scholarly journals Four-year safety and effectiveness data from patients with multiple sclerosis treated with fingolimod: The Spanish GILENYA registry

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258437
Author(s):  
J. E. Meca-Lallana ◽  
C. Oreja-Guevara ◽  
D. Muñoz ◽  
J. Olascoaga ◽  
A. Pato ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Patient Profile ◽  
T2 Lesions ◽  
Disease Modifying Therapy ◽  
Relapsing Remitting ◽  
Previously Treated ◽  
Risk Balance ◽  
The Mean ◽  
Effectiveness Data

Objective To describe the profile of patients with multiple sclerosis (MS) treated with fingolimod in Spain and to assess the effectiveness and safety of fingolimod after 4 years of inclusion in the Spanish Gilenya Registry. Methods An observational, retrospective/prospective, multicenter case registry, including all patients with relapsing-remitting MS (RRMS) starting treatment with fingolimod in 43 centers in Spain. Analyses were performed in the overall population and in subgroups according to prior disease-modifying therapy (DMT): glatiramer acetate/interferon beta-1 (BRACE), natalizumab, other treatment, or naïve. Results Six hundred and sixty-six evaluable patients were included (91.1% previously treated with at least one DMT). The mean annualized relapse rate (ARR) prior to fingolimod was 1.12, and the mean EDSS at fingolimod initiation was 3.03. Fingolimod reduced the ARR by 71.4%, 75%, 75.5%, and 80.3%, after 1, 2, 3 and 4 years, respectively (p<0.001). This significant reduction in the ARR continued to be observed in all subgroups. After 4 years, the EDSS showed a minimal deterioration, with the EDSS scores from year 1 to year 4 remaining mostly stable. The percentage of patients without T1 Gd+ lesions progressively increased from 45.6% during the year prior to fingolimod initiation to 88.2% at year 4. The proportion of patients free from new/enlarged T2 lesions after 4 years of fingolimod treatment was 80.3%. This trend in both radiological measures was also observed in the subgroups. Adverse events (AEs) were experienced by up to 41.6% of patients (most commonly: lymphopenia [12.5%] and urinary tract infection [3.7%]). Most AEs were mild in severity, 3.6% of patients had serious AEs. Conclusions The patient profile was similar to other observational studies. The results obtained from the long-term use of fingolimod showed that it was effective, regardless of prior DMT, and it had adequate safety results, with a positive benefit-risk balance.

Minimal evidence of disease activity (MEDA) in relapsing-remitting multiple sclerosis

2020 ◽  
Vol 91 (3) ◽  
pp. 271-277 ◽  
Author(s):  
Luca Prosperini ◽  
Chiara Mancinelli ◽  
Shalom Haggiag ◽  
Cinzia Cordioli ◽  
Laura De Giglio ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
T2 Lesions ◽  
Relapsing Remitting ◽  
Second Year ◽  
Remitting Multiple Sclerosis ◽  
A Minor ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Minimal Evidence

ObjectiveThis study aimed to define the minimal evidence of disease activity (MEDA) during treatment that can be tolerated without exposing patients with relapsing-remitting multiple sclerosis at risk of long-term disability.MethodsWe retrospectively collected data of patients followed up to 10 years after starting interferon beta or glatiramer acetate. Survival analyses explored the association between the long-term risk of reaching an Expanded Disability Status Scale≥6.0 and early clinical and MRI activity assessed after the first and second year of treatment. Early disease activity was classified by the so-called ‘MAGNIMS score’ (low: no relapses and <3 new T2 lesions; medium: no relapses and ≥3 new T2 lesions or 1 relapse and 0–2 new T2 lesions; high: 1 relapse and ≥3 new T2 lesions or ≥2 relapses) and the absence or presence of contrast-enhancing lesions (CELs).ResultsAt follow-up, 148/1036 (14.3%) patients reached the outcome: 61/685 (8.9%) with low score (reference category), 57/241 (23.7%) with medium score (HR=1.94, p=0.002) and 30/110 (27.3%) with high score (HR=2.47, p<0.001) after the first year of treatment. In the low score subgroup, the risk was further reduced in the absence (49/607, 8.1%) than in the presence of CELs (12/78, 15.4%; HR=2.11, p=0.01). No evident disease activity and low score in the absence of CELs shared the same risk (p=0.54). Similar findings were obtained even after the second year of treatment.ConclusionsEarly marginal MRI activity of one to two new T2 lesions, in the absence of both relapses and CELs, is associated with a minor risk of future disability, thus representing a simple and valuable definition for MEDA.

