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.

scholarly journals Retrospective unbiased plasma lipidomic of progressive multiple sclerosis patients-identifies lipids discriminating those with faster clinical deterioration

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Mario Amatruda ◽  
Maria Petracca ◽  
Maureen Wentling ◽  
Benjamin Inbar ◽  
Kamilah Castro ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Progression ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Disease Course ◽  
Primary Progressive ◽  
T2 Lesions ◽  
Relapsing Remitting ◽  
One Year ◽  
Multiple Sclerosis Patients

Abstract The disease course of patients with a confirmed diagnosis of primary progressive multiple sclerosis (PPMS) is uncertain. In an attempt to identify potential signaling pathways involved in the evolution of the disease, we conducted an exploratory unbiased lipidomic analysis of plasma from non-diseased controls (n = 8) and patients with primary progressive MS (PPMS, n = 19) and either a rapid (PPMS-P, n = 9) or slow (PPMS-NP, n = 10) disease course based on worsening disability and/or MRI-visible appearance of new T2 lesions over a one-year-assessment. Partial least squares-discriminant analysis of the MS/MSALL lipidomic dataset, identified lipids driving the clustering of the groups. Among these lipids, sphingomyelin-d18:1/14:0 and mono-hexosylceramide-d18:1/20:0 were differentially abundant in the plasma of PPMS patients compared to controls and their levels correlated with MRI signs of disease progression. Lyso-phosphatidic acid-18:2 (LPA-18:2) was the only lipid with significantly lower abundance in PPMS patients with a rapidly deteriorating disease course, and its levels inversely correlated with the severity of the neurological deficit. Decreased levels of LPA-18:2 were detected in patients with more rapid disease progression, regardless of therapy and these findings were validated in an independent cohort of secondary progressive (SPMS) patients, but not in a third cohorts of relapsing–remitting (RRMS) patients. Collectively, our analysis suggests that sphingomyelin-d18:1/14:0, mono-hexosylceramide-d18:1/20:0, and LPA-18:2 may represent important targets for future studies aimed at understanding disease progression in MS.

Polymorphisms of innate pattern recognition receptors, response to interferon-beta and development of neutralizing antibodies in multiple sclerosis patients

2010 ◽  
Vol 16 (8) ◽  
pp. 942-949 ◽  
Author(s):  
Christian Enevold ◽  
Annette B Oturai ◽  
Per Soelberg Sørensen ◽  
Lars P Ryder ◽  
Nils Koch-Henriksen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Pattern Recognition ◽  
Neutralizing Antibodies ◽  
Interferon Beta ◽  
Pattern Recognition Receptors ◽  
Single Nucleotide ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

Background: Interferon-beta therapy of patients with relapsing—remitting multiple sclerosis involves repeated ‘immunizations’ with exogenous protein solutions. Innate pattern recognition receptors play an important role in immune responses towards foreign substances and may thus be related to treatment outcome. Objective: To determine the genotypes at 42 single nucleotide polymorphism loci in selected pattern recognition receptors for 567 prospectively followed relapsing—remitting multiple sclerosis patients treated with recombinant interferon-beta, and test for relationships to several outcome parameters, including formation of interferon-beta neutralizing antibodies. Results: The results suggest an association between the rs5743810 polymorphism (Ser249Pro) of TLR6 and development of neutralizing antibodies after 24 months of therapy in males ( p = 0.00002), but not in females ( p = 0.2). This association survived crude Bonferroni correction ( pcorrected = 0.02). Additional associations were observed in carriers of the TLR2-rs5743708 and NOD2-rs3135499 SNPs (time to relapse), the TLR7-rs179008 and NOD1-rs2075820 SNPs (time to disease progression) and the TLR4-rs7873784, TLR9-rs5743836, and NOD2-rs2066842 SNPs (frequency of neutralizing antibodies development). All of these, however, failed to survive correction for multiple testing. There were no significant differences between interferon-beta responders and non-responders for any of the investigated single nucleotide polymorphisms. Conclusions: The rs5743810 polymorphism of TLR6 may be involved in development of anti-interferon-beta antibodies in males, although further studies are required to firmly establish this.

scholarly journals Assessment of treatment patterns associated with injectable disease-modifying therapy among relapsing–remitting multiple sclerosis patients

2017 ◽  
Vol 3 (1) ◽  
pp. 205521731769611 ◽  
Author(s):  
J Nicholas ◽  
JJ Ko ◽  
Y Park ◽  
P Navaratnam ◽  
HS Friedman ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Medical Records ◽  
Treatment Patterns ◽  
Oral Disease ◽  
Disease Modifying Therapy ◽  
Relapsing Remitting ◽  
Disease Modifying ◽  
Remitting Multiple Sclerosis ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

