Over 1,000 patients across 22 countries participated in a landmark trial that challenges a long-held assumption in neurology: that people with advanced multiple sclerosis have little to gain from treatment. The ORATORIO-HAND study, led by Queen Mary University of London and published in The Lancet, found that ocrelizumab—a medication already available to some MS patients—significantly slows disability progression even in people with primary progressive MS (PPMS) who are older, in wheelchairs, or far along in disease progression.
Primary progressive MS affects between 10 and 15% of people with the condition, and unlike relapsing forms of the disease, treatment options have remained stubbornly limited. Previous major trials often excluded patients aged 55 and above or those with advanced disability, leaving a crucial gap in medical evidence. The ORATORIO-HAND study was specifically designed to fill that gap, enrolling patients up to age 65 with substantial mobility impairment and advanced disease.
The results are striking. Patients treated with ocrelizumab had a 30% lower risk of disability progression overall compared with those who received placebo. But the benefit grew even larger for certain groups: in patients showing signs of inflammatory disease activity on baseline MRI scans, the reduction in disability progression risk jumped to 55%. The treatment also reduced worsening of hand and upper-limb function by 41% at 12 weeks and cut the risk of requiring a wheelchair by 52% among those who were still unable to walk freely at the trial's start.
The focus on hand and arm function marks a deliberate shift in how researchers measure treatment success. A separate survey conducted by the study's lead author, Professor Gavin Giovannoni, found that people living with worsening MS actually prioritize upper-limb and hand function over lower-limb function, citing independence, grooming, and toileting as their reasons. Yet many previous trials had focused solely on walking ability. Preserving hand dexterity—measured in this study using the 9-Hole Peg test, which assesses how quickly patients can move pegs between holes—can have an outsized impact on quality of life and independence for people with advanced disease.
"These findings are important because they show that treatment can make a meaningful difference to people with more advanced forms of MS and can help preserve hand and arm function, which is important for maintaining independence, daily activities and quality of life," Giovannoni said. He added that the study suggests we should reconsider what successful treatment looks like in advanced MS and not assume certain groups won't benefit.
The implications ripple outward quickly. Researchers note that their findings suggest ocrelizumab could benefit a wider patient population than currently has access to it, with potential changes to how MS is managed on the NHS and how future progressive MS trials are designed. Dr. Catherine Godbold of the MS Society called the results "incredibly positive," noting that trials like this are vital in helping find treatments for everyone with MS, not just those with relapsing forms or early disease.
For people living with advanced primary progressive MS, the message is clear: the conversation about their care has fundamentally shifted.