Studies done before the use of disease modifying therapy can be used as a general guide of what happens to someone with MS without treatment but have limitations which may lead to their presenting a worst-case scenario. One limitation relates to how patients were chosen to be followed in older studies. These studies frequently relied on clinical criteria to diagnose MS. Current diagnostic techniques which use MRI imaging and newer laboratory tests may diagnose earlier and milder cases of MS which one would not expect to worsen as quickly as patients from the historical studies. Current diagnostic techniques may also allow us to separate out MS mimics such as a disease called Neuromyelitis optica (NMO) which may have a worse outcome. If these MS mimics could be removed from the older studies, the outcome of patients in these studies may have been better. Two other reasons to think that outcomes for contemporary MS patients may be better than for historical patients are the widespread use of disease modifying therapies which hopefully are changing the time course and outcome of MS and newer medical treatments which in addition to the disease modifying therapies may help slow down disability accumulation.
Some studies suggest the natural history of MS may be changing for the better. A large retrospective study of patients in the Swedish MS. Registry in 2017 found that over the prior 15 years, the risk for a patient with relapsing-onset MS of becoming moderately disabled (EDSS 3) decreased by an average of 3% per year; of becoming severely disabled (EDSS 4) by 6% per year and to require the use of a cane or walker (EDSS 6) by 7% per year. Compared to someone diagnosed with MS in 2005, a person diagnosed with relapsing-remitting MS in 2010 had a 14%, 26%, and 30% lower risk of becoming moderately disabled, severely disabled or requiring the use of a cane or walker. Relapsing-remitting MS patients who were male, had more clinic visits and were older at onset of MS had the highest risk of achieving these milestones. These trends did not apply to patients with progressive-onset MS. (Belk 2019)[vii]
This study could not tell why more recently diagnosed patients had a lower risk of progression. Most of the relapsing-remitting MS patients were treated with disease modifying therapies but the study was not structured to determine if this was the reason for their results. [viii]Aside from the use of disease modifying therapies, another possibility was that newer technology such as the MRI and possible changes in the criteria for diagnosis of MS led to milder or earlier cases of RMS being enrolled in the registry at later times in the study. Other potential explanations include changes in health behaviors or environmental exposures such as smoking, vitamin d deficiency, improvements in MS care, improvement in the recognition and care of MS complications, as well as of infections and other coexisting medical conditions.