Background

Disease-modifying therapies (DMTs) for relapsing multiple sclerosis (RMS) modulate or deplete immune cells, including T and B cells. Healthcare professionals (HCPs) and patients consider many factors when selecting a DMT in a shared decision model, including efficacy, frequency/route of administration and safety. Patient understanding of mechanisms of action (MoA), and DMT effects on the dynamics and function of the immune system may be challenging to understand and further influenced by the COVID-19 pandemic, including risk interpretation and administration preferences.

Objectives

To assess the involvement of patients in MS treatment selection and the importance for patient understanding of MoA using a patient narrative approach, and to design a preliminary qualitative survey to inform future studies.

Methods

A preliminary qualitative survey was developed to explore factors most important to patients when considering DMTs, including patient understanding of immunological aspects of MS, MoAs, preferences regarding route of administration and provision of MS clinical information. Perspectives were sought from HCPs and patients on how this dialog has changed during the COVID-19 pandemic. The survey was distributed by email to 3 patients and 1 caregiver.

Results

Results are based on survey results and email correspondence from two adults with RMS, and an adolescent with pediatric MS and her caregiver. Overall, respondents felt they understood the general role of the immune system in MS and the role of DMTs but had poorer understanding of B and T cell functions and the impact of DMTs and their MoAs. Safety and efficacy were equally the most important variables when considering a new DMT. Face-to-face discussions between patients and HCPs were preferred to noninteractive materials; HCP authors (3 neurologists and 1 MS physician assistant) agreed that more face-to-face clinic time for dialog is needed. Patient independence was a key factor in preferences for methods of administration. Respondents reported an increase in MoA conversations in light of COVID-19.

Conclusions

While safety and efficacy are important in patients’ considerations of DMTs, there is a clear need to increase understanding of MoAs when starting or switching DMTs; immunological knowledge has become increasingly important during the COVID-19 pandemic. The preliminary qualitative survey can be used to inform future studies of what is needed to improve communication on DMT MoAs.

Background

Multiple sclerosis patients are treated with intravenous (IV) disease modifying treatments (DMTs). Infusion suite resources are thus vital components of MS patient care. Infusion suites may be dedicated to MS patients, or shared with patients with other neurological conditions, or other patients requiring infusion. Here, we describe a resource utilization model for the infusion suites of Charing Cross (UK), which serves patients with different neurological conditions.

Objectives

To maximize the clinical efficiency of the infusion suite based on three resource constraints: percentage of patients IV MS DMTs, number of infusion chairs, and number of nurses. Efficiency gains in the infusion suite may benefit both patients and the healthcare system.

Methods

ENTIMOS, a discrete event simulation (DES) model, was created using SIMUL8 based on qualitative information from infusion centers and populated with data specific to the Charing Cross hospital neurology infusion suite. Posology, administration information, and rates of immune related-reactions (IRRs) were applied from published data sources from both MS and non-MS DMTs of interest.

The infusion suite model assumes 75 MS and 21 non-MS patients weekly, including up to seven MS patients initiating IV treatment; is equipped with 12 infusion chairs and six beds; and is staffed with a total of six nurses. We simulated the effects of changing the three resource constraints described on the number of patients waiting for an appointment (queue size), the time for patients to get an appointment for their first or subsequent IV treatments (waiting times), and general resource utilization.

Results

Changing the number of chairs, moving a subset of patients from IV to any non-IV alternative treatments, moving patients between MS IV treatments, or changing the allocation of nurse resources may all have an impact on the queue size and waiting times. Once the changes are implemented in the model, existing resources optimised and the queue size reduced, the effective centre throughput can be increased.

Conclusions

ENTIMOS allows users to optimize their use of constrained resources in an infusion suite to improve patient experience and infusion suite efficiency.

Background

FLUENT investigated immune cell subset changes in the innate and adaptive immune systems during fingolimod therapy, and their associations with efficacy and safety outcomes.

Objectives

To report changes in immune cell profile, efficacy and safety of fingolimod 0.5 mg/day in adults with relapsing multiple sclerosis (RMS).

