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1.
Front Immunol ; 12: 796482, 2021.
Article in English | MEDLINE | ID: covidwho-2123406

ABSTRACT

Background: Vaccination campaign to contrast the spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has raised the issue of vaccine immunogenicity in special populations such as people with multiple sclerosis (PwMS) on highly effective disease modifying treatments (DMTs). While humoral responses to SARS-CoV-2 mRNA vaccines have been well characterized in the general population and in PwMS, very little is known about cell-mediated responses in conferring protection from SARS-CoV-2 infection and severe coronavirus disease-2019 (COVID-19). Methods: PwMS on ocrelizumab, fingolimod or natalizumab, vaccinated with two doses of mRNABNT162b2 (Comirnaty®) vaccine were enrolled. Anti-Spike (S) and anti-Nucleoprotein (N) antibody titers, IFN-gamma production upon S and N peptide libraries stimulation, peripheral blood lymphocyte absolute counts were assessed after at least 1 month and within 4 months from vaccine second dose administration. A group of age and sex matched healthy donors (HD) were included as reference group. Statistical analysis was performed using GraphPad Prism 8.2.1. Results: Thirty PwMS and 9 HDs were enrolled. All the patients were negative for anti-N antibody detection, nor reported previous symptoms of COVID-19. Peripheral blood lymphocyte counts were assessed in PwMS showing: (i) reduction of circulating B-lymphocytes in PwMS on ocrelizumab; (ii) reduction of peripheral blood B- and T-lymphocyte absolute counts in PwMS on fingolimod and (iii) normal B- and T-lymphocyte absolute counts with an increase in circulating CD16+CD56+ NK-cells in PwMS on natalizumab. Three patterns of immunological responses were identified in PwMS. In patients on ocrelizumab, anti-S antibody were lacking or reduced, while T-cell responses were normal. In patients on fingolimod both anti-S titers and T-cell mediated responses were impaired. In patients on natalizumab both anti-S titers and T-cell responses were present and comparable to those observed in HD. Conclusions: The evaluation of T-cell responses, anti-S titers and peripheral blood lymphocyte absolute count in PwMS on DMTs can help to better characterize the immunological response after SARS-CoV-2 vaccination. The evaluation of T-cell responses in longitudinal cohorts of PwMS will help to clarify their protective role in preventing SARS-CoV-2 infection and severe COVID-19. The correlation between DMT treatment and immunological responses to SARS-CoV-2 vaccines could help to better evaluate vaccination strategies in PwMS.


Subject(s)
B-Lymphocytes/immunology , COVID-19 , Multiple Sclerosis/immunology , SARS-CoV-2/immunology , T-Lymphocytes/immunology , Vaccination , Adult , COVID-19/immunology , COVID-19/prevention & control , Female , Humans , Male , Middle Aged , Multiple Sclerosis/therapy
2.
J Neurol ; 2022 Oct 13.
Article in English | MEDLINE | ID: covidwho-2059820

ABSTRACT

BACKGROUND: Many patients treated with Natalizumab experience wearing-off symptoms (WoS) towards the end of the administration cycle. During the pandemic we advised and asked patients undergoing treatment with Natalizumab if they wanted to be shifted from a standard interval dosing (StID of 4 weeks) to an extended interval dosing (ExID of 5-6 weeks), regardless of their JCV index. Our main objective was to study prevalence and incidence of WoS when ExID was adopted. METHODS: We enrolled 86 patients, from May 2020 to January 2021, evaluated at baseline and during a 6 months follow-up with a survey focused on WoS, Fatigue Severity Scale (FSS), Expanded Disability Status Scale (EDSS) and MRI. RESULTS: Among the 86 patients, 32 (37.2%) reported WoS. Most common one was fatigue (93.7%). Mean EDSS was higher in the group reporting WoS (3.8 WoS vs 3.1 non-WoS, p < 0.05). Sphincterial function was the EDSS item that significantly differed between the WoS group and the non-WoS group (1.4 WoS vs 0.6 non-WoS, p < 0.001). WoS correlate with the FSS scale (p < 0.001). CONCLUSION: Adopting an extended interval dosing does not result in significantly different occurrence of WoS between the ExID and the StID populations, in our cohort of patients. Interestingly, there is a strong correlation between WoS and a higher EDSS and FSS. Safety and efficacy of Natalizumab with ExID are relatively preserved in our study.

