Longitudinal Assessment of 4-Year HFMSE Changes in SMA II and III Patients Treated With Nusinersen.

Background: The aim of this international retrospective study was to assess 4-year change using the Hammersmith Functional Motor Scale Expanded (HFMSE) in individuals with type II and III spinal muscular atrophy (SMA) treated with nusinersen and to establish predictors of HFMSE changes.

Methods: Individuals with type II or III SMA, and at least 4 years of nusinersen-only treatment were included. All were assessed using the HFMSE.

Uncovering a bias in estimated treatment effects on PIRA in multiple sclerosis clinical trials.

Background: Interest in progression independent of relapse activity (PIRA) as an endpoint in multiple sclerosis (MS) clinical trials is surging. However, established definitions of PIRA may produce biased treatment effect estimates in the presence of a treatment-induced relapse reduction.

Methods: We applied different definitions of PIRA to pooled data from the OPERA I/II clinical trials (clinicaltrials.

Personalized Treatment Response in Progressive MS: Can the Patient's Profile Influence the Outcome?

Background: Evidence from clinical trials providing average effects in populations is often used to forecast individualized patient outcomes similar to the trial patients. Multiple sclerosis (MS), known for notable heterogeneity in outcomes, makes the evaluation of potential heterogeneity of treatment effect (HTE) significant. Identifying factors that predict individual treatment response is crucial for optimizing patient care, and this study aimed to demonstrate the feasibility (proof of concept) of applying a statistical method to predict individual treatment response in MS trials.

Long-Term Effectiveness and Safety of Rituximab in Neuromyelitis Optica Spectrum Disorder: A 5-Year Observational Study.

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a severely disabling autoimmune disease that predominantly impacts the optic nerves and spinal cord. It is often linked to immunoglobulin G (IgG) antibodies targeting the aquaporin-4 water channel (AQP4-IgG). Rituximab, which depletes CD20-positive B cells, is effective in reducing the frequency of NMOSD relapses.

Effect of human papillomavirus infection on semen quality and assisted reproductive technology outcomes: a prospective observational cohort study.

Background: Human papillomavirus (HPV) adversely affects human reproduction. We aimed to evaluate the prevalence of HPV infection in men and its correlation with semen parameters and reproductive outcomes.

Methods: In this prospective observational cohort study, 384 semen samples were collected from 237 male partners of infertile couples.

Treating juvenile dermatomyositis to target: Paediatric Rheumatology European Society/Childhood Arthritis and Rheumatology Research Alliance-endorsed recommendations from an international task force.

Objectives: Despite the recent prognostic improvement, a sizeable proportion of patients with juvenile dermatomyositis (JDM) respond suboptimally to contemporary therapies. This study aimed to develop recommendations for treating JDM to target.

Methods: A Steering Committee formulated a set of provisional recommendations based on evidence derived from a systematic literature review and a retrospective chart review of patients.

Cut-Off Values Able to Identify Migraine Patients With Increased Pressure-Pain Sensitivity Independent of the Migraine Cycle Through a Single Assessment: A Secondary Analysis of a Multicentre, Cross-Sectional, Observational Study.

Aim: Identify values that could predict the presence of increased pressure-pain sensitivity independent of the migraine cycle through a single assessment.

Methods: This was a secondary analysis of a previous study in which 198 episodic and chronic migraine patients were assessed during all phases of the migraine cycle. Pressure pain threshold (PPT) was assessed over the temporalis, cervical spine, hand, and leg.

A data-driven model of disability progression in progressive multiple sclerosis.

This study applies the Gaussian process progression model, a Bayesian data-driven disease progression model, to analyse the evolution of primary progressive multiple sclerosis. Utilizing data from 1521 primary progressive multiple sclerosis participants collected within the International Progressive Multiple Sclerosis Alliance Project, the analysis includes 18 581 longitudinal time-points (average follow-up time: 28.2 months) of disability assessments including the expanded disability status scale, symbol digit modalities, timed 25-foot-walk, 9-hole-peg test and of MRI metrics such as T1 and T2 lesion volume and normalized brain volume.

Predictors for choosing doravirine-based versus INSTI-based regimen in ART-naïve and ART-experienced people with HIV in real-world setting: Data from the Icona cohort.

Rationale: Doravirine (DOR) is an attractive new option both for ART-naïve people with HIV (PWH) and those with suppressed HIV-RNA who seek treatment simplification. We used real-world data to examine the pattern of use of DOR-containing regimens in these settings.

Methods: All PWH enrolled in the Icona cohort after January 2020 who initiated a three-drug regimen (3-DR) with DOR or an integrase inhibitor (INSTI)-based regimen as first antiretroviral therapy (ART) or when switching ART, with HIV-RNA ≤50 copies/mL, were included.

Creating an automated tool for a consistent and repeatable evaluation of disability progression in clinical studies for multiple sclerosis.

Background: The lack of standardized disability progression evaluation in multiple sclerosis (MS) hinders reproducibility of clinical study results, due to heterogeneous and poorly reported criteria.

Objective: To demonstrate the impact of using different parameters when evaluating MS progression, and to introduce an automated tool for reproducible outcome computation.

Methods: Re-analyzing BRAVO clinical trial data (NCT00605215), we examined the fluctuations in computed treatment effect on confirmed disability progression (CDP) and progression independent of relapse activity (PIRA) when varying different parameters.

