The Australian multiple sclerosis (MS) immunotherapy study: A prospective, multicentre study of drug utilisation using the MSBase platform

To prospectively characterise treatment persistence and predictors of treatment discontinuation in an Australian relapsing-remitting multiple sclerosis (RRMS) population. Tertiary MS treatment centres participating in the MSBase registry prospectively assessed treatment utilisation, persistence, predictors of treatment discontinuation and switch rates. Multivariable survival analyses were used to compare treatment persistence between drugs and to identify predictors of treatment discontinuation. 1113 RRMS patients were studied. Patients persisted on their first disease-modifying therapy (DMT) for a median of 2.5 years. Treatment persistence on GA was shorter than on all IFNβ products (p<0.03). Younger age at treatment initiation and higher EDSS were predictive of DMT discontinuation. Patients persisted on subsequent DMTs, for 2.3 years. Patients receiving natalizumab (NAT) as a subsequent DMT persisted longer on treatment than those on IFNβ or GA (p<0.000). The primary reason for treatment discontinuation for any drug class was poor tolerability. Annualised switch or cessation rates were 9.5–12.5% for individual IFNβ products, 11.6% for GA and 4.4% for NAT. This multicentre MS cohort study is the first to directly compare treatment persistence on IFNβ and GA to NAT. We report that treatment persistence in our Australian RRMS population is short, although patients receiving IFNβ as a first DMT persisted longer on treatment than those on GA. Additionally, patients receiving NAT as a subsequent DMT were more likely to persist on treatment than those switched to IFNβ or GA. EDSS and age at DMT initiation were predictive of DMT discontinuation. Treatment intolerance was the principal reason for treatment cessation

Persistence on therapy and propensity matched outcome comparison of two subcutaneous interferon beta 1a dosages for multiple sclerosis

To compare treatment persistence between two dosages of interferon β-1a in a large observational multiple sclerosis registry and assess disease outcomes of first line MS treatment at these dosages using propensity scoring to adjust for baseline imbalance in disease characteristics. Treatment discontinuations were evaluated in all patients within the MSBase registry who commenced interferon β-1a SC thrice weekly (n = 4678). Furthermore, we assessed 2-year clinical outcomes in 1220 patients treated with interferon β-1a in either dosage (22 µg or 44 µg) as their first disease modifying agent, matched on propensity score calculated from pre-treatment demographic and clinical variables. A subgroup analysis was performed on 456 matched patients who also had baseline MRI variables recorded. Overall, 4054 treatment discontinuations were recorded in 3059 patients. The patients receiving the lower interferon dosage were more likely to discontinue treatment than those with the higher dosage (25% vs. 20% annual probability of discontinuation, respectively). This was seen in discontinuations with reasons recorded as “lack of efficacy” (3.3% vs. 1.7%), “scheduled stop” (2.2% vs. 1.3%) or without the reason recorded (16.7% vs. 13.3% annual discontinuation rate, 22 µg vs. 44 µg dosage, respectively). Propensity score was determined by treating centre and disability (score without MRI parameters) or centre, sex and number of contrast-enhancing lesions (score including MRI parameters). No differences in clinical outcomes at two years (relapse rate, time relapse-free and disability) were observed between the matched patients treated with either of the interferon dosages. Treatment discontinuations were more common in interferon β-1a 22 µg SC thrice weekly. However, 2-year clinical outcomes did not differ between patients receiving the different dosages, thus replicating in a registry dataset derived from “real-world” database the results of the pivotal randomised trial. Propensity score matching effectively minimised baseline covariate imbalance between two directly compared sub-populations from a large observational registry

First-year treatment response predicts the following 5-year disease course in patients with relapsing-remitting multiple sclerosis

Predicting long-term prognosis and choosing the appropriate therapeutic approach in patients with Multiple Sclerosis (MS) at the time of diagnosis is crucial in view of a personalized medicine. We investigated the impact of early therapeutic response on the 5-year prognosis of patients with relapsing-remitting MS (RRMS). We recruited patients from MSBase Registry covering the period between 1996 and 2022. All patients were diagnosed with RRMS and actively followed-up for at least 5 years to explore the following outcomes: clinical relapses, confirmed disability worsening (CDW) and improvement (CDI), EDSS 3.0, EDSS 6.0, conversion to secondary progressive MS (SPMS), new MRI lesions, Progression Independent of Relapse Activity (PIRA). Predictors included demographic, clinical and radiological data, and sub-optimal response (SR) within the first year of treatment. Female sex (HR 1.27; 95 ​% CI 1.16–1.40) and EDSS at baseline (HR 1.19; 95 ​% CI 1.15–1.24) were independent risk factors for the occurrence of relapses during the first 5 years after diagnosis, while high-efficacy treatment (HR 0.78; 95 ​% CI 0.67–0.91) and age at diagnosis (HR 0.83; 95 ​% CI 0.79–0.86) significantly reduced the risk. SR predicted clinical relapses (HR ​= ​3.84; 95 ​% CI 3.51–4.19), CDW (HR ​= ​1.74; 95 ​% CI 1.56–1.93), EDSS 3.0 (HR ​= ​3.01; 95 ​% CI 2.58–3.51), EDSS 6.0 (HR ​= ​1.77; 95 ​% CI 1.43–2.20) and new brain (HR ​= ​2.33; 95 ​% CI 2.04–2.66) and spinal (HR 1.65; 95 ​% CI 1.29–2.09) MRI lesions. This study highlights the importance of selecting the appropriate DMT for each patient soon after MS diagnosis, also providing clinicians with a practical tool able to calculate personalized risk estimates for different outcomes

Baseline Patient Characteristics at first treatment initiation.

<p>Abbreviations: n, number; y, years; SD, standard deviation; IQR, interquartile range; EDSS, Expanded Disability Status Scale.</p>α<p>Pearson χ² test.</p>β<p>One-way ANOVA with Bonferroni’s post hoc test.</p>γ<p>Kruskal-Wallis rank sum test.</p

Categorical reasons for treatment discontinuation for all treatment commencements.

<p>Abbreviations: n, number.</p>α<p>Pearson χ² test.</p

Kaplan-Meier survival estimates for treatment discontinuation (First DMT).

<p>A: Treatment discontinuation by DMT. This figure demonstrates that patients prescribed Glatiramer Acetate as a first DMT discontinue treatment at a significantly greater rate than those prescribed any of the IFNβ preparations (adjusted Cox Proportional Hazards Regression, p<0.03). B: Treatment discontinuation by EDSS. This figure demonstrates that patients with an EDSS of 3–5.5 discontinue the use of a first DMT at a greater rate than those with an EDSS of 0 (adjusted Cox Proportional Hazards Regression, p = 0.08).</p

Predictors of first treatment discontinuation.

<p>Abbreviations: n: number, HR: Hazard Ratio, CI: Confidence Interval, IFN: Interferon, IM: intramuscular, SC: Subcutaneous, GA: Glatiramer Acetate, EDSS: Expanded Disability Status Scale.</p><p>Treatment initiations n = 760 excluding Natalizumab (n = 11).</p>α<p>Cox Proportional Hazards Regression.</p><p>Multivariable Cox Proportional Hazards model was adjusted for sex, disease duration, age at treatment start, treatment and EDSS.</p><p># Proportional hazards test: p = 0.3747.</p>*<p>No EDSS score available at the time of treatment start.</p