3.
Multiple Sclerosis and Related Disorders ; 59, 2022.
Article in English | EMBASE | ID: covidwho-2004365

ABSTRACT

Background: Recent Covid-19 outbreak around the world turned into an international public health concern. Generally, people who receives immunosuppressive treatments or have an underlying disease are more likely to be infected. Multiple sclerosis (MS) patients also may have higher risk of infection due to the taking immunosuppressive or immunomodulatory drugs. Our objectives were to identify the epidemiological characteristics of Covid-19 in patients with MS for improve quality of care and achievement to better diagnosis and treatment in MS patients in Iran. Material(s) and Method(s): The present data were obtained from a hospital-based registry in Imam Khomeini hospital, Tehran, Iran. Totally, 88 MS patients who was infected by Covid-19 were registered from May, 2020 to March 2021. Demographic and clinical data was collected (2). Result(s): 55 (65.5%) of participants were female by the mean age (SD) of 37.48 ± 10.05 years. Covid-19 diagnosis of 4 (4.5%) of patients was based on positive PCR test. The most MS treatment was receiving by patients was Rituximab (20 (22.7%)) following by Dimethyl Fumarate (14 (15.9%)), Fingolimod (10 (11.4%)), Glatiramer acetate (8 (9.1%)), Interferon β-1a (IM) (5 (5.7%)), Interferon β-1a (SQ) (5 (5.7%)), Interferon β-1b (3 (3.4%)), Triflunomide (2 (2.3%)) and Natalizumab (1 (1.1%)). The mean (SD) interval from the last Rituximab injection to Covid-19 infection was 3.80 ± 3.40 months. 37 (42.0%) MS patients continued to take their drugs after Covid-19 infection, while 10 (11.4%) of them stopped taking MS medicine and 7 (8.0%) of them was taking no treatment for controlling MS. 2 (2.3%) of participants was diagnosed by MS after Covid-19 infection. 9 (9.7%) subjects hospitalized due to Covid-19 infection. The mean (SD) duration of hospitalization was 5 ± 7.81 days. One (1.1%) death cases was reported. Conclusion(s): Our findings revealed valuable data of Covid-19 characteristics in patients with MS which could be useful for improving health services for MS patients during the Covid-19 pandemic (3-4).

4.
Multiple Sclerosis and Related Disorders ; 59, 2022.
Article in English | EMBASE | ID: covidwho-2004356

ABSTRACT

Background: Vaccines to prevent SARS-CoV-2 infection are considered the most promising approach for curbing the pandemic. There are many concerns about the effectiveness of vaccination in patients with multiple sclerosis (MS). Few studies have examined the effectiveness of mRNA COVID vaccine in MS patients treated with high potency disease modifying therapies (DMTs). The aim of this study was to evaluate the efficacy of BBIBP-CorV (Sinopharm) vaccine in patients treated with 7 different DMTs. Material(s) and Method(s): This quasi-experimental study was conducted on the patients of MS clinics of Imam Hossein hospital in Tehran (capital of Iran) and Ghaem hospital in Mashhad (northeast of Iran). MS patients with:1- no history of COVID infection in the past 6 month, 2- no history of relapse or steroid use in the past 4 weeks, 3- regular use of a DMT for at least 6 months (9 month for glatiramer acetate) and 4- at least 2 months interval between the previous rituximab infusion and vaccination, were enrolled and vaccinated with Sinopharm vaccine (2 doses, 4 weeks apart). In the case of relapse, COVID infection, or If any of the antibodies (anti neucleocapsid IgM and IgG and anti RBD IgG) were positive at the first injection of the vaccine, the patient was excluded from the study. The amount of IgG class antibodies against virus RBD were measured using ELISA SARS-CoV-2 IgG DIAZIST after 28 days of the first vaccination and on the day 56 (28 days after the second vaccination). An index value higher than 1.1 was considered reactive for anti RBD antibodies. Result(s): Out of the 208 patients included in the study, 91 patients were excluded and 117 patients were finally analyzed. Humoral response to vaccination based on the DMT used by the patient was as follows: beta interferons: 89.47% (17 out of 19 patients), dimethyl fumarate: 85.71% (12 out of 14 patients), patients without DMT treatment:83.33% (5 out of 6 patients), Natalizumab 83.33% (5 out of 6 patients), glatiramer acetate:71.42% (5 out of 7 patients), teriflunomide: 50% (4 out of 8 patients), rituximab: 38.46% (15 out of 39 patients), and fingolimod: 21.05% (4 out of 19 patients). Conclusion(s): According to our findings, the response to vaccination is maintained in patients treated with beta interferons, dimethyl fumarate and natalizumab, but is less than acceptable in patients treated with rituximab and fingolimod.

5.
Biomedica ; 42:1-46, 2022.
Article in English | Web of Science | ID: covidwho-2003382

ABSTRACT

Neuroimmunology is a discipline that increasingly broadens its horizons in the understanding of neurological diseases. At the same time and in front of the pathophysiological links of neurological diseases and immunology, specific diagnostic and therapeutic approaches have been proposed. Despite the important advances in this discipline, there are multiple dilemmas that concern and filter into clinical practice. This article presents 15 controversies and a discussion about them, which are built with the most up-to-date evidence available. The topics included in this review are: steroid decline in relapses of multiple sclerosis (MS), therapeutic recommendations in MS in light of the SARS-CoV2 pandemic, evidence of vaccination in MS and other demyelinating diseases, overview current situation of isolated clinical and radiological syndrome, therapeutic failure in MS as well as criteria for suspension of disease-modifying therapies, evidence of the management of mild relapses in MS, recommendations for prophylaxis against strongyloides stercolaris, usefulness of a second course of immunoglobulin in the syndrome Guillain-Barre (GBS), criteria to differentiate an acute-onset inflammatory demyelinating chronic polyneuropathy versus GBS and the utility of angiotensin-converting enzyme in neurosarcoidosis. In each of the controversies, the general problem is presented and specific recommendations are offered that can be adopted in daily clinical practice.

