA; n = 48), natalizumab (NAT; n = 46), and interferon-β-1a subcutaneously (IFNSC; n = 35) and intramuscularly (IFNIM; n = 28) were assessed. Baseline analyses revealed no significant differences between groups in terms of age, sex, optic neuritis history, or follow-up duration. During follow-up, relative to NAT-treated patients, IFNSC- and GA-treated patients exhibited 0.37 μm/y (p < 0.001) and 0.14 μm/y (p = 0.035) faster rates of GCIP thinning, respectively, adjusting for the interval between initiation of DMT and OCT monitoring (gap time), age, sex, relapses, and disease duration. In the IFNSC group, GCIP thinning was 1.53 μm/y faster during the first year of therapy vs during the time interval afterwards (p < 0.001).Conclusions:Rates of GCIP atrophy in patients with RRMS vary according to DMT utilization. Our findings support OCT for monitoring neurodegenerative treatment effects in the retina, an easily accessible tissue, and as a practical outcome measure in RRMS clinical trials.

Increased cerebrospinal fluid albumin and immunoglobulin A fractions forecast cortical atrophy and longitudinal functional deterioration in relapsing-remitting multiple sclerosis

2017 ◽  
Vol 25 (3) ◽  
pp. 338-343 ◽  
Author(s):  
Julia Kroth ◽  
Dumitru Ciolac ◽  
Vinzenz Fleischer ◽  
Nabin Koirala ◽  
Julia Krämer ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Functional Disability ◽  
Immunoglobulin A ◽  
Cortical Atrophy ◽  
Disease Evolution ◽  
Relapsing Remitting ◽  
Magnetic Resonance Imaging Mri ◽  
Relapsing Remitting Multiple Sclerosis

Background: Currently, no unequivocal predictors of disease evolution exist in patients with multiple sclerosis (MS). Cortical atrophy measurements are, however, closely associated with cumulative disability. Objective: Here, we aim to forecast longitudinal magnetic resonance imaging (MRI)-driven cortical atrophy and clinical disability from cerebrospinal fluid (CSF) markers. Methods: We analyzed CSF fractions of albumin and immunoglobulins (Ig) A, G, and M and their CSF to serum quotients. Results: Widespread atrophy was highly associated with increased baseline CSF concentrations and quotients of albumin and IgA. Patients with increased CSFIgA and CSFIgM showed higher functional disability at follow-up. Conclusion: CSF markers of blood–brain barrier integrity and specific immune response forecast emerging gray matter pathology and disease progression in MS.

Personalized extended interval dosing of natalizumab in MS

Neurology ◽  
2020 ◽  
Vol 95 (6) ◽  
pp. e745-e754
Author(s):  
Zoé L.E. van Kempen ◽  
Erwin L.J. Hoogervorst ◽  
Mike P. Wattjes ◽  
Nynke F. Kalkers ◽  
Jop P. Mostert ◽  
...  
Keyword(s):  
Disease Activity ◽  
Extension Phase ◽  
T2 Lesions ◽  
Relapsing Remitting ◽  
Natalizumab Treatment ◽  
Mri Scans ◽  
Secondary Endpoints ◽  
Trough Concentrations ◽  
Relapsing Remitting Multiple Sclerosis

ObjectiveTo determine whether natalizumab efficacy is maintained when switching to personalized extended interval dosing based on individual natalizumab trough concentrations in patients with relapsing-remitting multiple sclerosis (RRMS).MethodsThis was a prospective multicenter single-arm trial with 1 year follow-up and a 1-year extension phase. Participants were adult persons with RRMS treated with natalizumab without disease activity in the year prior to enrollment. The natalizumab treatment interval was based on longitudinal natalizumab trough concentrations. Patients received 3 monthly MRI scans, relapse assessments, and disability scoring during follow-up. The primary endpoint was the occurrence of gadolinium-enhancing lesions on MRI. Secondary endpoints were new/enlarging T2 lesions on MRI and relapses and progression on the Expanded Disability Status Scale (EDSS) during follow-up and extension phase.ResultsSixty-one patients were included. Eighty-four percent extended the interval from a 4-week interval to a 5- to 7-week interval. No patient developed gadolinium-enhancing lesions (95% confidence interval [CI] 0%–7.4%) during follow-up. No new/enlarging T2 lesions (95% CI 0%–7.4%) or relapses (95% CI 0%–7.4%) were reported during follow-up and in the extension phase. Median EDSS was comparable at baseline (3.0, interquartile range [IQR] 2.0–5.0) and after follow-up (3.0, IQR 2.0–5.0).ConclusionPersonalized extended interval dosing did not induce recurrence of MS disease activity. Natalizumab efficacy was maintained in stable patients with RRMS receiving personalized extended interval dosing based on individual natalizumab concentrations.Classification of evidenceThis study provides Class IV evidence that personalized extended interval dosing of natalizumab does not result in recurrence of disease activity in stable patients with RRMS.

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