Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 53
Filter
1.
Mult Scler ; 28(10): 1576-1590, 2022 09.
Article in English | MEDLINE | ID: covidwho-1997275

ABSTRACT

BACKGROUND: Ofatumumab is approved for the treatment of relapsing multiple sclerosis (RMS). Ongoing safety reporting is crucial to understand its long-term benefit-risk profile. OBJECTIVE: Report the safety and tolerability of ofatumumab in RMS after extended treatment up to 3.5 years. METHODS: Patients completing ASCLEPIOS I/II (phase 3), APLIOS, or APOLITOS (phase 2) trials could enter ALITHIOS, a phase 3b, open-label, long-term safety study. We analyzed cumulative data of continuous ofatumumab treatment and of patients newly switched from teriflunomide. RESULTS: The safety population had 1969 patients: 1292 continuously treated with ofatumumab (median time-at-risk 35.5 months, 3253 patient-years) and 677 newly switched (median time-at-risk 18.3 months, 986 patient-years). A total of 1650 patients (83.8%) had ⩾1 adverse events and 191 (9.7%) had ⩾1 serious adverse events. No opportunistic infections or progressive multifocal leukoencephalopathy events were identified; the risk of malignancies was low. Mean serum immunoglobulin (Ig) G levels remained stable. Mean IgM levels decreased but remained above the lower limit of normal in most. Serious infection incidence was low; decreased Ig levels were not associated with serious infections. CONCLUSION: In patients with up to 3.5 years' exposure, ofatumumab was well tolerated, with no new safety risks identified. These findings, with its established effectiveness, support a favorable benefit-risk profile of ofatumumab in RMS.


Subject(s)
Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , Antibodies, Monoclonal, Humanized/adverse effects , Humans , Multiple Sclerosis/drug therapy , Multiple Sclerosis, Relapsing-Remitting/drug therapy
2.
Continuum (Minneap Minn) ; 28(4): 1025-1051, 2022 08 01.
Article in English | MEDLINE | ID: covidwho-1987099

ABSTRACT

PURPOSE OF REVIEW: Given the expansion of options for the treatment of relapsing multiple sclerosis, this review outlines the framework for developing a treatment strategy, with consideration of when to switch or discontinue therapies, and a comprehensive elaboration of the mechanisms of action, efficacy, and safety considerations for each of the therapeutic classes. RECENT FINDINGS: The armamentarium of immunotherapies has grown rapidly, to encompass 19 US Food and Drug Administration (FDA)-approved immunotherapies available in 2021, which are addressed in the review. The coronavirus pandemic that began in 2020 underscored existing concerns regarding vaccine efficacy in those treated with immune-suppressing immunotherapies, which are also addressed here. SUMMARY: By choosing a treatment strategy before exploring the individual medications, patients and providers can focus their efforts on a subset of the therapeutic options. Although the mechanisms of action, routes of administration, efficacy, safety, and tolerability of the described agents and classes differ, all are effective in reducing relapse frequency in multiple sclerosis (MS), with most also showing a reduction in the accumulation of neurologic disability. These powerful effects are improving the lives of people with MS. Pharmacovigilance is critical for the safe use of these immune-modulating and -suppressing agents, and vaccine efficacy may be reduced by those with immune-suppressing effects.


Subject(s)
Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , Humans , Immunosuppressive Agents , Immunotherapy , Multiple Sclerosis/drug therapy , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Recurrence , United States , United States Food and Drug Administration
3.
Mult Scler Relat Disord ; 63: 103863, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1931042

ABSTRACT

BACKGROUND: Multiple sclerosis (MS) patients receive immunomodulatory treatments which can influence their ability to maintain vaccine specific serological response overtime. MS patients treated with cladribine tablets developed a positive serology response following two doses of mRNA COVID-19 vaccine. However, there is only limited data regarding the effect of cladribine tablets on long-term humoral response after the second and the third booster. METHODS: Serology response to SARS-CoV-2 was tested in healthy controls (HCs) and MS patients treated with cladribine tablets 6 and 9-12 months after the second dose, and 1 and 3-6 months following the third booster-dose of the BTN162b2 mRNA vaccine. RESULTS: Thirty-five out of 36 MS patients treated with cladribine tablets and 100% (46/46) of HCs had a positive serology response up to 10 months after the second vaccine dose. In addition, all cladribine tablets -treated MS patients (22/22) and HCs (24/24) had a positive robust serology response following the third vaccine with a positive humoral response sustain up to 6 months. One month after the third vaccine dose IgG levels were significantly lower in patients treated with cladribine tablets compared to HCs (15,598+11,313 vs 26,394+11,335, p<0.01). Six-month post second vaccine and 3-6 months post third vaccine there was no difference in IgG levels between the groups (1088.0 ± 1072.0 vs 1153.0 ± 997.1, p = 0.79; 5234+4097 vs 11,198+14,679, p = 0.4). CONCLUSION AND RELEVANCE: MS patients treated with cladribine tablets have sustained positive vaccine specific serology response following the second and third SARS-CoV-2 vaccine dose.


