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

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

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

Proportion of patients class switching from first to second IFNβ preparation.

<p>Proportion of patients class switching from first to second IFNβ preparation.</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 subsequent treatment discontinuation.

<p>Abbreviations: n: number, HR: Hazard Ratio, CI: Confidence Interval, IFN: Interferon, IM: intramuscular, SC: Subcutaneous, GA: Glatiramer Acetate, NAT: Natalizumab, EDSS: Expanded disability status scale.</p><p>Treatment initiations n = 599.</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 = 0.2270.</p>*<p>No EDSS score available at treatment start.</p

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

<p>A: Treatment discontinuation by DMT. This figure demonstrates that patients prescribed Natalizumab as a subsequent DMT discontinue treatment at a significantly slower rate than those prescribed Glatiramer Acetate or any of the IFNβ preparations (adjusted Cox Proportional Hazards Regression, p = 0.000). B: Treatment discontinuation by EDSS. This figure demonstrates that patients with EDSS 1–2.5 (p = 0.046), EDSS 3–5.5 (p = 0.013) and EDSS ≥6 (p = 0.008) discontinue treatment at a significantly greater rate than those with EDSS 0 (adjusted Cox Proportional Hazards Regression).</p

Baseline Patient Characteristics at subsequent 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