Simultaneous quantification of natural and inducible regulatory T-cell subsets during interferon-\u3b2 therapy of multiple sclerosis patients

The mechanisms underlying the therapeutic activity of interferon-\u3b2 in multiple sclerosis are still not completely understood. In the present study, we evaluated the short and long-term effects of interferon-\u3b2 treatment on different subsets of regulatory T cells in relapsing-remitting multiple sclerosis patients biologically responsive to treatment because of mixovirus resistance protein A inducibility

Extratemporal herpes encephalitis during natalizumab treatment: a case report

Herpes simplex virus encephalitis (HSE) is a rare but often fatal disease if left untreated. MRI typically shows the characteristic findings of medial temporal lobe and insular involvement, while diagnosis in confirmed by CSF PCR. In immunocompromised state, HSE may have atypical clinical and radiological features. We report a MS patient under natalizumab treatment with HSE, who presented with MRI lesions exclusively in the right parietal lobe. The patient was timely started on acyclovir resulting in marked improvement. A high index of suspicion for HSE should be maintained when a patient presents with fever and extratemporal lesions, even more in immunocompromised subjects

Escalation to natalizumab or switching among immunomodulators in relapsing multiple sclerosis

Objective: To evaluate whether an escalation approach was more effective in suppressing clinical and magnetic resonance imaging (MRI) activity than switching among immunomodulators in relapsing-remitting multiple sclerosis (RRMS) patients.Methods: In this post-marketing, prospective, observational study in two Italian multiple sclerosis (MS) centres, a total of 285 RRMS patients who failed a first-line treatment with interferon beta (IFNβ) or glatiramer acetate (GA) were considered. Patients were subdivided according to the strategy adopted after the failure (defined as the occurrence of ≥2 relapses or 1 relapse with residual disability): the switching (SWI) group, i.e. those switched among different IFNβ formulations, or from IFNβ to GA and vice versa; and the escalating (ESC) group, i.e. those escalated to natalizumab. Proportions of patients free from different types of disease activity (relapses, sustained disability progression, new active lesions on MRI, or a combination of them) were calculated at 12 and 24 months. Since patients were not randomized to treatment group, propensity score (PS)-adjusted Cox regression models were built to control for several potential confounders.Results: At 12 months there were no differences between the two groups in proportions of patients free from relapse, disability progression, MRI activity, and combined activity. After 24 months we observed greater proportions of patients in the ESC than SWI group free from relapse (p < 0.0001), disability progression (p = 0.0045), MRI activity (p = 0.0003), and combined activity (p < 0.0001). PS-adjusted models confirmed these findings, with hazard ratios ranging from 0.38 to 0.56 favours the ESC group.Conclusion: We suggest that an escalation to natalizumab is more effective than switching among immunomodulators in RRMS patients who failed a first-line treatment. © SAGE Publications 2012

Relapse-associated worsening in a real-life multiple sclerosis cohort: The role of age and pyramidal phenotype

Background: The overall disability in patients with relapsing-remitting multiple sclerosis (RRMS) is likely to be partly rather than entirely attributed to relapse. Materials and methods: We aimed to investigate the determinants of recovery from first relapse and relapse associated worsening (RAW) in RRMS patients from the Italian MS registry during a five-years epoch from the beginning of first-line disease modifying therapy. To determine recovery, the functional system score (FSS) was used to calculate the difference between the score on the date of maximum improvement and the score before the onset of relapse. Incomplete recovery was defined as a combination of partial (1 point in one FS), and poor recovery (two points in one FS or one point in two FSs or any other higher combination). RAW was indicated by a confirmed disability accumulation measured by the Expanded Disability status scale score confirmed 6 months after the first relapse. Results: A total of 767 patients had at least one relapse within 5-years of therapy. Of these patients, 57.8% experienced incomplete recovery. Age (OR= 1.02, 95% Confidence interval-CI 1.01-1.04; p = 0.007) and pyramidal phenotype were associated to incomplete recovery (OR= 2.1, 95% CI 1.41-3.14; p < 0.001). RAW was recorded in 179 (23.3%) patients. Age (OR= 1.02, 95% CI 1.01-1.04; p=0.029) and pyramidal phenotype (OR= 1.84, 95% CI 1.18-2.88; p = 0.007) were the strongest predictors in the multivariable model. Conclusions: Age and pyramidal phenotype were the strongest determinants of relapse-associated worsening in early disease epochs

Minimal evidence of disease activity (MEDA) in relapsing-remitting multiple sclerosis

