REFINE-MS

After at least two years of standard 6-monthly ocrelizumab treatment, can the frequency of administration can be reduced without compromising disease control, while simultaneously reducing the risk of adverse events, mitigating healthcare costs, and improving patient quality-of-life and convenience.

REFINE-MS: A randomised, rater-blind, phase 3 trial to determine the optimal dose frequency of ocrelizumab for patients with relapsing remitting multiple sclerosis using a novel multi-arm multi-stage frequency-optimisation design

What is this study about?

Multiple sclerosis (MS) can cause episodes of new or worse symptoms, called relapses. Relapses happen when the immune system attacks the brain and spinal cord, which can lead to damage seen on MRI scans. Ocrelizumab is a treatment that reduces the immune cells that drive this inflammation. It has transformed MS care because it can strongly reduce new brain damage and help prevent relapses.

However, ocrelizumab also lowers the body’s ability to fight infections and may reduce how well vaccines work. There are also concerns about a possible increased risk of some cancers. It is expensive (about £19,160 per person per year, not including hospital and pharmacy costs or time off work). Most people receive ocrelizumab every 6 months, but its benefits may last much longer than that.

REFINE-MS will test whether people with relapsing-remitting MS who have been stable on ocrelizumab for a minimum of 2 years can take it less often and still keep their MS under similar control compared with the standard schedule of every 6 months. The study will also look at whether less frequent dosing reduces side effects and lowers NHS costs.

REFINE-MS will include 540 people with relapsing-remitting MS who have been receiving ocrelizumab every 6 months for at least two years and have had no relapses and no new MRI damage for at least 12 months. Everyone in the trial will continue ocrelizumab, but they will be assigned by chance to receive it at different frequencies: every 6, 9, 12, 15, or 18 months. The study is run in stages so it can safely identify the schedule that still works. It begins by comparing treatment every 6 months with treatment every 12 months, with an early review after the first 90 participants have completed one year. If taking ocrelizumab every 12 months appears to work as well as every 6 months, the trial will continue with all five frequency groups. If it works less well, the trial will stop using the 12, 15 and 18 months frequencies and will focus on comparing every 6 months with every 9 months. The study will follow participants for at least two years.

Type of study

Randomised trial

Contact details

MRCCTU.REFINEMS@ucl.ac.uk

Data Sharing

Data will be made available for sharing following publication of the primary outcome, in accordance with the InCTU controlled-access data-sharing policy. Researchers wishing to access REFINE-MS data should contact the Trial Management Group in the first instance. All data sharing will comply with the UK Data Protection Act 2018 and applicable information governance requirements. Biological samples collected as part of the mechanistic immunology sub-study will be destroyed at the end of the trial and will not be available for future research.

Who is funding the study?

NIHR Efficacy and Mechanism Evaluation Programme (EME)

When is it taking place?

May 2026- Dec 2030

Where is it taking place?

15-20 NHS clinics in UK

Who is included?

Participants, 18 years or over with relapsing remitting multiple sclerosis who are stable clinically and have been receiving Ocrelizumab treatment for at least 2 years.