Use Of Immunomodulatory Therapies Research Articles

Therapy of multiple sclerosis in children and adolescents

Background Paediatric multiple sclerosis accounts for up to 10% of all MS cases. The initial course of the disease is relapsing-remitting in most children, with a relapse rate generally higher than that observed in adult patients. There is published experience on the use of first-line disease modifying therapies in children with MS. However, about 1/3 of paediatric MS cases do not respond to IFN-β or glatiramer acetate and continue to develop relapses and disease progression. These patients could be proposed to a second-line treatment. Methods A comprehensive review of the published literature related to pharmacologic treatment of MS in adults and paediatric patients was performed. The recent literature has been extracted for new evidence from controlled trials in adult patients, and open treatment studies and reported expert opinion in paediatric patients. Results No disease modifying drug has been approved for the treatment of children and adolescents with MS, although the currently available first-line therapies for adults seem to be safe and well tolerated in this population. Further studies are required to assess the safety and efficacy of second-line treatments in children with MS. Conclusion The present article constitutes an update of the existing publications regarding treatment of acute events of CNS demyelination in children and adolescents as well as considerations for the use of immunomodulatory therapies.

M1144 Factors Influencing the Use of Immunomodulatory Therapies During the Early Course of Disease in Patients with IBD - Results of a Population-Based Cohort

M1144 Factors Influencing the Use of Immunomodulatory Therapies During the Early Course of Disease in Patients with IBD - Results of a Population-Based Cohort

Fulminant hepatic failure complicating visceral leishmaniasis in an apparently immunocompetent child

Fulminant hepatic failure (FHF) is an unusual complication of visceralleishmaniasis (VL). Here, we present a 1.5-yr-old girl with VL developing rapidly progressive fatal FHF. In absence of established guidelines, additional use of immunomodulatory therapies has been discussed in reference to available information.

Myasthenia gravis: a long term follow-up study of Swedish patients with specific reference to thymic histology

Background:Myasthenia gravis (MG) is an autoimmune disorder of neuromuscular transmission. The majority of patients show abnormal thymic histology.Setting:The study was performed at the Myasthenia Gravis Centre, Karolinska University Hospital, and...

Severe recurrent myelitis in patients with hepatitis C virus infection

<h3>Background and importance</h3> Alemtuzumab is a humanised monoclonal antibody that selectively targets CD52, indicated in adult patients with relapsing–remitting multiple sclerosis (RRMS). <h3>Aim and objectives</h3> To assess the effectiveness and safety of alemtuzumab for RRMS in the clinical setting. <h3>Material and methods</h3> A retrospective observational study of all patients with RRMS treated with at least one course of alemtuzumab from July 2016 to March 2019 was carried out. The drug was administered by intravenous infusion on 5 consecutive days at baseline and on 3 consecutive days 12 months later. All patients received prophylaxis with methylprednisolone, antihistamines, antipyretics and acyclovir. Alemtuzumab was started in adults with active disease, defined by clinical or imaging features despite the use of immunomodulating therapies, or having a fast and aggressive course. The variables studied were sex, age, time from diagnosis, expanded disability status scale (EDSS), previous treatment, number of cycles, adverse events (AE) and number of relapses post-treatment (NRPT). Data were collected from medical records and the electronic prescription programme. Effectiveness was evaluated in terms of NRPT with alemtuzumab. Safety was assessed by reported treatment of AE. <h3>Results</h3> Eleven patients, 63.6% women, mean age 38 (24–54) years, were included. Median time from RRMS diagnosis was 10 (4–20) years and mean baseline EDSS was 3.5 (2–5.5). Patients were previously treated with a median of 3 (2–4) drugs: interferon beta-1a (IFNβ-1a) intramuscularly (45.5%), IFNβ-1a subcutaneously (27.3%), glatiramer acetate (27.3%), natalizumab (90.9%), fingolimod (27.3%) and dimethyl fumarate (18.2%). Seven patients completed two courses of alemtuzumab, and the second course is pending in three patients. One administration was suspended due to an infusion related reaction (IRR), requiring intensive care. The mean relapse rate was 0.36 (0–2). All patients experienced IRRs: lymphopenia (63.6%) and skin disorders (72.7%). Most were mild and limited in time, except for one patient with skin rash, pruritus and oedema, requiring discontinuation of treatment. Other AE were urinary tract infection (18.2%) and herpes zoster infections (9.1%). <h3>Conclusion and relevance</h3> According to our results, alemtuzumab was effective in clinical practice due to a low relapse rate. However, further studies with a larger number of patients are needed to confirm these results. IRRs were frequent. Nevertheless, AE were mild and well tolerated. <h3>References and/or acknowledgements</h3> None. No conflict of interest.