Objective This study aimed to define the minimal evidence of disease activity (MEDA) during treatment that can be tolerated without exposing patients with relapsing-remitting multiple sclerosis at risk of long-term disability.Methods We retrospectively collected data of patients followed up to 10 years after starting interferon beta or glatiramer acetate. Survival analyses explored the association between the long-term risk of reaching an Expanded Disability Status Scale >= 6.0 and early clinical and MRI activity assessed after the first and second year of treatment. Early disease activity was classified by the so-called 'MAGNI MS score' (low: no relapses and <3 new T2 lesions; medium: no relapses and >= 3 new T2 lesions or 1 relapse and 0-2 new T2 lesions; high: 1 relapse and >= 3 new T2 lesions or >= 2 relapses) and the absence or presence of contrast-enhancing lesions (CELs).Results At follow-up, 148/1036 (14.3%) patients reached the outcome: 61/685 (8.9%) with low score (reference category), 57/241 (23.7%) with medium score (HR=1.94, p=0.002) and 30/110 (27.3%) with high score (HR=2.47, p<0.001) after the first year of treatment. In the low score subgroup, the risk was further reduced in the absence (49/607, 8.1%) than in the presence of CELs (12/78, 15.4%; HR=2.11, p=0.01). No evident disease activity and low score in the absence of CELs shared the same risk (p=0.54). Similar findings were obtained even after the second year of treatment.Conclusions Early marginal MRI activity of one to two new T2 lesions, in the absence of both relapses and CELs, is associated with a minor risk of future disability, thus representing a simple and valuable definition for MEDA

Identifying Relapses in Multiple Sclerosis Patients through Administrative Data: A Validation Study in the Lazio Region, Italy

Background: Relapse is frequently considered an outcome measure of disease activity in relapsing-remitting multiple sclerosis (MS). The objectives of this study were to identify relapse episodes in patients with MS in the Lazio region using health administrative databases and to evaluate the validity of the algorithm using patients enrolled at MS treatment centers. Methods: MS cases were identified in the period between January 1, 2006 and December 31, 2009 using data from regional Health Information Systems (HIS). An algorithm based on HIS was used to identify relapse episodes, and patients recruited at MS centers were used to validate the algorithm. Positive and negative predictive values (PPV, NPV) and the Cohen's kappa coefficient were calculated. Results: The overall MS population identified through HIS consisted of 6,094 patients, of whom 67.1% were female and the mean age was 41.5. Among the MS patients identified by the algorithm, 2,242 attended the centers and 3,852 did not. The PPV was 58.9%, the NPV was 76.3%, and the kappa was 0.36. Conclusions: The proposed algorithm based on health administrative databases does not seem to be able to reliably detect relapses; however, it may be a helpful tool to detect healthcare utilization, and therefore to identify the worsening condition of a patient's health

Induction Versus Escalation in Multiple Sclerosis: A 10-Year Real World Study

In this independent, multicenter, post-marketing study, we directly compare induction immunosuppression versus escalation strategies on the risk of reaching the disability milestone of Expanded Disability Status Scale (EDSS) >= 6.0 over 10 years in previously untreated patients with relapsing-remitting multiple sclerosis. We collected data of patients who started interferon beta (escalation) versus mitoxantrone or cyclophosphamide (induction) as initial treatment. Main eligibility criteria included an EDSS score <= 4.0 at treatment start and either >= 2 relapses or 1 disabling relapse with evidence of >= 1 gadolinium-enhancing lesion at magnetic resonance imaging scan in the pre-treatment year. Since patients were not randomized to treatment group, we performed a propensity score (PS)-based matching procedure to select individuals with homogeneous baseline characteristics. Comparisons were then conducted using Cox models stratified by matched pairs. Overall, 75 and 738 patients started with induction and escalation, respectively. Patients in the induction group were older and more disabled than those in the escalation group (p < 0.05). The PS-matching procedure retained 75 patients per group. In the re-sampled population, a lower proportion of patients reached the outcome after induction (21/75, 28.0%) than escalation (29/75, 38.7%) (hazard ratio = 0.48; p = 0.024). Considering the whole sample, serious adverse events occurred more frequently after induction (8/75, 10.7%) than escalation (18/738, 2.4%) (odds ratio = 3.36, p = 0.015). These findings suggest that, in patients with poor prognostic factors, induction was more effective than escalation in reducing the risk of reaching the disability milestone, albeit with a worse safety profile. Future studies are warranted to explore if newer induction agents may provide a more advantageous long-lasting risk:benefit profile