An international study finds multiple sclerosis treatments have long-term benefits, and that early treatment is important. The Royal Melbourne Hospital and University of Melbourne-led study is the first to provide evidence that the currently available therapies can delay progression of disability in multiple sclerosis. It showed that early treatment – particularly within five years of onset – delayed the secondary progressive stage of MS, which is characterised by an ongoing increase of disability.
Currently, more than 23,000 Australians are living with MS.
The conversion to the secondary progressive stage of MS is characterised by worsening of physical and mental capacity and reduced quality of life. Therefore, the capability to delay this progression of disability represents an important outcome for people living with multiple sclerosis.
The study was led by the Clinical Outcomes Research unit (CORe) at The Royal Melbourne Hospital and University of Melbourne in collaboration with the University of Cambridge. The international study used data from 1,555 patients, from 68 neurological clinics across 21 countries.
One of the study leads, Associate Professor Tomas Kalincik, head of the MS Service at The Royal Melbourne Hospital and CORe at the University of Melbourne, said that the study showed how important it is to treat MS pro-actively. “People who converted from relapsing MS to secondary progressive MS experience gradual and mostly irreversible worsening of disability.
“Most of the therapies that we use to treat MS have no effect once people have converted to secondary progressive MS. This study shows us how important it is to treat relapsing MS early and pro-actively,” Kalincik said.
Royal Melbourne patient Gowri was diagnosed with MS when she was in her 20s. She now has monthly infusions to treat her MS. She is pleased that doctors have the data to prove that current treatments are effective.
“It’s fantastic – it makes you feel very grateful that the treatment is working,” she said. “I had a great General Practitioner who referred me straight away to a neurologist. My treatment started very quickly.”
“This year will be 20 years since I was diagnosed, and even though I have some symptoms and I have been in hospital – particularly after the birth of my daughter, I’m able to work, catch up with friends and have a normal life,” Gowri said.
Kalincik said the results are reassuring for neurologists and patients with MS. “This study shows that the therapies they have been treated with for many years, significantly improve the quality of their lives over the long-term,” he said.
Importance: Within 2 decades of onset, 80% of untreated patients with relapsing-remitting multiple sclerosis (MS) convert to a phase of irreversible disability accrual termed secondary progressive MS. The association between disease-modifying treatments (DMTs), and this conversion has rarely been studied and never using a validated definition.
Objective: To determine the association between the use, the type of, and the timing of DMTs with the risk of conversion to secondary progressive MS diagnosed with a validated definition.
Design, Setting, and Participants: Cohort study with prospective data from 68 neurology centers in 21 countries examining patients with relapsing-remitting MS commencing DMTs (or clinical monitoring) between 1988-2012 with minimum 4 years’ follow-up.
Exposures: The use, type, and timing of the following DMTs: interferon beta, glatiramer acetate, fingolimod, natalizumab, or alemtuzumab. After propensity-score matching, 1555 patients were included (last follow-up, February 14, 2017).
Main Outcome and Measure: Conversion to objectively defined secondary progressive MS.
Results: Of the 1555 patients, 1123 were female (mean baseline age, 35 years [SD, 10]). Patients initially treated with glatiramer acetate or interferon beta had a lower hazard of conversion to secondary progressive MS than matched untreated patients (HR, 0.71; 95% CI, 0.61-0.81; P < .001; 5-year absolute risk, 12% [49 of 407] vs 27% [58 of 213]; median follow-up, 7.6 years [IQR, 5.8-9.6]), as did fingolimod (HR, 0.37; 95% CI, 0.22-0.62; P < .001; 5-year absolute risk, 7% [6 of 85] vs 32% [56 of 174]; median follow-up, 4.5 years [IQR, 4.3-5.1]); natalizumab (HR, 0.61; 95% CI, 0.43-0.86; P = .005; 5-year absolute risk, 19% [16 of 82] vs 38% [62 of 164]; median follow-up, 4.9 years [IQR, 4.4-5.8]); and alemtuzumab (HR, 0.52; 95% CI, 0.32-0.85; P = .009; 5-year absolute risk, 10% [4 of 44] vs 25% [23 of 92]; median follow-up, 7.4 years [IQR, 6.0-8.6]). Initial treatment with fingolimod, alemtuzumab, or natalizumab was associated with a lower risk of conversion than initial treatment with glatiramer acetate or interferon beta (HR, 0.66; 95% CI, 0.44-0.99; P = .046); 5-year absolute risk, 7% [16 of 235] vs 12% [46 of 380]; median follow-up, 5.8 years [IQR, 4.7-8.0]). The probability of conversion was lower when glatiramer acetate or interferon beta was started within 5 years of disease onset vs later (HR, 0.77; 95% CI, 0.61-0.98; P = .03; 5-year absolute risk, 3% [4 of 120] vs 6% [2 of 38]; median follow-up, 13.4 years [IQR, 11-18.1]). When glatiramer acetate or interferon beta were escalated to fingolimod, alemtuzumab, or natalizumab within 5 years vs later, the HR was 0.76 (95% CI, 0.66-0.88; P < .001; 5-year absolute risk, 8% [25 of 307] vs 14% [46 of 331], median follow-up, 5.3 years [IQR], 4.6-6.1).
Conclusions and Relevance: Among patients with relapsing-remitting MS, initial treatment with fingolimod, alemtuzumab, or natalizumab was associated with a lower risk of conversion to secondary progressive MS vs initial treatment with glatiramer acetate or interferon beta. These findings, considered along with these therapies’ risks, may help inform decisions about DMT selection.
J William L Brown; Alasdair Coles; Dana Horakova; Eva Havrdova; Guillermo Izquierdo; Alexandre Prat; Marc Girard; Pierre Duquette; Maria Trojano; Allesandra Lugaresi; Roberto Bergamaschi; Pierre Grammond; Raed Alroughani; Raymond Hupperts; Pamela McCombe; Vincent Van Pesch; Patrizia Sola; Diana Ferraro; Francois Grand’Maison; Murat Terzi; Jeannette Lechner-Scott; Schlomo Fletcher; Mark Slee; Vahid Shaygennejad; Eugenio Pucci; Franco Granella; Vilija Jokubaitis; Mark Willis; Claire Rice; Neil Scolding; Alastair Wilkins; Owen R Pearson; Tjalf Ziemssen; Michael Hutchinson; Katharine Harding; Joanne Jones; Christopher McGuigan; Helmut Butzkeuven; Thomas Kalincik; Neil Robertson