MS treatment strategy: Hitting hard and early, or minimising risks through stepwise escalation?

ECTRIMS 2018

MS treatment strategy: Hitting hard and early, or minimising risks through stepwise escalation?

1969 1525 Mea Holm, PhD

With more than a dozen approved treatment options for relapsing-remitting multiple sclerosis (RRMS), treatment decision making is an increasingly complex task for neurologists. At ECTRIMS 2018, the topic on which disease-modifying treatment (DMT) to prescribe and when to switch DMTs was approached from two different angles: hitting hard and early with the most effective DMTs – which may be associated with high risks, or stratifying risk through stepwise escalation to more aggressive treatments depending on the individual disease course.

Hitting hard and early

After an introduction by Prof. Paulo Muraro (London, UK) on the mechanisms of immune modulation in MS and the currently available treatments, Prof. Gavin Giovannoni (London, UK) took the stage to urge neurologists to treat early with high-efficacy treatments. He based his case on findings that immune reconstitution treatments, such as mitoxantrone, alemtuzumab and haematopoietic stem cell transplantation (HSCT), have led to disease stabilisation for over ten years in some patients. This strategy may potentially represent a ‘cure’ from MS in a proportion of these patients. Given that the major inflammatory damage occurs within the first five years of the disease – and that the goal of treatment should be to prevent damage in the first place – he advocated early treatment and opposed ‘watchful waiting’.

Prof. Giovannoni further emphasised his position with data from the recent TOPAZ study, showing that treatment with alemtuzumab led to normalised annual brain volume loss in patients with MS to the levels expected for the general population. An impressive example of the success of the ‘hitting hard and early’ strategy was the case of a professional golfer with MS who is able to continue playing and displays no signs of disability 14 years after treatment with alemtuzumab.

“You have their brains in your hands, and it’s up to you to protect them,” ended Prof. Giovannoni, taking the stance that neurologists should protect brain health overall, including but not limited to early treatment with high-efficacy immune-resetting DMTs.

Stepwise escalation

Dr Daniel Ontaneda (Cleveland Clinic, Ohio, USA) in turn presented the advantages of risk mitigation through stepwise escalation. This approach relies on MS therapy initiation with low- to moderate-efficacy DMTs (interferon, glatiramer acetate), followed by escalation to more aggressive treatments in patients with persistently high disease activity. He argued that the goal of MS treatment is to prevent relapses and disability accrual without exposing the individual to potentially unnecessary risks. The risks that can be associated with the high-efficacy DMTs include rare infections of the brain and other organs, such as progressive multifocal leukoencephalopathy (PML), and malignancies.

Dr Ontaneda’s advice for neurologists was to closely monitor predictive measures – such as annualised relapse rates, disability scores, new lesions, and brain atrophy – early on in the disease course to help identify the patients that are likely to need treatment escalation. He emphasised that the jury was still out on whether treatment escalation was more or less effective than treating early with high-efficacy DMTs, and that head-to-head trials comparing these treatment strategies are needed – two such trials have recently been initiated (DELIVER-MS and TREAT-MS).

What was the audience’s verdict; hit hard and early, or stay safe and escalate? A show of hands indicated an approximated 50:50 split in the opinions of attending neurologists. The majority, however, supported basing treatment decisions on individual risk factors.

Brainwork is supported by unrestricted grants from: