Infectious risk stratification in multiple sclerosis patients receiving immunotherapy (original) (raw)
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International journal of MS care, 2021
Background Patients with a compromised immune system are at risk for converting from latent tuberculosis infection (LTBI) to active tuberculosis (TB) infection. Multiple sclerosis (MS) therapies may put individuals with LTBI at higher risk of TB. Methods Patients at the Beth Israel Deaconess Medical Center MS Clinic were screened for TB as part of routine testing with the QuantiFERON-TB Gold In-Tube (QFT-GIT) assay (Cellestis Ltd) from 2013 to 2017. Patients were tested either before or during immunomodulatory therapy. Results Four of 222 patients (1.8%; 95% CI, 0.1%-3.6%) had positive QFT-GIT results; three patients had risk factors for TB, having emigrated from TB-endemic countries or worked in the health care industry. Twenty-eight of 222 patients (12.6%) had an indeterminate assay result, and 75.0% of these occurred in patients taking dimethyl fumarate. Fingolimod, natalizumab, or anti-CD20 treatments showed 0% to 7.7% indeterminate results. Conclusions The prevalence of LTBI wa...
Arquivos de Neuro-Psiquiatria
Background Multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) are the most common autoimmune diseases of the central nervous system (CNS). They present chronic relapsing courses that demand treatment with disease-modifying drugs (DMDs) to prevent inflammatory activity. Disease-modifying drugs lead to immunomodulation or immunosuppression through diverse mechanisms (e.g., shifting lymphocyte and cytokine profile, suppressing specific lymphocyte subpopulations). Thus, patients are more prone to infectious complications and associated worsening of disease. Objective To present feasible strategies for mitigating the infection risk of MS and NMOSD treated patients. Methods Targeted literature review concerning the management of infection risk with an emphasis on vaccination, therapy-specific measures, and particularities of the Brazilian endemic infectious diseases' scenario. Conclusion We propose a vaccination schedule, infectious screening routine, and prop...
Medicina
In this paper, we reported on four cases of severe pulmonary active tuberculosis in patients with multiple sclerosis (MS) undergoing interferon beta-1b (IFNβ-1b) therapy. Disease-modifying therapies (DMTs) in MS may increase the risk of developing active tuberculosis (TB) due to their impact on cellular immunity. Screening for latent infection with Mycobacterium tuberculosis (LTBI) should be performed, not only for the newer DMTs (alemtuzumab, ocrelizumab) but also for IFNβ-1b, alongside better supervision of these patients.
Current Neurology and Neuroscience Reports
Purpose of Review The newer, higher-efficacy disease-modifying therapies (DMTs) for multiple sclerosis (MS)-orals and monoclonals-have more profound immunomodulatory and immunosuppressive properties than the older, injectable therapies and require risk mitigation strategies to reduce the risk of serious infections. This review will provide a systematic framework for infectious risk mitigation strategies relevant to these therapies. Recent Findings We classify risk mitigation strategies according to the following framework: (1) screening and patient selection, (2) vaccinations, (3) antibiotic prophylaxis, (4) laboratory and MRI monitoring, (5) adjusting dose and frequency of DMT, and (6) behavioral modifications to limit the risk of infection. We systematically apply this framework to the infections for which risk mitigations are available: hepatitis B, herpetic infections, progressive multifocal leukoencephalopathy, and tuberculosis. We also discuss up-to-date recommendations regarding COVID-19 vaccinations for patients on DMTs. Summary We offer a practical, comprehensive, DMT-specific framework of derisking strategies designed to minimize the risk of infections associated with the newer MS therapies.