Increased Tumor Infiltrating FOXP3+ Regulatory T-Cells Are Associated with Improved Survival in Classical Hodgkin Lymphoma.

Background: Regulatory T-cells (Tregs), a CD4+, CD25+, FOXP3+ subset, appear to modulate the tumor microenvironment in lymphoma. Using FOXP3 expression as a marker of Tregs, single series have suggested that higher numbers of tumor infiltrating FOXP3+ cells are associated with improved survival in both follicular lymphoma and classical Hodgkin lymphoma (cHL). However, neither of these findings has been confirmed by separate studies and, in fact, contradictory data exists. We sought to evaluate potential correlations between the number of FOXP3+ cells in the tumor microenvironment and patient outcome.Methods: 98 previously untreated cHL patients, biopsied and treated with curative intent at the Cleveland Clinic, were studied. FOXP3 was assessed by immunohistochemistry (Abcam) and quantitated as the number of positive cells per high power field (hpf), averaged over 5 fields. Histology was evaluated and medical records were reviewed for clinical features (including gender, age, stage, B symptoms, bulk, number of sites and IPS), lymphoma progression and death.Results: The mean number of FOXP3+ cells (±standard deviation) was 41.7 ± 33.9 cells/hpf, and the median number was 36.4 cells/hpf (range 0–152.0 cells/hpf). Higher numbers of FOXP3+ T-cells were associated with age<45 (P=.02), stage I–II (P=.01), and IPS≤2 (P=.06) [Wilcoxon rank sum test]. 28 of the 98 patients (29%) have progressed and/or died and 20 (20%) have died. The estimated 5-year failure free survival (FFS) and overall survival (OS) are 76%±4% and 86%±4%, respectively. 70 patients remain alive with no evidence of disease at a median follow-up of 8.6 years (range 0.9–19.9 years). Recursive partitioning demonstrated an optimal cutoff of 25 FOXP3+ cells/hpf for analysis of outcome. Overall, 43 patients (44%) had a mean of <25.0 FOXP3+ cells/hpf and 55 (56%) had 25.0 or more. In univariate analysis, higher numbers of FOXP3+ T-cells in the tumor microenvironment were associated with better FFS; estimated 5-year FFS was 91% ± 4% for patients with >25.0 FOXP3+ cells/hpf compared to 81% ± 6% for patients with <25.0 (P=.05, generalized Wilcoxon test). There was also a trend towards improved OS (P=.10). In multivariate analysis, the number of FOXP3+ T-cells remained an independent predictor, even after adjusting for age, stage, and IPS ( P<.05). Kaplan-Meier curves for FFS and OS stratified by FOXP3+ “status” are shown in Figures 1 and 2.Conclusion: FOXP3+ T cells are a favorable prognostic marker in cHL and reflect the importance of the immune response thus providing rationale for the use of immunomodulatory therapies in these patients. [Display omitted] [Display omitted]

Immunomodulatory treatment of multiple sclerosis in Denmark: a prospective nationwide survey

Objective: The aim of the present study was to provide data on the use of immunomodulatory therapies in a population comprising all treated patients with relapsing-remitting multiple sclerosis (RRMS) in Denmark. Patients and methods: From the introduction of immunomodulatory therapy in Denmark in 1996 through 2003, all patients that started immunomodulatory therapy were followed prospectively with neurological examination and standard laboratory tests every six months, and clinical data were reported to the MS Treatment Register, including relapses, Expanded Disability Status Scale scores and side effects. Results: From 1996 through 2003 in all 2393 patients had started immunomodulatory therapy for RRMS, of whom 1252 (52.3%) were still on therapy with the same product at follow-up on 1 January 2005, whereas 1141 patients had discontinued or changed immunomodulatory therapy. Multiple Cox regression analysis of the risk of suffering a relapse showed a hazard ratio of 1.48 in patients with three or more relapses in the 24 months prior to onset compared with patients with two relapses or less; the hazard ratio was 0.84 in patients with age ≥ 38 years at treatment start compared with patients of age <38, and 1.17 for females compared with males. For disease progression the hazard ratio was 1.24 for age = 38 years compared with age ≥ 37 years. Significant differences were observed in the hazard ratios between the different preparations, probably due to selection bias. Conclusion: The response to immunomodulatory therapy can be predicted to some extent from demographic variables. Differences between preparations can mainly be ascribed to selection bias, and open studies are not suited for comparison of efficacy between different preparations.

Maintenance infliximab therapy in patients with crohn’s disease: how long, how much, how frequent?

Maintenance infliximab therapy in patients with crohn’s disease: how long, how much, how frequent?

