What is ‘therapeutic inertia’?
A concept that surfaced a few years ago in MS is ‘therapeutic inertia’. What it means is that when it comes to MS therapy, there is a tendency either to remain at rest (i.e. not to start treatment) or to continue with the same medication indefinitely even if there is evidence that another treatment might be better.
Therapeutic inertia was first explored in a University of Toronto survey of neurologists in Spain, who were shown a series of MS cases and asked how they would treat them (Saposnik and colleagues. Front Neurol 2017;8:65). If a given patient wasn’t doing well on a given medication but the doctor said they wouldn’t change treatments, this was labelled ‘therapeutic inertia’. The doctors were well-practised in treating MS, seeing an average of 20 people a week. However, the survey found that 70% of the doctors had therapeutic inertia. Similar rates of inertia have since been reported in Canada (60%) and Chile (64%) (Saposnik and colleagues. Front Neurol 2018;9:781; Saposnik and colleagues. ECTRIMS 2018; abstract P959).
These apparently high rates of inertia should be interpreted with caution. What a doctor should do in a given case scenario is rarely black-and-white and the decision to use a more potent treatment is influenced by many factors. Some of the participants may have disputed whether a “bigger gun” was justified, but one “wrong” answer meant that the doctor was considered to have inertia. Indeed, the most recent study looked at this issue in a slightly different way. It found that about 20% of treatment decisions exhibited therapeutic inertia (Saposnik and colleagues. ECTRIMS 2018; abstract P362), which may be a better way of representing this issue.
There are many reasons why a doctor doesn’t offer a more potent therapy when the current medication isn’t doing its job. Some may be concerned about side effects with a more potent medication; others may think that the risks aren’t worth the extra effort to control MS; and some may be hesitant to rock the boat – if a person has settled into the routine of taking a medication, why make a change?
In some cases, the reason may be a disconnect between intention and action. A U.S. survey found that neurologists were evenly divided about how to treat MS – some favoured a slow, incremental approach, while others thought they should use the most effective therapy right away (Naismith and colleagues. ECTRIMS 2018; abstract P868). But when the researchers looked at what the two groups of doctors actually prescribed – there were no differences. Advocates for more effective therapies were no more likely to prescribe one of these drugs than their more conservative colleagues.
The University of Toronto group looked at the psychology of treatment decision-making and found that doctors were more likely to show therapeutic inertia if they didn’t handle ambiguity well. In the doctors’ minds, the known risks of a drug outweigh the unknown risk of disability worsening during the course of MS. And doctors are risk-averse – they tend to choose a drug with a lower probability of causing harm rather than a drug that may be more effective in reducing the harms caused by MS. A less risky but less effective therapy is the more prudent choice.
As a result, many people take Copaxone, which has not been shown to slow the development of disability. Far fewer people take Lemtrada, perhaps the most potent MS drug. Some people taking this medication develop serious side effects affecting their thyroid (about 5%), serious infections (about 3%) or other problems, and all will require monthly blood tests. But what it achieves is efficacy: 70% do not develop disability (and disability improves in about one-half of cases) over an 8-year period (Singer and colleagues. ECTRIMS 2018; abstract P913). These are the risks and benefits that a doctor (and the person with MS) must weigh when choosing a therapy.
Because of these possible risks, doctors often keep Lemtrada and other potent medications in reserve for people who are rapidly going downhill, but by then the damage caused by MS may well be irreparable. A recent study looked at people who started a high-potency drug right away rather than waiting a few years and found that greater potency had a better payoff: people starting earlier on Lemtrada, Ocrevus or Tysabri showed no change in their level of disability over the next 6 years whereas those on less effective medications had started to get worse disability (He and colleagues. ECTRIMS 2018; abstract P919).
The decision to start a given treatment doesn’t rest entirely in a doctor’s hands – it’s ideally shared with the person who will be taking the drug. And people with MS exhibit some therapeutic inertia of their own (Saposnik 2018). As the researchers noted, there is a human tendency to the status quo – a behaviour well-known to telephone companies, internet providers, insurance companies and other businesses. You may no longer watch TV because of Netflix, but it may be years before you cancel your cable service. In the case of MS, people who are newly-diagnosed may not want to start treatment, and those who are symptom-free for the most part may be loath to change medications. It’s only later, when they are clearly getting worse, that they may decide on a more effective therapy. This has been likened to starting an antibiotic only after you develop a high fever rather than when the infection was first detected.
Treatment decisions are complicated for everyone involved – the doctors who prescribe and the people who will need to keep filling that prescription for the foreseeable future. Choices that involve risk, the potential for loss or regret, or challenge how people see themselves are ripe for what has been called ‘decisional conflict’ (Wilkie and colleagues. ECTRIMS 2018; abstract P967). It’s hard to feel comfortable with the choices no matter what you decide. Most people with MS feel this inner conflict – especially if they’ve become dissatisfied with their current treatment or feel it isn’t doing much to control their MS. So if a medication isn’t doing all it can to slow disability, it’s important for people to have a frank discussion with their MS team to sort through the many options available.
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