6.
European Journal of Neurology ; 29:281, 2022.
Article in English | EMBASE | ID: covidwho-1978452

ABSTRACT

Background and aims: Social distancing measures during the Covid-19 pandemic reduced access to health care and concerns were raised over the safety of immunosuppressive disease modifying treatments (DMT) for multiple sclerosis (MS). Here, we aimed to investigate changes in DMT prescription before and during the pandemic in a large and well-characterized real-world cohort of MS patients. Methods: From the Vienna MS database (VMSD) we extracted MS patients who were initiated on a new DMT (both treatment-naïve and switching) between January 1st 2017 and December 31st 2021. Two time periods were defined: 1) the preCovid-19 era (January 1st 2017 to March 15th 2020, i.e. the day of the first lockdown in Austria) and the Covid-19 era (March 16th 2020 to December 31st 2021). Average annualized DMT prescription rates were descriptively compared between the two periods. Results: The average annualized number of prescriptions in the preCovid-19 era was 90.3/year and dropped to 74.8/year (-17.2%) in the Covid-19 era, driven by a marked reduction to 41.7/year (-54%) in the first nine months of the Covid-19 era, partly offset by a rise to 101 in 2021. Use of alemtuzumab (-64%), antiCD20 (-49%), cladribine (-46%), and S1PM (-38%) was reduced, while natalizumab increased by 24%. Lower efficacy treatments remained stable. Conclusion: The pandemic coincides with a drop in DMT prescription, most markedly for immunosuppressive highefficacy treatments, strongly suggesting the pandemic as the causal factor. If and how much this affects long-term outcome is yet to be determined. (Figure Presented).

7.
Clinical and Experimental Neuroimmunology ; 2022.
Article in English | EMBASE | ID: covidwho-1968077

ABSTRACT

Various effective monoclonal antibodies (mAbs) have been approved for both multiple sclerosis (MS) and anti-aquaporin-4-seropositive neuromyelitis optica spectrum disorders worldwide, including in Japan. As these newer mAbs have distinct modes of action that effectively suppress the recurrence of inflammation and slow disability progression, they can modulate and interfere with the protective immune response against pathogens, resulting in various infectious complications. Among various mAbs, natalizumab (NTZ) has the highest risk of causing progressive multifocal leukoencephalopathy (PML), a rare but fatal opportunistic brain infection caused by John Cunningham polyomavirus. Switching from NTZ to B-cell-depleting mAbs, such as ocrelizumab, is also a possible risk factor for PML development. Alemtuzumab carries the risk of reactivation of varicella-zoster virus (VZV);therefore, prophylactic acyclovir treatment is required. NTZ has also been associated with VZV reactivation. Eculizumab can cause severe meningococcal infection due to Neisseria meningitis, and vaccination prior to treatment induction is required. Attention to the reactivation of hepatitis B or Mycobacterium tuberculosis is also needed during mAb therapy. Additionally, in the era of severe acute respiratory syndrome coronavirus 2 infection (COVID-19), the risk for of developing severe COVID-19 may be associated with some mAbs, such as B-cell-depleting agents. Thorough understanding and mitigation strategies for infectious risks are essential.

8.
Neurology ; 98(18 SUPPL), 2022.
Article in English | EMBASE | ID: covidwho-1925535

ABSTRACT

Objective: To assess symptoms, severity, outcome of Covid 9 in Multiple sclerosis patients ( including NeuroMyelitis Optica )and to assess the prognostic factors for severe Covid19 Background: Covid 19 pandemic came with its own challenges of novelty, lack of information uncertainty of treatment and its effect on chronic autoimmune diseases like Multiple sclerosis. The outcome of covid 19 with immunosuppressive and immunomodulatory treatment in multiple sclerosis was not known till this year. We share our observation of multiple sclerosis patients including neuromyelitis optics who contracted Covid 19 in Dubai UAE, during April 2020 to Sep 2021 in 2 major hospitals treating multiple sclerosis. Design/Methods: All Multiple sclerosis Patients following in Rashid hospital and Alzahra Hospital Neurology apartment who had Covid 19 were included in this observational study. Results: 55 MS patient with Covid 19 ( including 2 NMO) were studied. Age of the patients ranged from 19 to 58years. There were 39 females and 16 males. 43 were RRMS, 6 -SPMS,4- CIS, 1- PPMS and 2 NMOSD. 6 were on interferons, 2 on teriflunamide, 8 on dimethylfumarate, 12 on fingolimod, 3 on natalizumab, 1 on alemtuzumab, 1 on rituximab, 9 on cladribine, 12 on ocrelizumab and 1 on azathioprine. 47 had fever, 30 anosmia, 28 had fatigue and 42 had sorethroat and cough, 5/55 had pneumonia.39/55 had mild covid, 13/55 had moderate and 3 had severe covid 19. 3/55 needed ICU. There were 2 deaths, first with MS, EDSS 6.5 on ocrelizumab and second with NMO (EDSS 7.0)on rituximab Conclusions: The disease course and outcomes were mostly favorable with most patients not requiring hospitalization. A higher EDSS score, progressive disease, use of rituximab, and ocrelizumab(antiCD20 therapy) were associated with the mortality encountered. Age, sex, smoking history, and duration of MS were not independent risk factors for increased severity or adverse COVID-19 disease outcomes.