High NEDA and No PIRA in Natalizumab-Treated Patients With Pediatric-Onset Multiple Sclerosis.

Background And Objectives: Although pediatric-onset multiple sclerosis (POMS) is characterized by a more rapid accumulation of CNS inflammation than adult-onset MS (AOMS), the therapeutic algorithms applied in POMS are usually based on AOMS therapeutic outcomes. To define a high-efficacy treatment (HET)-based strategy to treat POMS, we designed an observational retrospective study aimed at evaluating the efficacy and safety of natalizumab (NTZ) in naïve POMS and AOMS.

Methods: Starting from 160 patients, we applied a 2:1 (adult:pediatric) matching on propensity scores and obtained 32 patients with NTZ-treated POMS and 64 with AOMS, estimated from a multivariable logistic regression model.

Hyper-reflective foci changes in RRMS under natalizumab therapy.

Introduction: Microglia (MG) is suggested to play an immunopathological role of in Multiple Sclerosis (MS). Since hyper-reflective foci (HRF) might mark MG activation, analysis by Optic Coherence Tomography (OCT) in MS patients under disease modifying therapies may help to clarify MS immunopathology as well as drug's mechanism of intrathecal action.

Objective: To analyze HRF in patients treated with Natalizumab (NTZ), a high efficacy therapy for MS.

Dimethyl fumarate preserves brainstem and cervical spinal cord integrity in radiologically isolated syndrome.

Background And Purpose: The first randomized placebo-controlled therapeutic trial in radiologically isolated syndrome (RIS), ARISE, demonstrated that treatment with dimethyl fumarate (DMF) delayed the onset of a first clinical event related to CNS demyelination and was associated with a significant reduction in new and/or newly enlarging T2-weighted hyperintense lesions. The purpose of this study was to explore the effect of DMF on volumetric measures, including whole brain, thalamic, and subcortical gray matter volumes, brainstem and upper cervical spine three-dimensional (3D) volumes, and brainstem and upper cervical spine surface characteristics.

Methods: Standardized 3T MRIs including 3D isotropic T1-weighted gradient echo images were acquired at baseline and end-of-study according to the ARISE study protocol.

Development and initial validation of parent and child versions of the Juvenile Arthritis Disease Activity Score.

Objective: To develop parent- and child-centred versions of the Juvenile Arthritis Disease Activity Score (JADAS) and to provide preliminary evidence of their validity.

Methods: Validation analyses were conducted on two large multinational datasets of patients with juvenile idiopathic arthritis (JIA) and included assessment of construct validity, internal consistency and structure, discriminative validity, responsiveness to change, and predictive validity.

Results: The parJADAS and patJADAS include four parent/patient-reported outcomes, each measured on a 0-10 scale: assessment of overall disease activity; rating of pain intensity; assessment of activity of joint disease; and duration of morning stiffness.

Race and ethnicity in multiple sclerosis phase 3 clinical trials: A systematic review.

Background: Distinctive differences in multiple sclerosis (MS) have been observed by race and ethnicity. We aim to (1) assess how often race and ethnicity were reported in clinical trials registered on , (2) evaluate whether the population was diverse enough, and (3) compare with publications.

Methods: We included phase 3 clinical trials registered with results on between 2007 and 2023.

The HyperPed-COVID international registry: Impact of age of onset, disease presentation and geographical distribution on the final outcome of MIS-C.

Objectives: The aim of the study was to establish an international multicenter registry to collect data on patients with Multisystem Inflammatory Syndrome in Children (MIS-C), in order to highlight a relationship between clinical presentation, age of onset and geographical distribution on the clinical outcome.

Study Design: Multicenter retrospective study involving different international societies for rare immunological disorders.1009 patients diagnosed with MIS-C between March and September 2022, from 48 centers and 22 countries were collected.

Determining minimal clinically important differences in the Hammersmith Functional Motor Scale Expanded for untreated spinal muscular atrophy patients: An international study.

Background And Purpose: Spinal muscular atrophy (SMA) is a rare and progressive neuromuscular disorder with varying severity levels. The aim of the study was to calculate minimal clinically important difference (MCID), minimal detectable change (MDC), and values for the Hammersmith Functional Motor Scale Expanded (HFMSE) in an untreated international SMA cohort.

Methods: The study employed two distinct methods.

Therapeutic lag: Is treatment effect delayed in progressive MS?

Background: Randomized clinical trials (RCTs) in progressive multiple sclerosis (MS) often revealed non-significant treatment effects on disability progression.

Objectives: To investigate whether the failure to detect a significant benefit from treatment may be motivated by a delay in treatment effect, possibly related to baseline characteristics.

Methods: We re-analyzed data from two RCTs testing interferon-beta and glatiramer-acetate versus placebo in progressive MS with no significant effect on EDSS progression.

Algorithm vs. clinical experience: controlled ovarian stimulations with follitropin-delta and individualised doses of follitropin-alpha/beta.

In the registrational trials, follitropin delta was compared with a fixed dose of 150 UI of follitropin alpha/beta, finding higher chances to reach a target response of 8-14 oocytes compared to controls. For this reason, follitropin delta is marketed as particularly useful in expected hyper-responder patients. The main outcome of this study is to report if comparable results are reached in a real-life scenario with follitropin alpha/beta personalized doses, based on patients' characteristics.