A major international phase III clinical trial, led by Queen Mary University of London, has found that ocrelizumab – a medication already prescribed to some patients with MS – significantly slows disability progression in people with primary progressive multiple sclerosis (PPMS), including older patients and those with more advanced disease who are wheelchair users.
The findings of the ORATORIO-HAND study, involved over 1,000 patients across 22 countries, making it the largest placebo-controlled treatment trial to date in a broad population of people with PPMS, were published today (28 May) in The Lancet.
Overall, the study found that ocrelizumab significantly reduced disease progression across several important disability measures. The results show that patients treated with ocrelizumab had a 30 per cent lower risk of disability progression compared with patients who received a placebo. The treatment also reduced the worsening of hand and upper-limb function by 41 per cent at 12 weeks and reduced the risk of requiring a wheelchair by 52 per cent among those who were still unable to walk or move about freely at the start of the study. Researchers found that the treatment effect of ocrelizumab was even greater in patients who showed signs of inflammatory disease activity on baseline MRI scans, with a 55 per cent reduction in the risk of disability progression in this group.
PPMS, a form of MS in which disability worsens over time, affects between 10 and 15 per cent of people with the condition. Unlike relapsing forms of MS, treatment options for PPMS remain limited, and there is ongoing debate about whether people with more advanced disease are still likely to benefit from treatment. This study goes a long way to settle that debate.
ORATORIO-HAND was specifically designed to address this question. Previous major studies often exclude patients aged 55 and above or those with advanced disability. In contrast, this study included patients up to the age of 65 and many with substantial mobility impairment and advanced disease progression.
In the study, researchers focused on walking ability and assessed upper-limb function using the 9-Hole Peg test, which measures hand and arm dexterity. They note that this method is particularly important because preserving hand function can have a major impact on independence, communication, and quality of life for people living with advanced PPMS. In a separate survey conducted by Professor Giovannoni and colleagues at Queen Mary, people with worsening MS prioritised upper-limb and hand function over lower-limb function, citing independence, grooming, and toileting as their reasons.
Researchers note that their findings suggest ocrelizumab could benefit a wider patient population than currently has access to the medication, which will lead to changes in the way MS is managed on the NHS, and it will change future trial design for progressive MS
Gavin Giovannoni, lead author and Professor of Neurology at Queen Mary, said: "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. Our study suggests we should think differently about what successful treatment looks like in advanced MS and that we shouldn't assume a lack of benefit in certain groups. The O'HAND study changes the way we manage and think about MS."
Dr Catherine Godbold, Senior Research Communications Manager at the MS Society, said: "The results of the ORATORIO-HAND trial are incredibly positive to see. MS can be debilitating, exhausting and unpredictable, and hand and arm function is essential for helping people to remain independent. Many previous trials have focused solely on walking ability as a measure of whether a drug is effective. But trials like this are vital in helping us find treatments for everyone.
"Ocrelizumab is already used as a treatment for active relapsing MS and early primary progressive MS. These results could mean it is made available for more people with primary progressive MS, who don't currently have access to any treatment options. The key now is how we work together to see these findings translated into clinical practice."