Subject(s)
COVID-19 , Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Cladribine/adverse effects , Humans , Immunoglobulin G/therapeutic use , Immunosuppressive Agents/adverse effects , Multiple Sclerosis/drug therapy , Multiple Sclerosis, Relapsing-Remitting/drug therapy , SARS-CoV-2 , Tablets , Vaccines, Synthetic , mRNA Vaccines
4.
Syst Rev ; 11(1): 134, 2022 07 01.
Article in English | MEDLINE | ID: covidwho-1923579

ABSTRACT

BACKGROUND: Multiple sclerosis (MS) is an inflammatory and degenerative disease of the central nervous system with an increasing worldwide prevalence. Since 1993, more than 15 disease-modifying immunotherapies (DMTs) have been licenced and have shown moderate efficacy in clinical trials. Based on the heterogeneity of the disease and the partial effectiveness of therapies, a personalised medicine approach would be valuable taking individual prognosis and suitability of a chosen therapy into account to gain the best possible treatment effect. The primary objective of this review is to assess the differential treatment effects of all approved DMTs in subgroups of adults with clinically isolated syndrome or relapsing forms of MS. We will analyse possible treatment effect modifiers (TEM) defined by baseline demographic characteristics (gender, age), and diagnostic (i.e. MRI measures) and clinical (i.e. relapses, disability level) measures of MS disease activity. METHODS: We will include all published and accessible unpublished primary and secondary analyses of randomised controlled trials (RCTs) with a follow-up of at least 12 months investigating the efficacy of at least one approved DMT, with placebo or other approved DMTs as control intervention(s) in subgroups of trial participants. As the primary outcome, we will address disability as defined by the Expanded Disability Status Scale or multiple sclerosis functional composite scores followed by relapse frequency, quality of life measures, and side effects. MRI data will be analysed as secondary outcomes. MEDLINE, EMBASE, CINAHL, LILACS, CENTRAL and major trial registers will be searched for suitable studies. Titles and abstracts and full texts will be screened by two persons independently using Covidence. The risk of bias will be analysed based on the Cochrane "Risk of Bias 2" tool, and the certainty of evidence will be assessed using GRADE. Treatment effects will be reported as rate ratio or odds ratio. Primary analyses will follow the intention-to-treat principle. Meta-analyses will be carried out using random-effects models. DISCUSSION: Given that individual patient data from clinical studies are often not available, the review will allow to analyse the evidence on TEM in MS immunotherapy and thus support clinical decision making in individual cases. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021279665 .


Subject(s)
Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , Adult , Biomarkers , Demography , Humans , Immunologic Factors/therapeutic use , Immunotherapy , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Multiple Sclerosis, Relapsing-Remitting/therapy , Neoplasm Recurrence, Local , Randomized Controlled Trials as Topic , Review Literature as Topic , Systematic Reviews as Topic
5.
Mult Scler ; 28(7): 1126-1130, 2022 06.
Article in English | MEDLINE | ID: covidwho-1861989

ABSTRACT

BACKGROUND: Despite impressive efficacy in immunocompetent individuals, the immunogenicity of a single dose of COVID-19 vaccine in B-cell-deplete patients remains unknown. OBJECTIVES: We aimed to quantify real-world vaccine immunogenicity in ocrelizumab recipients. METHODS: We measured post-vaccination SARS-COV-2 immunoglobulin G (IgG) in ocrelizumab recipients using a highly sensitive Luminex assay. RESULTS: 44.1% of patients had detectable SARS-COV-2-IgG 21+ days after one vaccine dose, regardless of vaccine type (AZD1222 vs BNT162b2, odds ratio (OR) = 0.62, 95% confidence interval (CI) = 0.157-2.32, p = 0.72). B-cell count strongly predicted seroconversion (ß1 = 12.38, 95% CI = 4.59-20.16, p = 0.0029), but undetectable B-cells did not preclude it. The second vaccine seroconverted 53% of the patients who had not already responded to dose 1. CONCLUSION: Humoral response after one COVID-19 vaccine dose is lower than expected in CD20-deplete patients.