Background Availability of oral disease-modifying therapy (DMT) for relapsing–remitting multiple sclerosis (RRMS) may affect injectable DMT (iDMT) treatment patterns. Objective The objective of this paper is to evaluate iDMT persistency, reasons for persistency lapses, and outcomes among newly diagnosed RRMS patients. Methods Medical records of 300 RRMS patients initiated on iDMT between 2008 and 2013 were abstracted from 18 US-based neurology clinics. Eligible patients had ≥3 visits: pre-iDMT initiation, iDMT initiation (index), and ≥1 visit within 24 months post-index. MS-related symptoms, relapses, iDMT treatment patterns (i.e. persistency, discontinuation, switching, and restart), and reasons for non-persistency were tracked for 24 months. Results At 24 months, iDMT persistency was 61.0%; 28.0% of patients switched to another DMT, 8.0% discontinued, and 3.0% stopped and restarted the same iDMT. The most commonly identified reasons for non-persistency were perceived lack of efficacy (22.2%), adverse events (18.8%), and fear of needles/self-injecting (9.4%). At 24 months, 38.0% of patients had experienced a relapse and 11.0% had changes in MRI lesion counts. Patients without MS-related symptoms at index reported increases in the incidence of these symptoms at 24 months. Conclusions Non-persistency with iDMT remains an issue in the oral DMT age. Many patients still experienced relapses and disease progression, and should consider switching to more effective therapies.

scholarly journals Assessment of Serum Nitrogen Species and Inflammatory Parameters in Relapsing-Remitting Multiple Sclerosis Patients Treated with Different Therapeutic Approaches

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Natalia Niedziela ◽  
Monika Adamczyk-Sowa ◽  
Jacek T. Niedziela ◽  
Bogdan Mazur ◽  
Ewa Kluczewska ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Second Line ◽  
Nitrogen Species ◽  
First Line ◽  
Inflammatory Parameters ◽  
Disease Modifying Therapy ◽  
Relapsing Remitting ◽  
Disease Modifying ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

The role of nitric oxide and its reactive derivatives (NOx) is well known in the pathogenesis of multiple sclerosis, which is an inflammatory disease whileNOxseems to be important in coordinating inflammatory response. The purpose of the present study was to assess serumNOxas one of the nitrogen species and inflammatory parameters in relapsing-remitting multiple sclerosis patients and to compare the effectiveness of various types of disease-modifying therapies that reduce nitric oxide and inflammatory biomarkers. ElevatedNOxlevel was observed in patients who received the first-line disease-modifying therapy (interferons beta-1a and beta-1b) in comparison with the subjects treated with the second-line disease-modifying therapy (natalizumab; fingolimod) and healthy controls without significant differences in C-reactive protein and interleukin-1 beta. A negative correlation was observed between serumNOxlevel and the duration of multiple sclerosis confirmed in the whole study population and in subjects treated with the first-line agents. Only serumNOx, concentration could reveal a potential efficacy of disease-modifying therapy with a better reduction inNOxlevel due to the second-line agents of disease-modifying therapy.

scholarly journals GP.02 A population-based study of “no evident disease activity” (NEDA) in multiple sclerosis

2018 ◽  
Vol 45 (s2) ◽  
pp. S8-S8
Author(s):  
NE Parks ◽  
SJ Pittock ◽  
J Mandrekar ◽  
OH Kantarci ◽  
CF Lucchinetti ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Retrospective Chart Review ◽  
Population Based ◽  
Disease Modifying Therapy ◽  
Disability Status ◽  
Relapsing Remitting ◽  
One Year ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Incident Cases ◽  
Referral Bias

Background: NEDA is a composite measure that may ultimately influence clinical decisions concerning switches of disease modifying therapy (DMT) for relapsing remitting multiple sclerosis (RRMS) patients. Cohort studies from MS clinics suggest NEDA is not sustained over time in most patients despite DMT but may be limited by referral bias. We investigated NEDA in a population-based RRMS cohort. Methods: We identified all incident cases of RRMS in Olmsted County from 01/01/2000-12/31/2011. Retrospective chart review was conducted to determine persistence of NEDA -following RRMS diagnosis. NEDA failure was defined as new MRI activity, relapse, or expanded disability status scale (EDSS) -worsening. Results: There were 93 incident cases of RRMS with 82 individuals having sufficient follow-up to determine persistence of NEDA. Prior to NEDA failure 44 were not on DMT, 37 were on first-tier, injectable DMT, and 1 received mitoxantrone. NEDA was maintained by 63% at 1 year, 38% at 2 years, 19% at 5 years, and 12% at 10 years. Disability measured by EDSS was no different at 10 years in patients maintaining NEDA versus those that failed NEDA at one year (p=0.3). Conclusions: Maintenance of NEDA beyond 2 years is infrequent among a population-based cohort of newly diagnosed RRMS patients and similar to prior clinic-based cohorts.

scholarly journals Safety and Efficacy of Fingolimod in Treatment-Naïve Multiple Sclerosis Patients

2011 ◽  
Vol 3 ◽  
pp. JCNSD.S5120 ◽  
Author(s):  
James J. Marriott
Keyword(s):  
Multiple Sclerosis ◽  
The United States ◽  
Phase Iii ◽  
Disease Modifying Therapy ◽  
Relapsing Remitting ◽  
Treatment Naïve ◽  
Disease Modifying ◽  
Remitting Multiple Sclerosis ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

Fingolimod was recently approved for use in the United States after two phase III trials confirmed its effectiveness in reducing disease activity in relapsing-remitting multiple sclerosis. These positive results, coupled with the important fact that this is the first oral disease-modifying therapy, has lead to considerable enthusiasm amongst physicians and patients. However, fingolimod is associated with rare but serious adverse events. In addition, unlike conventional disease-modifying therapies, cardiopulmonary, ophthalmological and dermatological safety monitoring unfamiliar to both neurologists and patients is required before and during treatment. This paper will discuss these issues from the perspective of using fingolimod as a first-line disease-modifying therapy in treatment-Naïve relapsing-remitting multiple sclerosis patients

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