9.
Neurology ; 98(18 SUPPL), 2022.
Article in English | EMBASE | ID: covidwho-1925472

ABSTRACT

Objective: To examine the temporal trends of humoral and cell-mediated immune responses to SARS-CoV-2 mRNA vaccines among multiple sclerosis (MS) patients on different immunomodulatory therapies. Background: The impact of various MS medications on the immune responses to SARS-CoV-2 vaccine is of acute interest to patients and clinicians. Design/Methods: 22 MS patients treated with ocrelizumab (OCR, n=9), natalizumab (NTZ, n=8), fumarates (FUM, n=5;diroximel fumarate, 3 and dimethyl fumarate, 2) received BNT162b2 (Pfizer, n=15) or mRNA-1273 (Moderna, n=7) vaccines. Blood samples were collected before and after each of the two vaccine doses, and 2 months after second vaccine dose. AntiSARS-CoV-2 spike protein titers were measured using quantitative assay (Labcorp). Antibody neutralization was measured with a lentivirus-based pseudovirus particle expressing the D614 spike protein (Labcorp-Monogram Biosciences). T-cell reactivity was determined by measuring interferon-gamma and interleukin-2 in response to stimulation with SARS-CoV-2 peptides. Results: All patients in NTZ and FUM cohorts, but only 22% (2/9) of OCR cohort developed anti-spike and neutralizing antibodies. The highest titers were measured after the second vaccine dose, without significant difference between the NTZ and FUM cohorts in anti-spike IgG (69.7+/-55.1 vs 56.0+/-36.7 arbitrary units/ml) or neutralizing ID50 (1513+/-1317 vs 942+/ -566). Two months after the second vaccine, the antibody titers and neutralizing ID50 decreased by 72% and 79% in NTZ cohort, respectively, and by 45% and 49% in FUM cohort. T-cell reactivity was observed in all cohorts as early as 7 days after the first vaccine, and further increased following the second vaccine. Conclusions: Patients on NTZ and FUM mounted robust antibody responses to SARS-CoV-2 mRNA vaccines, in contrast to OCR-treated patients. T-cell responses were comparable among all three treatment cohorts. Two months after the second vaccine, the serological responses decreased by 45-79%. These findings may inform the optimal timing of additional vaccine doses for MS patients.

10.
Neurology ; 98(18 SUPPL), 2022.
Article in English | EMBASE | ID: covidwho-1925248

ABSTRACT

Objective: To examine response of SARS-CoV-2 vaccination in patients with MS (pwMS) by a systematic review. Background: Varying responses to the SARS-CoV-2 vaccines have been reported in pwMS on disease modifying therapies (DMTs). We performed a meta-analysis and systematic review of pwMS and rates of immune response to SARS-CoV-2 vaccines by DMT and by vaccine type. Design/Methods: A systematic review was conducted for manuscripts from January 1, 2019 until October 1, 2021 by two independent reviewers (M.D. and G.G.). Search terms in PubMed, Google Scholar and Embase included “multiple sclerosis,” “SARS-CoV-2”, “Coronavirus-19”, “vaccines”, and “vaccinations.” Data from publications reporting on antibody or cellular vaccine response data in pwMS were included. Antibody response was defined as positive or negative, based upon assay cutoffs. Immune response to prior COVID infections were excluded. Descriptive statistics was performed using STATA. Results: We included 16 out of 589 articles and 186 healthy controls and 1,239 pwMS. Protective antibody responses were detected in 99% of healthy controls (184/186), 100% untreated pwMS (169/169), 99% pwMS on beta-interferons (79/80), and 100% pwMS on glatiramer acetate (39/39), dimethyl fumarate (116/116), natalizumab (127/127), alemtuzumab (19/19), and teriflunomide (72/72). Ninety-three percent of pwMS on cladribrine (69/74), 70% of sphingosine 1-phosphate modulators (S1PM) (108/155) and forty-six percent of pwMS on anti-CD20 treatments had an antibody response (177/388). PwMS on rituximab had a higher antibody response (23/37 = 62%) as compared to ocrelizumab (107/205 = 39%), with unknown anti-CD20 in 76. This difference may be attributable to the vaccination received (mRNA-1273 vs BNT162b2) as mRNA-1273 results in higher antibodies. However, 46/49 (94%) on anti-CD20 had T cell responses to SARS-CoV-2 vaccines. Conclusions: Varying rates of vaccine response are reported in pwMS. Humoral responses appear to be blunted in S1PM and anti-CD20 treatments;however, the majority develop cellular responses. Further investigation into how DMT affects immune response are needed.