Methods

In FLUENT (NCT03257358), a prospective, 12 month, phase 4, multicenter, nonrandomized, open-label study, patients were stratified as fingolimod naive (Cohort 1) or previously treated with fingolimod 0.5 mg/day continuously for ≥2 years (Cohort 2). Primary outcome was change from Baseline to Month 12 in immune cell subsets. Secondary outcomes included Patient Determined Disease Steps (PDDS), anti-John Cunningham virus (anti-JCV) antibody status, serum neurofilament light chain (NfL) concentration, and adverse events (AEs) incidence. Data were analyzed from all patients completing Month 12 follow-up.

Results

165 patients enrolled in Cohort 1; 217 in Cohort 2. Proportionally more patients in Cohort 1 than Cohort 2 relapsed in the year before baseline. At Baseline, patients in Cohort 1 had proportionally more naive and central memory CD4+ and CD8+ T cells and memory B cells, and proportionally fewer effector memory CD4+ and CD8+ T cells and regulatory B cells, than those in Cohort 2. At Month 12, between-cohort differences in the proportions of these lymphocyte types/subtypes were much reduced or negligible. Levels were essentially unchanged in Cohort 2, indicating reductions in naive T cells and increases in effector memory T cells and regulatory B cells in Cohort 1. Mean baseline PDDS scores were low (Cohort 1, 1.7; Cohort 2, 1.8), and changed little by Month 12. Median change from Baseline in anti-JCV antibody index was small in both cohorts. Proportions of patients with positive JCV serology remained stable at Month 12 (61% and 67% in Cohorts 1 and 2 vs 57% and 65% at Baseline). Mean serum NfL level was higher in Cohort 1 than Cohort 2 at Baseline (12.2 vs 9.6 pg/mL); levels were similar at Month 12 (8.7 vs 9.8 pg/mL), having reduced substantially in Cohort 1. Proportionally more patients in Cohort 1 than in Cohort 2 had treatment-emergent AEs (54.6% vs 44.2%), and discontinued study treatment (12.3% vs 5.5%); 5.5% of patients in each cohort reported serious AEs.

Conclusions

These data expand our knowledge of changes in immune cell profiles over time in patients with RMS treated with fingolimod in the short or long term.

Background

Depletion of B cells in patients with relapsing multiple sclerosis (RMS) using anti-CD20 monoclonal antibodies (mAbs) reduces annualized relapse rates and inflammatory lesion activity on magnetic resonance imaging, and delays time to confirmed disability worsening. Anti-CD20 mAbs ocrelizumab and rituximab are administered by intravenous infusion in clinic; ofatumumab is administered subcutaneously with a pre-filled syringe or autoinjector (AI) pen, facilitating self-administration. No outcome data exist relating to transition of patients treated with ocrelizumab or rituximab to ofatumumab.

Objectives

OLIKOS is a 12 month, prospective, single-arm, multicenter phase 3b study that will explore maintained efficacy of ofatumumab in patients with RMS who transition from intravenous anti-CD20 mAb therapy.

Methods

About 100 adults with RMS will be enrolled at 10-20 centers in the USA. Eligible patients will have been previously treated with 2-5 consecutive courses of intravenous ocrelizumab or rituximab (other anti-CD20 mAbs are excluded), with last dose 4-9 months before OLIKOS baseline. Other inclusion criteria are Expanded Disability Status Scale score 5.5 or lower at screening and CD19 B cells depleted to below 1% at baseline. Patients with suboptimal response to anti-CD20 therapy in the previous 6 months (relapse, ≥2 active gadolinium-enhancing [Gd+] lesions, any new/enlarging T2 lesions, clinical worsening), or who discontinued anti-CD20 therapy because of severe infusion-related reactions or recurrent infections, or with progressive disease, will be excluded. All participants will receive subcutaneous ofatumumab 20 mg administered by AI pen on Days 1, 7 and 14, then monthly in Months 1-12. The primary endpoint will be no change or a reduction in Gd+ lesion count at Month 12. Secondary endpoints will be participant retention and changes in immune biomarkers, treatment satisfaction, safety and tolerability at Months 6 and 12. There will be a 6 month interim analysis.

Results

The detailed study design will be presented. OLIKOS will complement the ofatumumab phase 3 program in RMS by generating maintained efficacy, retention and satisfaction data based on monthly subcutaneous drug delivery with the AI pen in patients previously treated with ocrelizumab or rituximab.

Conclusions

OLIKOS will provide important data on the maintained efficacy of ofatumumab in patients with RMS transitioning from intravenous anti-CD20 therapies.