Background

Use of disease-modifying therapies (DMTs) for the treatment of multiple sclerosis (MS) is driven by many factors that are not well understood. In March 2017, ocrelizumab (OCR), an intravenous humanized anti-CD20 monoclonal antibody (mAb), was approved in the United States for the treatment of relapsing-remitting MS (RRMS) and primary progressive MS (PPMS).

Objectives

To examine whether the type of MS patient being treated with OCR first line or as a first switch is changing over time in the United States.

Methods

Cross-sectional MS patient-level data were collected once-yearly from practicing United States neurologists from 2017 to 2020. Contributed chart review data were from MS patients either initiating their first DMT (2017 n=1,033; 2018 n=1,059; 2019 n=1,006) or switching to a new DMT (2018 n=1,035; 2019 n=1,003; 2020 n=1,009) within the prior three months. Analyses focused on new OCR starts (2017 n=70; 2018 n=107; 2019 n=102) and first switches to OCR (2018 n=60; 2019 n=85; 2020 n=90). Relapsing forms of MS (RMS) is defined as clinically isolated syndrome and RRMS.

Results

Overall use of OCR in treatment-naïve MS individuals has increased since 2017, with a decrease in PPMS offset by an increase in RMS. By 2019, OCR was the initial DMT choice in 7% of RMS individuals, while use decreased from 63% in 2017 to 35% of PPMS. Of all new OCR DMT starts evaluated in 2019, RMS made up 58% and PPMS 31%. OCR starts are increasingly female, with 65% of 2019 new start use among female MS patients. This pattern is seen for both RMS and PPMS, although is more marked for PPMS. Mean age of MS patients initiating OCR has decreased by 4.6 years since 2017. OCR use in those aged ≥56 years has fallen to 12% compared to 31% in 2017. Mean Expanded Disability Status Scale (EDSS) score decreased in the PPMS cohort who initiate OCR therapy, but increased in the RMS cohort.

Among MS individuals who made a first switch to OCR in 2018-2020, more switches were among RMS patients compared to PPMS. Switches to OCR are now most likely from first-line glatiramer acetate (GA; 39%), followed by dimethyl fumarate (18%). Switches from interferon beta have decreased from 33% to 17%. In PPMS, the second most common switch is from another mAb therapy to OCR (accounting for 24% of 2020 switches up from 11% of 2018 switches). First switches to OCR are increasingly among female MS patients (2020: 64% vs. 2018: 50%), especially among PPMS patients. Mean age and EDSS score have not changed significantly over time when assessed by total, MS subtype, or gender.

Conclusions

OCR initiation as a first-line agent is on the rise, driven by increased use among RMS patients, and is being used in younger MS individuals. First-line OCR use in females with PPMS has increased over time. Initial switches to OCR are increasingly coming from GA. The usage pattern of OCR in the United States is evolving and changing over time.

Background

There are currently two immune-reconstitution therapies (IRTs) licensed for relapsing multiple sclerosis (MS) - alemtuzumab (ALZ), an anti-CD52 monoclonal infusion, and cladribine (CdA), a short-course oral, T- and B-cell depletor.

Objectives

To review real world data of characteristics and disease-modifying treatment (DMT) history among EU and US patients switched to IRTs.

Methods

In 2019, 276 EU neurologists contributed online chart reviews for a retrospective audit of 1,266 MS patients who switched to a new DMT (ALZ: 77; CdA: 47) within the prior 3 months. In 2020, 204 US neurologists contributed 1,009 chart reviews (ALZ: 35; CdA: 21). Conducted at the .05 alpha level, independent samples t-test was used to test differences in means, and z-test (with Bonferroni correction) in proportions, between DMTs.

Results

Overall, IRT use was low, with slightly more patients switched to ALZ (EU: 6.1%; US: 3.5% of switch charts) than CdA (EU: 3.7%; US: 2.1%), except in Germany. While age, gender, recent relapse, and lesion counts did not differ by therapy or region, US patients treated with ALZ trended towards being diagnosed more recently compared to CdA-treated patients (mean: 30 vs. 68 months; p=0.058).

In the US, CdA was more likely than ALZ to be prescribed to patients with relapsing-remitting MS (RRMS) (86% vs. 60%; p=0.043) and trended towards being used less in RRMS patients with perceived risk for transition to secondary progressive MS transition (CdA: 17% vs. ALZ: 43%; p=0.077).

In both regions, most IRT switches were first DMT switches. In the EU, patients switched to CdA were more likely to have switched from an interferon (CdA: 28% vs. ALZ: 23%). In the US, glatiramer acetate more frequently preceded CdA (CdA: 38% vs. ALZ: 23%), while an anti-CD20 monoclonal antibody was more likely to have preceded ALZ (ALZ: 29% vs. CdA: 5%; p=0.030).

Conclusions

IRT treatment patterns in the EU and US are similar, with the exception of known differences in preceding injectable DMT use. In the US, patients are more likely to have been treated with anti-CD20 therapy before switching to ALZ than CdA, perhaps due to perceived differences in IRT efficacy profiles. ALZ is also more likely than CdA to be used among US patients diagnosed with, or at risk of transitioning to, progressive MS. Conversely, in the EU, the two IRTs are prescribed to very similar patient types.