Subject(s)
COVID-19 , Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , Antibodies, Monoclonal, Humanized , Antibodies, Viral , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines , ChAdOx1 nCoV-19 , Humans , Immunoglobulin G/therapeutic use , Multiple Sclerosis/drug therapy , Multiple Sclerosis, Relapsing-Remitting/drug therapy , SARS-CoV-2 , Seroconversion
6.
Mult Scler ; 28(7): 1121-1125, 2022 06.
Article in English | MEDLINE | ID: covidwho-1861984

ABSTRACT

In this observational study, 159 patients with multiple sclerosis received personalized dosing of ocrelizumab incentivized by the COVID-19 pandemic. Re-dosing was scheduled when CD19 B-cell count was ⩾10 cells/µL (starting 24 weeks after the previous dose, repeated 4-weekly). Median interval until re-dosing or last B-cell count was 34 [30-38] weeks. No clinical relapses were reported and a minority of patients showed Expanded Disability Status Scale (EDSS) progression. Monthly serum neurofilament light levels remained stable during extended intervals. Two (1.9%) of 107 patients with a follow-up magnetic resonance imaging (MRI) scan showed radiological disease activity. Personalized dosing of ocrelizumab could significantly extend intervals with low short-term disease activity incidence, encouraging future research on long-term safety and efficacy.


Subject(s)
COVID-19 , Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , Antibodies, Monoclonal, Humanized , Humans , Multiple Sclerosis/drug therapy , Multiple Sclerosis/epidemiology , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Multiple Sclerosis, Relapsing-Remitting/epidemiology , Pandemics
7.
J Neurol Sci ; 438: 120292, 2022 07 15.
Article in English | MEDLINE | ID: covidwho-1851604

ABSTRACT

OBJECTIVES: The present study aims to describe the evolution of teriflunomide use for multiple sclerosis (MS) in the clinical setting, in particular for naïve patients and young women. Predictors of treatment response were also investigated. METHODS: This was an independent, retrospective, real-world monocentric study. We analysed the use of teriflunomide from 2016 to 2020 in patients categorized as naïve or switchers, and assessed the variations in its use in men and women by age group. Clinical and MRI data of treated patients were evaluated, and NEDA-3 status at 24 and 36 months was defined. Determinants of therapeutic response were examined using regression analysis. RESULTS: The study included 319 MS patients exposed to teriflunomide [209 women (65.5%)]. Of these, 67 (21%) were naïve and 252 (79%) were switchers. A 20% increase of teriflunomide use in the naïve group in the past two years, particularly in 2020, the first year of global Sars-Cov-2 spread, was observed. An increase of teriflunomide use of more than 10% in young women under age 45 was also reported. NEDA-3 status was calculated for 204 patients after 24 months and was achieved in 120 (58.8%) of these ones. NEDA-3 was also achieved in 92/160 (56.8%) patients at 36 months. A lower ARR in the two years prior to teriflunomide treatment (p = 0.026), lower baseline age (p = 0.05), and lower EDSS score (p = 0.009) were associated with achievement of the NEDA-3. CONCLUSIONS: Our study confirms a major evolution in teriflunomide use in clinical settings, particularly for naïve patients and young women.


Subject(s)
COVID-19 , Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , Crotonates , Female , Humans , Hydroxybutyrates , Male , Middle Aged , Multiple Sclerosis/drug therapy , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Nitriles , Retrospective Studies , SARS-CoV-2 , Toluidines
8.
Mult Scler Relat Disord ; 61: 103777, 2022 May.
Article in English | MEDLINE | ID: covidwho-1757691