Risk of opportunistic infections in patients treated with alemtuzumab for multiple sclerosis
Expert Opinion on Drug Safety, 2018
Introduction: Alemtuzumab is a monoclonal anti CD-52 antibody recently approved for use in relapsing-remitting multiple sclerosis(MS). Given that the targeted antigen is primarily expressed on B and T lymphocytes, the administration of this biological drug is associated with rapid but protracted peripheral lymphopenia. Areas covered: The impact on infective risk of this immune impairment is still to be fully understood. In this review, we attempt to summarize all the available literature concerning opportunistic infections occurring in patients with MS receiving alemtuzumab. Infective adverse events were observed in more than 70% of patients in phase 2/3 RCTs, mainly of mild-to-moderate severity. Nevertheless, several post-marketing reports documented cases of serious, rare and unexpected infections. Expert Opinion: Predictive risk factors and prognostic features of opportunistic infections in this setting still need to be exactly assessed. At present, the only recommended preventive measures consist in anti-herpetic prophylaxis, Listeria-free diet, Tuberculosis prophylaxis and annual Papillomavirus screening. Given the non-negligible risk of unpredicted infective events, we advise physicians to take into account patients' history of infectious diseases and vaccine status and to consider supplementary prophylactic strategies, including screening for Toxoplasma gondii and viral hepatitis serostatus as well as pre-emptive approaches to avert CMV reactivation and Pneumocystosis.
JAMA Neurology, 2019
IMPORTANCE Although highly effective disease-modifying therapies for multiple sclerosis (MS) have been associated with an increased risk of infections vs injectable therapies interferon beta and glatiramer acetate (GA), the magnitude of potential risk increase is not well established in real-world populations. Even less is known about infection risk associated with rituximab, which is extensively used off-label to treat MS in Sweden. OBJECTIVE To examine the risk of serious infections associated with disease-modifying treatments for MS. DESIGN, SETTING, AND PARTICIPANTS This nationwide register-based cohort study was conducted in Sweden from January 1, 2011, to December 31, 2017. National registers with prospective data collection from the public health care system were used. All Swedish patients with relapsing-remitting MS whose data were recorded in the Swedish MS register as initiating treatment with rituximab, natalizumab, fingolimod, or interferon beta and GA and an age-matched and sex-matched general population comparator cohort were included. EXPOSURES Treatment with rituximab, natalizumab, fingolimod, and interferon beta and GA. MAIN OUTCOMES AND MEASURES Serious infections were defined as all infections resulting in hospitalization. Additional outcomes included outpatient treatment with antibiotic or herpes antiviral medications. Adjusted hazard ratios (HRs) were estimated in Cox regressions. RESULTS A total of 6421 patients (3260 taking rituximab, 1588 taking natalizumab, 1535 taking fingolimod, and 2217 taking interferon beta/GA) were included, plus a comparator cohort of 42 645 individuals. Among 6421 patients with 8600 treatment episodes, the mean (SD) age at treatment start ranged from 35.0 (10.1) years to 40.4 (10.6) years; 6186 patients were female. The crude rate of infections was higher in patients with MS taking interferon beta and GA than the general population (incidence rate, 8.9 [95% CI, 6.4-12.1] vs 5.2 [95% CI, 4.8-5.5] per 1000 person-years), and higher still in patients taking fingolimod (incidence rate, 14.3 [95% CI, 10.8-18.5] per 1000 person-years), natalizumab (incidence rate, 11.4 [95% CI, 8.3-15.3] per 1000 person-years), and rituximab (incidence rate, 19.7 [95% CI, 16.4-23.5] per 1000 person-years). After confounder adjustment, the rate remained significantly higher for rituximab (HR, 1.70 [95% CI, 1.11-2.61]) but not fingolimod (HR, 1.30 [95% CI, 0.84-2.03]) or natalizumab (HR, 1.12 [95% CI, 0.71-1.77]) compared with interferon beta and GA. In contrast, use of herpes antiviral drugs during rituximab treatment was similar to that of interferon beta and GA and lower than that of natalizumab (HR, 1.82 [1.34-2.46]) and fingolimod (HR, 1.71 [95% CI, 1.27-2.32]). CONCLUSIONS AND RELEVANCE Patients with MS are at a generally increased risk of infections, and this differs by treatment. The rate of infections was lowest with interferon beta and GA; among newer treatments, off-label use of rituximab was associated with the highest rate of serious infections. The different risk profiles should inform the risk-benefit assessments of these treatments.
