Multiple sclerosis (MS) is (1) one of the most prevalent demyelinating conditions affecting nearly 100,000 people across Canada. On average, 8 women and 3 men are diagnosed with MS every day in Canada (2).

Therapeutic decisions in MS are cognitively demanding and a complex task partly because of the wide variety of available disease modifying agents that are each associated with different efficacy and safety profiles (3, 4). Furthermore, MS treatment options available in Canada have doubled in the last 10 years (5). Given the limited training that physicians are exposed to with respect to risk management and decision-making processes, in dynamic treatment landscapes, treatment decisions may be inadequate, leading to suboptimal patient care and overall poorer outcomes (6, 7). It can also be challenging for neurologists to balance the immediate management of treatment side effects (8) with the longer-term risks of MS disease progression and on the patient and on society (9). A more proactive management strategy, including earlier use of high-efficacy DMTs and close monitoring of the clinical and radiological response to treatment is recommended to slow the progression of physical and cognitive impairments in patients with relapsing-remitting multiple sclerosis (RRMS) (10–12). Treatment escalation has been shown to reducing relapse rates, disability progression, and MRI activity (13).

Therapeutic inertia (TI) is a term which was introduced in 2006 to define the absence of treatment initiation or intensification in patients when treatment goals are unmet (14–16). In the context of MS, TI is defined as the lack of treatment initiation or escalation when there is evidence of disease activity, based on clinical course and neuroimaging markers (3, 17, 18). TI usually affects 30–70% of clinicians caring for patients with chronic conditions (14–16). Physician factors (e.g., low tolerance to uncertainty, status quo bias) are considered to be the main contributors to TI, but remain poorly studied in MS (4, 19, 20).

We hypothesized that TI affects at least 50% of Canadian Neurologists but lower than in other countries, with personal attributes (e.g., age, risk preferences) influencing treatment decisions.

Accordingly, our goals were: (i) To evaluate factors associated with TI amongst neurologists caring for MS patients across Canada; (ii) to compare the prevalence of TI in neurologists in Canada to TI observed in neurologists from Argentina and Chile (historical controls from prior studies).

Of the 108 neurologists from across Canada who were invited to participate in the study, 78 cooperated (cooperation rate: 72.2%) and 55 (completion rate: 50.9%) completed the study. We found no significant difference in age, sex, and years of experience between participants who completed and those who did not complete the study.

Overall, the mean age (SD) was 38.3 (±14.9) years; 26 (47.3%) were female. Thirty-one participants (56.4%) primarily focused their practice on MS care. On average, participants had 13 (±11.2) years of experience and assessed 22.2 (±14.6) MS patients per week. Table 1 summarizes baseline characteristics of the study population.

TI was present in 60.0% of participants in at least one case scenario. Thirteen participants (23.6%) showed TI in two or more case-scenarios. The mean TI score was 0.98 (±1.15). The analysis of individual responses revealed that TI was present in 12.3% of participants' responses (54/440).

For the risk assessment, the median value was 200 dollars (interquartile range 200–220) of safe earnings (instead of the 50/50 gamble of winning $400/$0), and 15 years (interquartile range 15–16) of survival without treatment. Participants who chose over 15 healthy years of survival without treatment (instead of 20 years with a 20% probability of side effects) had higher TI scores (mean TI score 1.47 vs. 0.73; p = 0.03). There were no differences in the TI score by risk assessment in the financial domain (mean TI score 1.06 vs. 0.95; p = 0.74).

The multivariate analysis revealed that older age (β 0.05, 95%CI 0.008–0.085; p = 0.018), less years of experience (β -0.06, 95%CI -0.11 to -0.03; p = 0.04) and inclination to opt for no treatment change when there is a risk of disease progression (β 0.10, 95%CI 0.01–0.19; p = 0.043) were independent predictors of TI (Figure 1).

TI is a common phenomenon in the management of MS patients (4). In the present study comprising neurologists with expertise in MS care from across Canada, TI was observed in 6 out of 10 participants. On average, for every 8 case-scenarios that warranted treatment escalation (or initiation), TI was demonstrated in one case. Factors most relevant to demonstrating TI were older age, lower years of experience, and willingness to accept risks of disease progression by avoiding treatment change in spite of the availability of more effective treatments.

Of interest is the comparison of TI in neurologists from Canada vs. that of neurologists from other countries (Argentina, Chile, and Spain) (22). Our analysis revealed that Canadian participants had a significantly lower TI. The underlying causes are unknown and warrant further studies. Cultural and practice-based differences, adherence to MS guidelines, and policy funding for DMTs may potentially explain our findings.

Our study has some limitations. First, the sample size is small, but representative of prescribers of MS agents from across Canada. Second, some participants' responses may reflect local administrative or health policy limitations in the prescription of disease modifying agents. Third, we were not able to compare baseline differences among countries to identify potential explanatory factors influencing TI.

Despite these limitations, our study suggests that TI affects at least 6 out of 10 neurologists caring for MS patients and is observed as frequently as 1 in 8 case-presentations when evidence of disease activity warranting treatment intensification. These findings, if confirmed in larger studies, have significant implications from a clinical care perspective, and suggest that educational interventions targeting the identified factors that influence TI may be warranted.

Future directions would include a larger study including several countries to identify factors and health system differences influencing TI. Moreover, future studies should also identify how neurologists weigh different factors (e.g., years since the MS diagnosis, number and severity of relapses, MRI findings, patients' preferences etc.) when making therapeutic decisions. Such information could help improve our understanding of clinical decision making in MS and may inform educational interventions that can ultimately lead to better outcomes in MS care.

GS is supported by the Heart and Stroke Foundation Career Scientist Awards following an open peer-reviewed competition. JO has received research funding from the MS Society of Canada, National MS Society, Brain Canada, and Biogen-Idec. JO has received personal compensation for consulting or speaking from EMD-Serono, Sanofi-Genzyme, Biogen-Idec, Roche, and Novartis.

GS: study concept and design, creation of the educational intervention, acquisition of data, analysis and interpretation of the data, and obtaining funding. MT: study implementation, interpretation of the data, and critical revision of the manuscript for intellectual content. FB, DS, and AM: interpretation of the data, critical revision of the manuscript for intellectual content. FC and MF: critical revision of the manuscript for intellectual content. XM and JO: supervision of MS case-scenarios, interpretation of the data, critical revision of the manuscript for intellectual content.