ABSTRACT

BACKGROUND: Iran, as a middle income country, is one of the places with high and rising prevalence of multiple sclerosis (MS). Regarding the substantial economic burden, reviewing the trend in prescribed disease modifying treatments (DMTs) could be of help. Here we studied the DMT information of nearly 14000 MS cases and its trends change for 30 years to improve health services to patients. METHODS: The population base of this descriptive-analytical (cross-sectional) study consisted of all MS patients in the nationwide MS registry of Iran (NMSRI), up to August 1, 2021. Registrars from 15 provinces, 24 cities, 13 hospitals,8 MS associations, 16 private offices, and 7 clinics had entered the data. RESULTS: Overall, 14316 cases were enrolled. The majority (76.1%) were female. The youngest and eldest patients were 5 and 78 years old, respectively. Diagnosis delay was under one year in most cases (median: 0, IQR: 0 - 1). Most (61.4%) had RRMS. Generally, platform injectables (IFN beta, glatiramer acetate) were the most used DMTs until 2010. It seems that introduction of newer agents (antiCD20s and oral DMTs) resulted in a decrease in the use of former drugs since around 2015. Some unusual practices are prominent such as using not approved DMTs for PPMS over the years, or administering high efficacy drugs like natalizumab for CIS. The results indicate the remaining popularity of first line injectable DMTs in female and pediatric patients. DISCUSSION: Mean age (SD) at onset in our study (29 ± 8.8) is near the statistics in Asia and Oceania (28 ± 0.7). Concerns about COVID-19 had a noticeable impact on administering high efficacy drugs like rituximab and fingolimod. However, in male patients this approach has not been the case. It may be related to more aggressive disease course in this group. The other possible explanation could be planning for pregnancy in female cases. The popularity of platform injectable drugs in pediatric MS may be related to its favorable safety profile over the years. Another point in this group, is the superiority of rituximab over other highly efficient medications.


Subject(s)
COVID-19 , Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , Adolescent , Adult , Aged , Child , Child, Preschool , Cross-Sectional Studies , Female , Glatiramer Acetate/therapeutic use , Humans , Immunosuppressive Agents/therapeutic use , Iran/epidemiology , Male , Middle Aged , Multiple Sclerosis/drug therapy , Multiple Sclerosis/epidemiology , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Prescriptions , Rituximab/therapeutic use , Young Adult
10.
Neurol Neuroimmunol Neuroinflamm ; 9(2)2022 03.
Article in English | MEDLINE | ID: covidwho-1643219

ABSTRACT

BACKGROUND AND OBJECTIVES: Several studies have assessed risk factors associated with the severity of COVID-19 outcomes in people with multiple sclerosis (PwMS). The potential role of disease-modifying therapies (DMTs) and demographic and clinical factors on the risk of acquiring SARS-CoV-2 infection has not been evaluated so far. The objective of this study was to assess risk factors of contracting SARS-CoV-2 infection in PwMS by using data collected in the Italian MS Register (IMSR). METHODS: A case-control (1:2) study was set up. Cases included PwMS with a confirmed diagnosis of COVID-19, and controls included PwMS without a confirmed diagnosis of COVID-19. Both groups were propensity score-matched by the date of COVID-19 diagnosis, the date of last visit, and the region of residence. No healthy controls were included in this study. COVID-19 risk was estimated by multivariable logistic regression models including demographic and clinical covariates. The impact of DMTs was assessed in 3 independent logistic regression models including one of the following covariates: last administered DMT, previous DMT sequences, or the place where the last treatment was administered. RESULTS: A total of 779 PwMS with confirmed COVID-19 (cases) were matched to 1,558 PwMS without COVID-19 (controls). In all 3 models, comorbidities, female sex, and a younger age were significantly associated (p < 0.02) with a higher risk of contracting COVID-19. Patients receiving natalizumab as last DMT (OR [95% CI]: 2.38 [1.66-3.42], p < 0.0001) and those who underwent an escalation treatment strategy (1.57 [1.16-2.13], p = 0.003) were at significantly higher COVID-19 risk. Moreover, PwMS receiving their last DMT requiring hospital access (1.65 [1.34-2.04], p < 0.0001) showed a significant higher risk than those taking self-administered DMTs at home. DISCUSSION: This case-control study embedded in the IMSR showed that PwMS at higher COVID-19 risk are younger, more frequently female individuals, and with comorbidities. Long-lasting escalation approach and last therapies that expose patients to the hospital environment seem to significantly increase the risk of SARS-CoV2 infection in PwMS. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that among patients with MS, younger age, being female individuals, having more comorbidities, receiving natalizumab, undergoing an escalating treatment strategy, or receiving treatment at a hospital were associated with being infected with COVID-19. Among patients with MS who were infected with COVID-19, a severe course was associated with increasing age and having a progressive form of MS, whereas not being on treatment or receiving an interferon beta agent was protective.