11.
Neurology ; 98(18 SUPPL), 2022.
Article in English | EMBASE | ID: covidwho-1925235

ABSTRACT

Objective: To compare the risk of SARS-CoV-2 infection before and after mass vaccination among patients with multiple sclerosis (pwMS) taking different disease-modifying therapies (DMTs) compared to the general population (GP). Background: Real-world data in the GP show that SARS-CoV-2 vaccines are effective in preventing infections, but it is still unclear whether vaccination offers the same level of protection for pwMS taking immunomodulatory DMTs. Design/Methods: National Health Service (NHS) England and NHS Improvement (NHSE/I) hold prescribing data on all MS DMTs in England. Public Health England (PHE) collected data on all SARS-CoV-2 tests in England. Datasets of NHE/I and PHE were merged to estimate the monthly rates of SARS-CoV-2 infections in the entire population of pwMS taking DMTs in England. Publicly available data were used for the same analysis in the GP. The relative risk (RR) of infection in pwMS taking DMTs compared to the GP was calculated during two waves of the pandemic: before (November 2020-January 2021) and after (July-September 2021) mass vaccination. Results: All 42,402 pwMS taking DMTs in England were included. A total of 28,113 (66.3%) patients were tested for SARS-CoV-2 out of whom 4,104 (14.6%) tested positive. Pre-vaccination, the RR (95%CI) of infection was beta-interferon: 0.75(0.65-0.87), cladribine: 0.93(0.75-1.14), dimethyl fumarate: 1.15(1.05-1.25), fingolimod: 0.88(0.76-1.02), glatiramer acetate: 1.05(0.93-1.19), natalizumab: 1.08(0.96-1.21), ocrelizumab: 1.20(1.07-1.34), teriflunomide 0.79(0.63-0.99). Post-vaccination, it was beta-interferon: 0.73(0.63-0.85), cladribine: 1.21(1.02-1.45), dimethyl fumarate: 1.34(1.24-1.45), fingolimod: 1.63(1.47-1.82), glatiramer acetate: 0.85(0.74-0.98), natalizumab: 1.22(1.10-1.36), ocrelizumab: 2.18(2-2.36), teriflunomide: 1.04 (0.85-1.27). Conclusions: The risk of SARS-CoV-2 infection in patients taking ocrelizumab and fingolimod substantially increased compared to the general population following vaccination which agrees with the suppressed humoral immune response observed with these DMTs. The changes associated with other DMTs are less clear. Further analysis of data collected longitudinally over a longer period will reveal their impact on the effectiveness of SARS-CoV-2 vaccines.

12.
Drugs of the Future ; 46(12):1037-1039, 2021.
Article in English | EMBASE | ID: covidwho-1854921

ABSTRACT

This year's ECTRIMS brought scientists and specialists together to discuss developments in multiple sclerosis (MS), including how to define and monitor disease progression, imaging pathology, and, of course, the impact of the COVID-19 pandemic on MS patient care.

13.
Mult Scler Relat Disord ; 57: 103345, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1851824

ABSTRACT

COVID-19 pandemic represented a challenge in the management of treatments for Multiple Sclerosis (MS), such as Natalizumab (NTZ). NTZ interferes with the homing of lymphocytes into the central nervous system, reducing immune surveillance against opportunistic infection. Although NTZ efficacy starts to decline 8 weeks after the last infusion, increasing the risk of disease reactivation, evidence is lacking on the safety of reinfusion during active SARS-CoV-2 infection. We report clinical outcomes of 18 pwMS receiving NTZ retreatment during confirmed SARS-CoV-2 infection. No worsening of infection or recovery delay was observed. Our data supports the safety of NTZ redosing in these circumstances.