Influence of Infant Feeding Method on Postpartum Relapse of Mothers With MS

In an effort to determine relapse rates in breast-feeding and non—breast-feeding mothers with multiple sclerosis (MS) as well as differences in symptom prevalence between relapsing and non-relapsing mothers, weekly diaries through the first six postpartum months were kept by mothers to record the frequency and percentages of infant feeding by breast or formula and health problems that the mothers experienced. Of 140 mothers who breast-fed their infants, 35 (25%) experienced at least one neurologist-confirmed MS relapse during the first six months and 47 (33.6%) during the 12-month period; for non—breast-feeding mothers, 18 (51.4%) experienced relapse by six months and 22 (61.1%) by 12 months. MS relapse during pregnancy predicted increased relapse during the first three postpartum months while an increased percentage of infant feedings by breast predicted decreased relapse. Relapse the year before pregnancy and during pregnancy predicted increased relapse during the four- to six-month postpartum period. Length of time on immunomodulating therapy since delivery predicted increased relapse at seven to nine months. MS relapse during pregnancy predicted increased relapse at the 10- to 12- month period. For non—breast-feeding mothers none of the predictors of relapse were significant for the three-month period except use of immunomodulating therapy during the four- to six-month period when such use was associated with increased relapse. Relapsing compared with non-relapsing mothers reported significantly more MS-related symptoms during the three-month postpartum period. Decreased relapse rates during the first three months following delivery among breast-feeding mothers compared with non—breast-feeding mothers have implications for encouraging women with MS who wish to breast-feed their infants to do so, particularly if their pregnancy was free of relapse. Women with MS are also encouraged to postpone the initiation of immunomodulating therapy until three months following delivery or when breast-feeding is discontinued. (Int J MS Care. 2002; 4:183–191)

Stiff-Person Syndrome: Autoimmunity and the Central Nervous System

Stiff-person syndrome (SPS) is a rare disease of severe progressive muscle stiffness in the spine and lower extremities with superimposed muscle spasms triggered by external stimuli. Patients with SPS are often referred for psychiatric evaluation and the psychiatrist may be the first to diagnosis SPS. Psychosocial stressors often precede the first manifestations of the disease; depression, anxiety, and alcohol abuse are comorbid illnesses. The identification of an association with antibodies to glutamic acid decarboxylase (GAD) was invaluable for definitively establishing a pathological basis for the disease; antibodies to amphiphysin and gephyrin are also found in cases of SPS but at much lower frequencies. Whether the antibodies inhibit GAD activity in vivo, target GAD-expressing neurons for immune-mediated destruction, are part of a wider immune process, or are merely a marker for destruction of GAD-expressing neurons by an independent neurodegenerative process is not yet clear. Both electromyography and the detection of GAD antibodies are useful in establishing a diagnosis of SPS. Treatment of SPS includes the use of immunomodulating therapies (plasmapheresis and intravenous immunoglobulins) and symptomatic treatment with benzodiazepines and baclofen. The use of tricyclic antidepressants and rapid withdrawal from therapy should be avoided.

Therapeutic Apheresis in Multiple Sclerosis and Other Central Nervous System Disorders

Although the cause of multiple sclerosis (MS) remains unknown, the recent advances in research and the use of immunomodulating therapies have revolutionalized the way this disease is now approached. Apheresis is but one of the various immunomodulating therapies successfully used in MS. Pilot and double-blind randomized controlled studies, long-term follow-up studies, and the possible mechanism of action of therapeutic apheresis in MS are discussed. Based on our current knowledge, as well as on the available published data, it is concluded that apheresis is an effective therapy in severely progressive MS (both acute and chronic) when conventional therapies have failed.

How to investigate and manage the child with suspected acute encephalitis

The major advances in the diagnosis of acute encephalitis have been in the use of newer microbiological techniques (especially PCR) and in the use neuroimaging, particularly MRI. In every case it should be possible to provide optimum supportive treatment, although this will often require admission to an intensive care unit. Specific remedies against known or suspected infectious agents causing encephalitis are still few, and perhaps this is an area in which further progress could be made. There is also the potential for exploring the use of immunomodulating therapies in the future particularly in those encephalitides which are primarily immunologically mediated. The major advances in the diagnosis of acute encephalitis have been in the use of newer microbiological techniques (especially PCR) and in the use neuroimaging, particularly MRI. In every case it should be possible to provide optimum supportive treatment, although this will often require admission to an intensive care unit. Specific remedies against known or suspected infectious agents causing encephalitis are still few, and perhaps this is an area in which further progress could be made. There is also the potential for exploring the use of immunomodulating therapies in the future particularly in those encephalitides which are primarily immunologically mediated.