Subject(s)
COVID-19/epidemiology , Immunosuppressive Agents/therapeutic use , Multiple Sclerosis/epidemiology , Adult , Age Factors , Case-Control Studies , Dimethyl Fumarate/therapeutic use , Female , Fingolimod Hydrochloride/therapeutic use , Glatiramer Acetate/therapeutic use , Humans , Interferon-beta/therapeutic use , Italy/epidemiology , Male , Middle Aged , Multiple Sclerosis/drug therapy , Multiple Sclerosis, Chronic Progressive/drug therapy , Multiple Sclerosis, Chronic Progressive/epidemiology , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Multiple Sclerosis, Relapsing-Remitting/epidemiology , Natalizumab/therapeutic use , Odds Ratio , Risk Factors , SARS-CoV-2 , Severity of Illness Index , Sex Factors , Time Factors
11.
Mult Scler Relat Disord ; 57: 103448, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1549997

ABSTRACT

BACKGROUND: Ocrelizumab maintains B-cell depletion via six-monthly dosing. Whilst this controls relapsing multiple sclerosis, it also inhibits seroconversion following SARS-CoV-2 vaccination unlike that seen following alemtuzumab and cladribine treatment. Emerging reports suggest that 1-3% B-cell repopulation facilitates seroconversion after CD20-depletion. OBJECTIVE: To determine the frequency of B-cell repopulation levels during and after ocrelizumab treatment. METHODS: Relapse data, lymphocyte and CD19 B-cell numbers were obtained following requests to clinical trial data-repositories. Information was extracted from the phase II ocrelizumab extension (NCT00676715) trial and the phase III cladribine tablet (NCT00213135) and alemtuzumab (NCT00530348/NCT00548405) trials obtained clinical trial data requests RESULTS: Only 3-5% of people with MS exhibit 1% B-cells at 6 months after the last infusion following 3-4 cycles of ocrelizumab, compared to 50-55% at 9 months, and 85-90% at 12 months. During this time relapses occurred at consistent disease-breakthrough rates compared to people during standard therapy. In contrast most people (90-100%) exhibited more than 1% B-cells during treatment with either cladribine or alemtuzumab. CONCLUSIONS: Most people demonstrate B cell repletion within 3 months of the last treatment of alemtuzumab and cladribine. However, few people repopulate peripheral B-cells with standard ocrelizumab dosing. Controlled studies are warranted to examine a view that delaying the dosing interval by 3-6 months may allow more people to potentially seroconvert after vaccination.


Subject(s)
COVID-19 , Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , Alemtuzumab/therapeutic use , Antibodies, Monoclonal, Humanized , COVID-19 Vaccines , Cladribine , Humans , Multiple Sclerosis/drug therapy , Multiple Sclerosis, Relapsing-Remitting/drug therapy , SARS-CoV-2 , Vaccination
12.
Hum Vaccin Immunother ; 17(11): 4345-4362, 2021 Nov 02.
Article in English | MEDLINE | ID: covidwho-1475712

ABSTRACT

Traditionally, the management of active relapsing remitting MS was based on the, so-called, maintenance therapy, which is characterized by continuous treatment with particular disease modifying therapy (DMT), and a return of disease activity when the drug is discontinued. Another approach is characterized by a short treatment course of a DMT, which is hypothesized to act as an immune reconstitution therapy (IRT), with the potential to protect against relapses for years after a short course of treatment. Introduction of monoclonal antibodies in the treatment of MS has revolutionized MS treatment in the last decade. However, given the increasingly complex landscape of DMTs approved for MS, people with MS and neurologists are constantly faced with the question which DMT is the most appropriate for the given patient, a question we still do not have an answer to. In this product review, we will discuss the first DMT that acts as IRT, an anti-CD52 monoclonal antibody alemtuzumab and an anti CD20 monoclonal antibody, ocrelizumab that has the potential to act as an IRT, but is administered continuously. Special emphasis will be given on safety in the context of COVID-19 pandemics and vaccination strategies.