Subject(s)
COVID-19 , Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , Humans , Immunologic Factors/adverse effects , Multiple Sclerosis/drug therapy , Multiple Sclerosis/epidemiology , Multiple Sclerosis, Relapsing-Remitting/epidemiology , Natalizumab/adverse effects , Pandemics , SARS-CoV-2
14.
World J Pharm Pharm Sci ; 10(11): 14-22, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1801617

ABSTRACT

Monoclonal antibodies (mAbs) are increasingly being prescribed to patients and investigated in the field of medicine and research. This class of medication is unique due to its ability to be engineered into targeting a specific receptor. Numerous studies and reviews have reported the efficacy, potency, and clinical usage of mAbs in the treatment of a variety of diseases ranging from autoimmune disorders to malignant cancers. However, very few publications classify and provide a brief synopsis of mAbs that includes their pharmacological profiles. mechanisms of action, uses, and side effects in a concise manner. Therefore, this review aims to classify the current mAbs drugs used in clinical practice according to system diseases by providing a brief summary for each of them. For example, regarding cardiovascular disorders, mAbs such as Abciximab, Bevacizumab, and Digoxin Immune Fab will be reviewed. Denosumab, used to treat musculoskeletal disorders, will be also discussed. In addition, mAbs such as Adalimumab, Eculizumab, Natalizumab used in autoimmune disorders and Alemtuzumab, Trastuzumab, Cetuximab, and Rituximab that are prescribed for tumors will be reviewed. Finally, we shall discuss two mAbs that are IL-6 antagonists, Tocilizumab and Siltuximab, which are in ongoing clinical trials as potential treatments of COVID-19. The mAbs have profound benefits against chronic and malignant conditions, and the overall purpose of this review is to illustrate the basic pharmacological profiles of mAbs that physicians may find useful in establishing their management protocols.

15.
Multiple Sclerosis Journal ; 28(2):NP10, 2022.
Article in Spanish | EMBASE | ID: covidwho-1724264

ABSTRACT

Introduction: Hasta la fecha existe escasa información sobre la eficacia de las vacunas contra SARS-CoV-2 en pacientes con esclerosis múltiple (pEM). Objetives: Nuestro objetivo fue evaluar la respuesta humoral a las vacunas contra SARS-CoV-2 en pEM bajo drogas modificadoras de la enfermedad (DME) de alta eficacia. Methods: Se midió IgG del SARS-CoV-2 utilizando serología basada en proteínas anti-spike y anti-nucleocápside basal y al mes de la segunda dosis de las vacunas BNT162b2-COVID-19 o CoronaVac. Se midió el valor absoluto (VA) del título de anticuerpos IgG anti-spike (IgGsp) y IgG anti-nucleocápside (IgGnc). Se definió respuesta humoral protectora (RHP) a títulos post vacuna > 1.0. Se compararon 4 grupos: pEM bajo tratamiento con cladribina, anti-CD20 (rituximab u ocrelizumab), alemtuzumab y se utilizó como grupo control a pEM sin tratamiento o bajo terapias inyectables (interferon o acetato de glatiramer). Results: Se incluyeron 16 (15%) y 90 (85%) pEM vacunados con BNT162b2-COVID-19 y CoronaVac respectivamente. Presentaron RHP IgGsp el 72.6%, 80%, 91.7%, 17.2% y 96.7%, en el total (N) de pacientes evaluados (106): grupo control (15), alemtuzumab (12), anti CD20 (29) y cladribina (30). Presentaron RHP IgGnc el 39.5%, 40%, 60%, 14.3% y 38.5% en el total de pacientes evaluados (38): grupo control (5), alemtuzumab (5), anti CD20 (7) y cladribina (13). Los VA de títulos de anticuerpos IgGsp fueron significativamente más bajos en los pEM en tratamiento con antiCD20 (7.42 ± 30.9) en comparación al grupo control (296.2 ± 640.9;p<0.01), cladribina (198.4 ± 399.9;p<0.01) y alemtuzumab (409.4 ± 717.8;p<0.01). Los pEM antiCD20 presentaron menor RHP IgGsp que cladribina (p<0.01) y alemtuzumab (p<0.01). No se encontraron diferencias significativas en el tiempo desde la última dosis entre los pEM antiCD20, cladribina y alemtuzumab (p=0.06). Hubo diferencias significativas entre menor edad y menor EDSS con RHP IgGsp (p=0.03 y p<0.01 respectivamente). Sin diferencias con el tipo de vacuna y tiempo desde la última. En el modelo de regresión logística sólo EDSS resultó ser un predictor significativo en RHP IgGsp (OR 0.50, IC95% 0.42 -0.83). Conclusions: Se encontró menor RHP IgGnc en comparación con IgGsp en todos los grupos evaluados. RHP IgGsp es menor en los pacientes con terapias anti CD20 y se desarrolla en terapias como cladribina, alemtuzumab y natalizumab, independiente de su última administración. Se requieren estudios de función de células T para los diferentes grupos, en especial antiCD20 para evaluar eficacia global de las vacunas.