scholarly journals Ocrelizumab treatment for relapsing-remitting multiple sclerosis after a suboptimal response to previous disease-modifying therapy: A nonrandomized controlled trial

2021 ◽  
pp. 135245852110357
Author(s):  
Bianca Weinstock-Guttman ◽  
Robert Bermel ◽  
Gary Cutter ◽  
Mark S Freedman ◽  
Thomas P Leist ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Controlled Trial ◽  
Intention To Treat ◽  
T2 Lesions ◽  
Disease Modifying Therapy ◽  
Relapsing Remitting ◽  
Activity Measures ◽  
Disease Modifying ◽  
Magnetic Resonance Imaging Mri

Background: Many patients with multiple sclerosis (MS) experience suboptimal disease control despite the use of disease-modifying therapy (DMT). Objective: To assess the efficacy and safety of ocrelizumab (OCR) in patients with relapsing-remitting MS (RRMS) and suboptimal response to prior DMTs. Methods: Patients with RRMS and suboptimal responses (one clinically reported relapse and/or lesion activity) after ⩾ 6 months on another DMT were enrolled. OCR 600 mg was given intravenously every 24 weeks. The primary outcome was no evidence of disease activity (NEDA), defined as the absence of protocol-defined relapse, confirmed disability progression (CDP), T1 Gd-enhancing lesions, and new/enlarging T2 lesions. Results: The intention-to-treat (ITT) population included 608 patients; NEDA was analyzed in a modified ITT (mITT) population ( n = 576 (94.7%)). Over 96 weeks, 48.1% of mITT patients achieved NEDA, and most were free from protocol-defined relapse (89.6%), CDP (89.6%), and T1 Gd-enhancing lesions (95.5%); 59.5% had no new/enlarging T2 lesions. Safety observations were consistent with findings in the pivotal trials. Conclusion: Consistent efficacy of OCR on clinical and magnetic resonance imaging (MRI) disease activity measures and progression was shown in patients with RRMS and a suboptimal response to prior DMTs; no new safety signals were observed.

scholarly journals Temporal profile of serum neurofilament light in multiple sclerosis: Implications for patient monitoring

2020 ◽  
pp. 135245852097257
Author(s):  
Peter A Calabresi ◽  
Douglas L Arnold ◽  
Dipen Sangurdekar ◽  
Carol M Singh ◽  
Arman Altincatal ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
T2 Lesions ◽  
Disease Modifying Therapy ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Magnetic Resonance Imaging Mri ◽  
Post Hoc

Objective: To understand how longitudinal serum neurofilament light chain (sNfL) patterns can inform its use as a prognostic biomarker in multiple sclerosis (MS) and evaluate whether sNfL reflects MS disease activity and disease-modifying therapy usage. Methods: This was a post hoc analysis of longitudinal data and samples from the ADVANCE trial (NCT00906399) of patients with relapsing–remitting MS (RRMS). sNfL was measured every 3 months for 2 years, then every 6 months for 4 years. Regression models explored how sNfL data predicted 4-year values of brain volume, expanded disability status scale score, and T2 lesions. sNfL levels were assessed in those receiving placebo, peginterferon beta-1a, and those with disease activity. Results: Baseline sNfL was a predictor of 4-year brain atrophy and development of new T2 lesions. Clinical ( p = 0.02) and magnetic resonance imaging (MRI) ( p < 0.01) outcomes improved in those receiving peginterferon beta-1a whose sNfL decreased to <16 pg/mL after 12 months versus those whose sNfL remained ⩾16 pg/mL. Mean sNfL levels decreased in peginterferon beta-1a-treated patients and increased in placebo-treated patients (–9.5% vs. 6.8%; p < 0.01). sNfL was higher and more variable in patients with evidence of active MS. Conclusion: These data support sNfL as a prognostic and disease-monitoring biomarker for RRMS.