Subject(s)
COVID-19 , Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , Alemtuzumab/adverse effects , Antibodies, Monoclonal , Antibodies, Monoclonal, Humanized , Humans , Immunologic Factors/adverse effects , Multiple Sclerosis/drug therapy , Multiple Sclerosis, Relapsing-Remitting/drug therapy , SARS-CoV-2
13.
Mult Scler ; 28(7): 1126-1130, 2022 06.
Article in English | MEDLINE | ID: covidwho-1443751

ABSTRACT

BACKGROUND: Despite impressive efficacy in immunocompetent individuals, the immunogenicity of a single dose of COVID-19 vaccine in B-cell-deplete patients remains unknown. OBJECTIVES: We aimed to quantify real-world vaccine immunogenicity in ocrelizumab recipients. METHODS: We measured post-vaccination SARS-COV-2 immunoglobulin G (IgG) in ocrelizumab recipients using a highly sensitive Luminex assay. RESULTS: 44.1% of patients had detectable SARS-COV-2-IgG 21+ days after one vaccine dose, regardless of vaccine type (AZD1222 vs BNT162b2, odds ratio (OR) = 0.62, 95% confidence interval (CI) = 0.157-2.32, p = 0.72). B-cell count strongly predicted seroconversion (ß1 = 12.38, 95% CI = 4.59-20.16, p = 0.0029), but undetectable B-cells did not preclude it. The second vaccine seroconverted 53% of the patients who had not already responded to dose 1. CONCLUSION: Humoral response after one COVID-19 vaccine dose is lower than expected in CD20-deplete patients.


Subject(s)
COVID-19 , Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , Antibodies, Monoclonal, Humanized , Antibodies, Viral , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines , ChAdOx1 nCoV-19 , Humans , Immunoglobulin G/therapeutic use , Multiple Sclerosis/drug therapy , Multiple Sclerosis, Relapsing-Remitting/drug therapy , SARS-CoV-2 , Seroconversion
14.
Mult Scler Relat Disord ; 56: 103283, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1440269

ABSTRACT

BACKGROUND: In accordance with expert guidance, patients have typically continued to receive treatment with subcutaneous interferon beta-1a (sc IFN ß-1a) for relapsing multiple sclerosis (MS) during the COVID-19 pandemic. METHODS: We provide a summary of outcomes among sc IFN ß-1a-treated patients with adverse events related to confirmed or suspected COVID-19, as reported to the Merck Global Patient Safety Database (as of 2 February 2021). Serious COVID-19-related adverse events (as classified by the reporting clinician) included those leading to hospitalization, admission to intensive care, or death. Outcomes were classified per usual pharmacovigilance practice. RESULTS: The evaluable cohort comprised 603 patients of median age 43 (range, 13-84) years and 75.1% were female. COVID-19 was experienced at a median of 33.0 (range, 0-321.8) months after start of treatment with sc IFN ß-1a. A total of 136 (22.6%) patients experienced serious COVID-19 events, including 59 hospitalizations (4 patients admitted to intensive care) and 5 deaths (fatality rate, 0.8%). Regarding non-fatal outcomes, 47.8% of patients (289/603) with COVID-19 adverse events were recovered or recovering at time of analysis; similar findings were apparent for the serious and hospitalized cohorts. CONCLUSION: Findings of this analysis from the Merck Global Patient Safety Database suggest that, compared with available statistics for the general population and those with MS, patients receiving sc IFN ß-1a for treatment of relapsing MS have relatively low rates of serious disease and/or severe outcomes with COVID-19.


Subject(s)
COVID-19 , Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , Adult , Female , Humans , Injections, Subcutaneous , Interferon beta-1a/adverse effects , Multiple Sclerosis/drug therapy , Multiple Sclerosis/epidemiology , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Multiple Sclerosis, Relapsing-Remitting/epidemiology , Pandemics , SARS-CoV-2 , Treatment Outcome
15.
Neurodegener Dis Manag ; 11(5): 387-409, 2021 10.
Article in English | MEDLINE | ID: covidwho-1394696

ABSTRACT

Teriflunomide, a once daily, oral disease-modifying therapy, has demonstrated consistent efficacy, safety and tolerability in patients with relapsing forms of multiple sclerosis (MS) and with a first clinical episode suggestive of MS treated up to 12 years. This review is an update to a previous version that examined data from the teriflunomide core clinical development program and extension studies. Data have since become available from active comparator trials with other disease-modifying therapies, treatment-related changes in brain volume (analyzed using structural image evaluation using normalization of atrophy) and real-world evidence including patient-reported outcomes. Initial data on the potential antiviral effects of teriflunomide in patients with MS, including case reports of patients infected with the 2019 novel coronavirus (SARS-CoV-2), are also presented.