Neuromyelitis Optica (NMO) with Abdominal Tuberculosis (TB)
Journal of the College of Physicians and Surgeons--Pakistan : JCPSP, 2015
Neuromyelitis Optica (NMO), previously regarded as a form of multiple sclerosis, is defined by Gault and Devic, as a retrobulbar neuritis or papillitis accompanied by acute myelitis and occasionally other neurological symptom or signs not restricted to the spinal cord or optic nerves. With the diagnosis of specific antibodies, probable role of humoral immunity supports its pathogenesis. Only a few cases of NMO have been reported in association with pulmonary tuberculosis (TB). Here we report a case of young girl with acute onset paraplegia diagnosed to have NMO, who later on during hospital stay developed ascites which cultured positive for Mycobacterium tuberculosis. This association of abdominal TB with NMO is under-reported in literature.
Prospective study on the relationship between infections and multiple sclerosis exacerbations
Brain, 2002
One of the characteristics of multiple sclerosis is the unpredictable occurrence of exacerbations and remissions. These¯uctuations in disease activity are related to alterations in (auto-)immune activity. Exacerbations lead to short-term morbidity, but may also in¯uence longterm disability. This longitudinal study in 73 patients with relapsing±remitting multiple sclerosis assessed the contribution of systemic infections to the natural course of exacerbations. In addition, we analysed whether infections lead to an increase in the number of gadoliniumenhancing lesions. A total of 167 infections and 145 exacerbations were observed during 6466 patient weeks. During a prede®ned at-risk period (ARP) of 2 weeks before until 5 weeks after the onset of a clinical infection (predominantly upper airway infections), there was an increased risk of exacerbations (rate ratio 2.1), which is in accordance with previous studies. Exacerbations with onset during the ARP led more frequently to sustained de®cit [increase of b1 Expanded Disability Status Scale (EDSS) point or b0.5 above EDSS 5.5 for >3 months] than exacerbations with onset outside the ARP, with a rate ratio of 3.8. Minor and major exacerbations were equally distributed between the ARP and non-ARP onset groups. ARP exacerbations were associated with signi®cantly higher plasma levels of the in¯ammatory marker soluble intracellular adhesion molecule 1 than non-ARP exacerbations, indicating relatively enhanced immune activation during ARP relapses. Three serial MRI scans were performed after the onset of an infection over a 6-week period. There was no difference in the number of gadolinium-enhancing lesions between the three time points. In conclusion, exacerbations in the context of a systemic infection lead to more sustained damage than other exacerbations. There is no indication that this effect occurs through enhanced opening of the blood± brain barrier.
European Journal of Neurology, 2010
Background: Although the benefit of treatment for relapsing-remitting multiple sclerosis (MS) is firmly established, whether interferon beta-1b (IFNB-1b) therapy is efficacious for neuromyelitis optica (NMO) has been debated. Methods: We reviewed the responses to IFNB-1b treatment in 18 patients with relapsing NMO and compared the results with those from 38 patients with relapsingremitting MS. We compared clinical characteristics, the annualized relapse rate (ARR) and the probability of being relapse free before and after IFNB-1b treatment in patients with NMO and MS. Results: The proportion of patients with more than 50% increase in the ARR after IFNB-1b treatment was much higher in NMO than in MS (P = 0.046). ARR was significantly lower in patients with MS after IFNB-1b administration than before (P = 0.015), but not in NMO. Kaplan-Meier and log-rank statistical analyses revealed that relapse-free rates were lower in NMO than MS after IFNB-1b treatment (P = 0.032). The analyses also showed lower relapse-free rates during the pre-IFNB-1b treatment period than the post-IFNB-1b treatment period in MS (P < 0.001), but not in NMO. Conclusion: IFNB-1b treatment does not appear to be effective for preventing relapse in NMO likely because of differences between the immune-pathogenesis of NMO and MS.