scholarly journals Effects of Adjunct Low-Dose Vitamin D on Relapsing-Remitting Multiple Sclerosis Progression: Preliminary Findings of a Randomized Placebo-Controlled Trial

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Vahid Shaygannejad ◽  
Mohsen Janghorbani ◽  
Fereshteh Ashtari ◽  
Hamed Dehghan
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
Relapse Rate ◽  
Low Dose ◽  
Disease Modifying Therapy ◽  
Relapsing Remitting ◽  
The Mean ◽  
Disease Modifying ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

The aim of this preliminary study was to evaluate the effect of low-dose oral vitamin D in combination with current disease-modifying therapy on the prevention of progression of relapsing-remitting multiple sclerosis (RRMS). A phase II double-blind placebo-controlled randomized clinical trial conducted between October 2007 and October 2008 included 50 patients with confirmed RRMS aged 25 to 57 years and normal serum 25-hydroxyvitamin D. They were randomly allocated to receive 12 months of treatment with either escalating calcitriol doses up to 0.5 μg/day or placebo combined with disease-modifying therapy. Response to treatment was assessed at eight-week intervals. In both groups, the mean relapse rate decreased significantly (P<0.001). In the 25 patients treated with placebo, the mean (SD) Expanded Disability Status Scale (EDSS) increased from 1.70 (1.21) at baseline to 1.94 (1.41) at the end of study period (P<0.01). Average EDSS and relapse rate at the end of trial did not differ between groups. Adding low-dose vitamin D to routine disease-modifying therapy had no significant effect on the EDSS score or relapse rate. A larger phase III multicenter study of vitamin D in RRMS is warranted to more assess the efficacy of this intervention.

scholarly journals MS TREATMENT OPTIMIZATION: FACTORS ASSOCIATED WITH POOR CLINICAL RESPONSE IN NAB POSITIVE PATIENTS

2016 ◽  
Vol 15 (3) ◽  
pp. 119-126
Author(s):  
A. Cornea ◽  
◽  
R. Tudor ◽  
A. Petre ◽  
M. Simu ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Neutralizing Antibodies ◽  
Clinical Decision ◽  
Treatment Optimization ◽  
T2 Lesions ◽  
Disease Modifying Therapy ◽  
Relapsing Remitting ◽  
One Year ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

Background and purpose. Interferon beta (IFN beta) belongs to the first line of disease modifying therapy drugs in the treatment of relapsing-remitting multiple sclerosis being widely used in the chronic treatment of this pathology. The serum presence of the neutralizing antibodies (Nabs) has been shown to alter the treatment response, its routine applicability being still debated. In an observational study, we aimed to determine in the Nabs positive patients, correlations with other clinical factors which contribute to IFN beta decreased efficacy. Methods. We measured Nabs in 104 patients who were on IFN beta therapy (29.8% on IFN beta 1a s.c., 27.88% on IFN beta 1a i.m. and 42,3 on IFN beta 1b s.c.) for at least one year in our clinic. Serum was collected at 24 h after treatment injection to avoid transitory antibody peak (12-18 h post administration). We considered positive the patients with a titer higher than 20 TRU. Results. The prevalence of Nabs in our group of patients was 13.43% (42.85% IFN Beta 1b s.c., 50% IFN beta 1a s.c. and 7.14% IFN beta 1 a i.m.). Nabs positivity was associated with an increase in the relapse rate (for IFB beta 1a and 1b s.c. groups) and progression for IFN beta 1 b s.c. patient group. Conclusions. The routine clinical testing for Nabs should impact the clinical decision of switching therapy in multiple sclerosis patients that present with an increased number of relapses, EDSS progression or a higher number of MRI T2 lesions.

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