Background

Natalizumab and fingolimod are indicated in the EU for patients with rapidly evolving severe relapsing-remitting multiple sclerosis (RES RRMS; ≥2 relapses in 1 year and ≥1 gadolinium-enhancing lesions or increased T2 lesion numbers on MRI) or highly active RRMS. Patients with RRMS may also receive first-line therapies (interferon beta, glatiramer acetate, dimethyl fumarate, or teriflunomide; collectively BRACETD). Effectiveness comparisons of therapies in patients with RES RRMS are lacking.

Objectives

To compare the clinical effectiveness of natalizumab, fingolimod, and BRACETD in patients with RES RRMS in real-world settings.

Methods

Data from the MSBase registry as of August 2019 were used. Adults with RRMS, ≥2 relapses in the past 12 months, and available Expanded Disability Status Scale scores at baseline (BL) and on therapy were included. At index date, patients were treatment naive or had switched from BRACETD to natalizumab, fingolimod, or another BRACETD. Patients were propensity score matched 1:1:1 based on BL demographic and clinical variables. Annualized relapse rates (ARRs) were compared using a generalised estimating equation Poisson regression model. Other outcomes (time to first relapse, 6-month confirmed disability worsening [CDW], and 6-month confirmed disability improvement [CDI]) were analysed using Cox marginal regression models.

Results

Matched treatment groups included 721 triplets of patients with mean follow-up of approximately 3 years. In each group, 23.3–23.9% of patients were treatment naïve. ARR (95% CI) was lowest with natalizumab (0.18 [0.17–0.20]) followed by fingolimod (0.29 [0.26–0.31]) and BRACETD (0.39 [0.37–0.42]; P<0.001 for all comparisons); rate ratio (95% CI) vs BRACETD was 0.46 (0.42–0.53) for natalizumab and 0.72 (0.65–0.80) for fingolimod. Risk of first relapse was lower with natalizumab vs fingolimod (hazard ratio [HR] [95% CI], 0.63 [0.53–0.74]) or BRACETD (0.41 [0.36–0.48]; P<0.001 for both) and with fingolimod vs BRACETD (0.66 [0.57–0.76]; P<0.001). No differences in CDW were observed. CDI was more likely with natalizumab than with fingolimod (HR [95% CI], 1.25 [1.01–1.55]; P=0.047) or BRACETD (1.46 [1.16–1.85]; P=0.002). CDI was not significantly different between fingolimod and BRACETD (HR [95% CI], 1.17 [0.91–1.50]; P=0.209).

Conclusions

In this large cohort of patients with RES RRMS treated in real-world settings, natalizumab was more effective than fingolimod or BRACETD at reducing relapses. Natalizumab patients were also 25% and 46% more likely to exhibit CDI than fingolimod and BRACETD patients, respectively.

This study was supported by Biogen International (Zug, Switzerland).

Background

Cladribine tablets are approved for treatment of multiple sclerosis (MS) in many jurisdictions. Real-world outcomes data is very limited.

Objectives

We analysed the cladribine treatment experience in the MSBase registry. We described baseline characteristics, treatment pathways, and relapse and discontinuation outcomes in patients with ≥6 months follow-up data from cladribine initiation.

Methods

We performed a secondary data analysis using MSBase Registry data of patients with a confirmed diagnosis of MS and newly treated with cladribine tablets after regulatory approval. Descriptive statistics were used to analyze baseline patient characteristics recorded within 3 months prior to cladribine tablets initiation, including demographics, disease course and duration, prior disease modifying drugs (DMD), and Expanded Disability Status Scale (EDSS).

Results

As of the 4th June 2020, MSBase included 660 patients treated with cladribine from 9 countries, mainly from Australia and Europe. A total of 576 met all inclusion criteria. These included 496 relapsing-remitting MS (RRMS) patients. In these, median age at cladribine tablets start was 45 years and median disease duration since clinically isolated syndrome was 12.6 years. Median EDSS at cladribine tablets start was 2.5. Around 13% of all RRMS patients initiated cladribine tablets as first line therapy. Of all RRMS patients switching to cladribine tablets with a treatment gap of <6 months, the most common immediate prior DMDs were fingolimod (17%), followed by natalizumab, teriflunomide and dimethylfumarate (all appx. 10%). Total follow-up time was 340 patient-years. Annualised relapse rate (ARR) on cladribine tablets was 0.12 (95%CI 0.09-0.17), compared to a pre-cladribine ARR of 0.38. Treatment persistence was 95% after 12 months (95%CI 91-98%), and 92% after 24 months (95%CI 87-96%).

Conclusions

This study characterizes RRMS patients treated with cladribine tablets in a real-world clinic setting. First-line use was uncommon. ARR was low, consistent with clinical trial data, and early discontinuations were very rare.

Background

Ocrelizumab (OCR) is a humanised anti-CD20⁺ monoclonal antibody approved for the treatment of primary progressive multiple sclerosis (PPMS), and relapsing forms of MS, including both relapsing-remitting (RRMS) and secondary progressive MS (SPMS) with relapses.

Objectives

In a real-world setting, to describe 1) baseline characteristics of patients with MS treated with OCR, 2) treatment pathway across lines of therapy up to initiation of OCR, and 3) initial clinical experience in patients with ≥6 months follow-up data from OCR initiation.

Methods

Secondary data analysis using MSBase Registry data including patients with a confirmed diagnosis of MS and started OCR therapy within 3 months prior to or at time of MSBase eligible/initial visit. Descriptive statistics were used to analyze baseline patient characteristics' recorded within 3 months of OCR initiation, including demographics, disease course and duration, prior disease modifying therapies (DMT), and EDSS. Occurrence of relapse was analyzed in patients with ≥6 months follow-up data from OCR initiation.

Results

As of 4^th June 2020, MSBase included 2531 patients newly treated with OCR, of whom 1679 had an EDSS evaluation within 3 months of OCR start. There were 1185 patients with RRMS, 236 with SPMS, and 183 with PPMS. Median age at OCR initiation was 41.9 years, 49.5 years, to 50.1 years in RRMS, SPMS, and PPMS, respectively. Mean disease duration from symptom onset up to OCR initiation was longer in SPMS (19.7 years) than in RRMS (10.6 years) and PPMS (9.7 years). OCR was initiated as first line therapy in 17.5%, 5.5%, and 54.2% of RRMS, SPMS, and PPMS patients respectively. Most frequent previous DMT’s in RRMS were fingolimod (25.7%) and natalizumab (23.5%). 693 patients with RRMS had ≥6 months follow-up during OCR exposure. Of these, 643 remained relapse free (93%; 95% CI 86.0, 100.0) over a mean OCR exposure of 1.23 years. The annualized relapse rate (ARR) was 0.08 (95% CI 0.06-0.10), compared to an ARR of 0.85 in the 24 months pre-OCR start. In the overall cohort, treatment persistence at 12 and 24 months was 98.4% (95% CI: 97.3-9.1%) and 92.5% (95%CI 89-95%), respectively.

Conclusions

This study characterizes an international population of patients with RRMS, PPMS, and SPMS newly treated with OCR in a real-world clinical setting. First-line use was uncommon in RRMS and SPMS. During OCR treatment, ARR was below 0.1, and OCR discontinuations were very rare.