16.
Developmental Medicine and Child Neurology ; 64(SUPPL 1):22, 2022.
Article in English | EMBASE | ID: covidwho-1723132

ABSTRACT

Objective: Paediatric neurologists are concerned about the risk of COVID-19 in children with demyelinating disorders receiving immunomodulatory treatment. To investigate this, we collected data via the UK Childhood Neuro-Inflammatory Disorders (UK-CNID) network of the British Paediatric Neurology Association (BPNA). Methods: Survey of paediatric neurologists managing unvaccinated UK children (<18 years) with a demyelinating disorder (multiple sclerosis [MS];neuromyelitis optica spectrum disorder [NMOSD] and myelin oligodendrocyte glycoprotein antibody disease [MOGAD]) on immunomodulatory therapy with SARS-CoV-2 infection confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) of nasopharyngeal swabs between March and December 2020. Results: Of 151 UK children (MS 98, MOGAD 37, NMOSD 16) with a median age of 9 years (range 6-18y), with a demyelinating disorder, nine (6.0%) had a positive PCR for SARS-CoV-2. Five had MS and four MOGAD. Four were from south Asian or south-east Asian, four were White and one was mixed White and south Asian. Seven children had COVID-19 symptoms;two were asymptomatic. Two required a brief hospital admission for typical COVID-19 respiratory symptoms and the remaining five had mild symptoms including fever, rash, cough and headache. One with MOGAD, treated with azathioprine, developed transverse myelitis 12 days after COVID-19 onset. She recovered fully with a course of corticosteroids. MS patients were on following disease modifying therapies;dimethylfumarate (n=2), fingolimod (n=1);natalizumab (n=1) and ocrelizumab (n=1). MOGAD cases were on the following immune therapy: combination of oral prednisolone and intravenous immunoglobulin (n=2), prednisolone steroids (n=1) and azathioprine (n=1). Conclusions: In contrast to adult patients, who often have underlying co-morbidities and advanced neurological disabilities, we have identified that children treated for demyelinating disorders appear to have a milder COVID-19 course. Whilst the number of children treated for demyelinating disorders that developed COVID-19 is low, the overall mild course described may provide reassurance to neurologists, patients and family members.

17.
Neurol Sci ; 43(5): 2947-2949, 2022 May.
Article in English | MEDLINE | ID: covidwho-1694524

ABSTRACT

BACKGROUND: Few studies investigated the immune response to SARS-CoV-2 vaccine in patients with multiple sclerosis (pwMS) treated with natalizumab (NTZ) and found a short-term efficient humoral response; however, there are no studies assessing the levels of SARS-CoV-2 IgG antibodies in pwMS treated with NTZ over time. METHODS: Humoral immune response to BNT162b2 mRNA COVID-19 vaccine was assessed in a group of 26 pwMS on NTZ up to 6 months after a full COVID-19 vaccination cycle and compared it with 43 age- and sex-matched group of HC. Serum samples were collected before the first dose (T0), and 4 weeks (T1) and 6 months (T2) after the first dose of BNT162b2 mRNA COVID-19 vaccine. The LIAISON® SARS-CoV-2 TrimericS-IgG assay (DiaSorin-S.p.A.) was employed for the detection of IgG antibodies to SARS-CoV-2 spike protein (cutoff for positive IgG antibodies: 33.8 BAU/mL). RESULTS: At T1 and T2, both groups showed an efficient humoral response to BNT162b2 mRNA COVID-19 vaccine. A significant reduction of IgG antibodies to SARS-CoV-2 spike protein was detected at T2 both in pwMS and in HC, but SARS-CoV-2 IgG antibodies were still above the cutoff limit in all participants. CONCLUSIONS: pwMS on NTZ develop and maintain a long-term humoral response after a full COVID-19 vaccination cycle comparable to their healthy peers, and these findings are relevant for clinicians called to counsel about COVID-19 mRNA vaccine timing and booster doses in pwMS treated with NTZ.


Subject(s)
COVID-19 , Multiple Sclerosis , Antibodies, Viral , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines/therapeutic use , Humans , Immunoglobulin G , Multiple Sclerosis/drug therapy , Natalizumab/therapeutic use , RNA, Messenger , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Vaccines, Synthetic , mRNA Vaccines
18.
Ideggyogy Sz ; 74(11-12): 413-424, 2021 Nov 30.
Article in Hungarian | MEDLINE | ID: covidwho-1689683

ABSTRACT

Multiple sclerosis (MS) is typically a disease of young adults. Childhood MS can be defined in patients under 18 years of age, although some authors set the limit un-der the age of 16 formerly known as "early-onset multiple sclerosis" or "juvenile multiple sclerosis", seen in 3-5% of all MS patients. Nowadays, owing to ever-evolving, better diagnostic tools and well-traced, strictly defined diagnostic criteria, childhood MS is showing an increasing incidence worldwide (0.05-2.85/100 000). MS is characterized by recurrent episodes of the central nervous system with demyelination separated in space and time. In childhood almost exclusively the relapsing-remitting (RR) type of MS occurs. Based on experience in adults, the goal in the pediatric population is also the early diagnosis, to initiate adequate DMT as soon as possible and to achieve symptom relief and good quality of life. Based on efficacy and safety studies in the adult population, inter-feron ß-1a and glatiramer acetate were first approved by the FDA and EMA for the treatment of childhood MS also. The increased relapse rate and rapid progression of childhood MS and unfavorable therapeutic response to nearly 45% of the first DMT necessitated the testing of more effective and second-line drugs in the population under 18 years of age (PARADIGMS, CONNECT). Although natalizumab was reported to be effective and well-tolerated in highly active RRMS in childhood, evidence based studies were not yet available when our patients' treatment started. In this article, we report on the successful treatment of three active RRMS patients with individually authorized off-label use of natalizumab.