Lay abstract Teriflunomide, a treatment taken orally once a day, has shown consistent effectiveness and safety in patients with relapsing forms of multiple sclerosis (MS). This review is an update to a previous version that summarized the trials from when teriflunomide was in clinical development for MS. Some of the newer studies described here compared teriflunomide with other MS treatments. Studies have shown positive effects of teriflunomide on brain volume; teriflunomide may also be effective against some viruses. People taking teriflunomide generally report stable cognition and quality of life, with no worsening of fatigue or disability. In the EU, teriflunomide has been recently approved for use in pediatric patients 10 years of age and above.


Subject(s)
Crotonates/therapeutic use , Hydroxybutyrates/therapeutic use , Immunosuppressive Agents/therapeutic use , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Nitriles/therapeutic use , Toluidines/therapeutic use , Brain/diagnostic imaging , Brain/pathology , Humans , Multiple Sclerosis, Relapsing-Remitting/diagnostic imaging , Multiple Sclerosis, Relapsing-Remitting/physiopathology , Organ Size
17.
J Neurol Sci ; 429: 117622, 2021 10 15.
Article in English | MEDLINE | ID: covidwho-1364275

ABSTRACT

Natalizumab effectively prevents disease activity in relapsing-remitting multiple sclerosis, but many treated patients report subjective wearing-off symptoms at the end of the 4-week interval between infusions. Extended interval dosing (EID) is a promising strategy to mitigate the risk of natalizumab-associated progressive multifocal leukoencephalopathy, but it is unknown whether EID affects wearing-off symptoms. In this observational study, we evaluated if prevalence or intensity of wearing-off symptoms changed when natalizumab dosing intervals were extended from 4 to 6 weeks in 30 treated patients during the outbreak of COVID-19 in Norway. New or increased wearing-off symptoms during EID were reported by 50%. Symptom increase was more frequent among patients with pre-existing wearing-off symptoms during standard dosing compared to patients without such pre-existing symptoms [p = 0.0005]. Our observations support the need to study the effect of EID on wearing-off symptoms in randomized controlled trials.


Subject(s)
COVID-19 , Leukoencephalopathy, Progressive Multifocal , Multiple Sclerosis, Relapsing-Remitting , Humans , Immunologic Factors/adverse effects , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Multiple Sclerosis, Relapsing-Remitting/epidemiology , Natalizumab/adverse effects , Pandemics , SARS-CoV-2
20.
Neurol Neuroimmunol Neuroinflamm ; 8(5)2021 09.
Article in English | MEDLINE | ID: covidwho-1311269

ABSTRACT

OBJECTIVE: To evaluate the clinical consequences of extended interval dosing (EID) of ocrelizumab in relapsing-remitting multiple sclerosis (RRMS) during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: In our retrospective, multicenter cohort study, we compared patients with RRMS on EID (defined as ≥4-week delay of dose interval) with a control group on standard interval dosing (SID) at the same period (January to December 2020). RESULTS: Three hundred eighteen patients with RRMS were longitudinally evaluated in 5 German centers. One hundred sixteen patients received ocrelizumab on EID (median delay [interquartile range 8.68 [5.09-13.07] weeks). Three months after the last ocrelizumab infusion, 182 (90.1%) patients following SID and 105 (90.5%) EID patients remained relapse free (p = 0.903). Three-month confirmed progression of disability was observed in 18 SID patients (8.9%) and 11 EID patients (9.5%, p = 0.433). MRI progression was documented in 9 SID patients (4.5%) and 8 EID patients (6.9%) at 3-month follow-up (p = 0.232). Multivariate logistic regression showed no association between treatment regimen and no evidence of disease activity status at follow-up (OR: 1.266 [95% CI: 0.695-2.305]; p = 0.441). Clinical stability was accompanied by persistent peripheral CD19+ B-cell depletion in both groups (SID vs EID: 82.6% vs 83.3%, p = 0.463). Disease activity in our cohort was not associated with CD19+ B-cell repopulation. CONCLUSION: Our data support EID of ocrelizumab as potential risk mitigation strategy in times of the COVID-19 pandemic. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with RRMS, an EID of at least 4 weeks does not diminish effectiveness of ocrelizumab.


Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/complications , Multiple Sclerosis, Relapsing-Remitting/complications , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Adult , Antigens, CD19 , B-Lymphocytes/immunology , Disability Evaluation , Female , Humans , Lymphocyte Count , Magnetic Resonance Imaging , Male , Middle Aged , Pandemics , Retrospective Studies , Treatment Outcome
SELECTION OF CITATIONS
SEARCH DETAIL