Subject(s)
Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , Adolescent , Child , Glatiramer Acetate/therapeutic use , Humans , Multiple Sclerosis/diagnosis , Multiple Sclerosis/drug therapy , Natalizumab/therapeutic use , Quality of Life , Young Adult
19.
BMC Neurol ; 21(1): 462, 2021 Nov 29.
Article in English | MEDLINE | ID: covidwho-1542105

ABSTRACT

BACKGROUND: The Coronavirus disease 2019 (COVID-19) caused by the new Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has become a pandemic, affecting the therapeutic management for Multiple Sclerosis (MS). Any decision regarding the discontinuation of high-potency agents for moderate and highly active MS should be carefully evaluated, taking into account the potential risk of rebound of the disease. In particular, no data about clinical outcome of patients with MS receiving Natalizumab (NTZ) during active COVID-19 infection have been reported yet. CASES PRESENTATION: We reported on 6 patients treated with NTZ for relapsing MS during active COVID-19 infection, who recovered without reporting any worsening or new symptoms. Most of the patients were asymptomatic, with the exception of one patient who had a slight worst COVID-19 clinical course. No patients received O2-therapy or required intensive care. No neurological complications were observed. CONCLUSIONS: This paper reported the clinical outcome of patients with MS receiving NTZ during active COVID-19 infection. This case series suggests that treatment with NTZ during pandemic is relatively safe and might be continued in selected patients who are infected by COVID-19, thereby reducing the risk of MS disease rebound.


Subject(s)
COVID-19 , Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , Humans , Multiple Sclerosis/drug therapy , Multiple Sclerosis/epidemiology , Natalizumab/adverse effects , SARS-CoV-2
20.
Mult Scler Relat Disord ; 57: 103382, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1540873

ABSTRACT

BACKGROUND: The COVID-19 epidemic raises important questions about the efficacy of vaccines for people treated with ocrelizumab, an anti-CD20 therapy. Ocrelizumab has been shown to reduce the humoral response to SARS-CoV-2 infection and vaccination, but the T-cell response to vaccination has not been fully characterized. We sought to provide data regarding B and T-cell mediated responses to SARS-CoV-2 vaccination in ocrelizumab-treated patients, and to determine what variables correlate with vaccine immunogenicity. We hypothesized that patients without a humoral response to SARS-CoV-2 vaccination would still have intact T-cell responses. METHODS: We conducted a prospective, observational, single center cohort study of patients with MS treated with either ocrelizumab or natalizumab as a comparator between March 2, 2021, and July 1, 2021. Eligible patients were age 18 to 55 and had no known prior infection with, or vaccination against, SARS-CoV-2. Patients with prior use of immunosuppressive or chemotherapeutic agents, or treatment with any anti-CD20 therapy other than ocrelizumab within 12 months of enrollment, were excluded. The Roche Elecsys anti-SARS-CoV-2 S immunoassay was performed prior to and 3-4 weeks post vaccination to evaluate the antibody response to SARS-CoV-2 spike IgG. The Adaptive Biotechnologies T-Detect COVID Test was performed to evaluate the adaptive T-cell immune response to SARS-CoV-2 in OCR-treated patients with no detectable antibodies. Data were analyzed using descriptive statistics, Fisher's exact test, and Wilcoxon rank sum. RESULTS: Forty-eight patients were enrolled in the study, 69% treated with ocrelizumab and 31% treated with natalizumab. Eighteen percent of ocrelizumab and 100% of natalizumab patients had a positive antibody response. In ocrelizumab-treated patients, there was no correlation between age, sex, BMI, total number of infusions, immunoglobulin G, CD19, or absolute lymphocyte count and antibody response. There was a trend suggesting that a longer interval between the last infusion and vaccination increased the likelihood of producing antibodies (P = 0.062). All ocrelizumab patients with negative antibody responses had positive T-cell responses. CONCLUSIONS: Treatment with ocrelizumab substantially impaired the humoral response to SAR-CoV-2 vaccination but did not impair T-cell responses. Further research is needed to determine if the T-cell response to SARS-CoV-2 vaccination is sufficient to prevent infection or reduce severity of COVID in patients who did not produce antibodies.


Subject(s)
COVID-19 , Multiple Sclerosis , Adolescent , Adult , Antibodies, Monoclonal, Humanized , Antibodies, Viral , COVID-19 Vaccines , Cohort Studies , Humans , Middle Aged , Multiple Sclerosis/drug therapy , Prospective Studies , SARS-CoV-2 , T-Lymphocytes , Vaccination , Young Adult
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