High incidence and increasing prevalence of multiple sclerosis in British Columbia, Canada: findings from over two decades (1991–2010)

The prevalence of MS in BC, Canada has risen steadily and substantially, from 78.8/100,000 in 1991 to 179.9/100,000 in 2008. The incidence rate in BC remained stable over the study period, averaging 7.8 per 100,000 new cases of MS per year between 1996 and 2008, which is high relative to other parts of the world [1‐4]. The prevalence sex ratio increased over time; however, the incidence sex ratio, which averaged 2.8:1, did not increase.

Methodological differences make direct comparisons with earlier studies of MS prevalence in BC difficult. Other than a study based on self-reported MS [21], the last province-wide estimate of MS prevalence, which used clinically confirmed definitions, was 93.3/100,000 in 1982 [22]. Our estimates for 1991 (78.8/100,000) and 1992 (101.1/100,000) are compatible with this estimate from 10 years earlier. There are no previous estimates of MS incidence in BC with which to compare our observations. However, using the same validated administrative MS case definitions age standardized to the same population, a similar annual incidence rate was recently found in central Canada [10] (11.4/100,000 in Manitoba using the more sensitive case definition). While a somewhat higher annual incidence was found in eastern Canada [11] (9.8/100,000 in Nova Scotia using our primary case definition), the 95 % confidence intervals overlapped with those in our study. BC, Manitoba and Nova Scotia are home to approximately 19 % of the Canadian population; extrapolating the combined estimate from these provinces (weighted by their relative population) to Canada, which had a population of 35.5 million in 2014, would mean that approximately 3000 new MS cases are diagnosed each year, or 8 new cases per day. Furthermore, extrapolating the combined prevalence estimate (200/100,000) from the three provinces would mean that approximately 71,000 people are living with MS in Canada.

Our observations that the prevalence of MS has been increasing by approximately 4.7 % per year in BC, and that the age of the prevalent population has risen have important implications for broader society, including governments and health care planners. We also found a gradual increase in the proportion of women to men living with MS; this is compatible with recent observations from elsewhere in Canada [10, 11] and the UK [23], and is likely due to the changing demographics (older mean age) of the general population and the greater life expectancy of women compared to men.

The rising prevalence in BC cannot be explained by increasing numbers of new MS cases; our incidence rates remained relatively stable over the 13-year period despite changes in MS diagnostic criteria [24] and increasing availability of disease-modifying drugs. While this seems in contrast to some other regions of the world where recent increases in incidence rates have been reported [5], a stable incidence rate has also been found over a similar time period in other Canadian provinces [10, 11, 19, 25, 26] and the UK [23]. Taken together with our findings, this suggests that the incidence of MS has stabilised in some areas over recent years. In the absence of increasing incidence, the rising prevalence may reflect longer disease duration due to earlier diagnosis, improved survival with MS or both. Survival has improved for both the BC general population and for people with MS in BC over the past 30 years [27]. Similarly, improved survival has been found in other MS populations, including those from Denmark [28] and Norway [29]. Immigration of prevalent cases can also influence prevalence trends and the population of British Columbia increased by nearly 30 % between 1991 and 2008, mostly due to immigration from other Canadian provinces and other countries. The prevalence estimates include MS cases that were resident throughout, as well as those that immigrated to BC, during the observation period. Newly immigrant prevalent cases would have contributed to the increasing prevalence over time if there was a greater proportion of MS cases among those immigrating to BC.

The average age at the time of the incident MS-related claim was 44 years. This age is comparable to that recorded in other Canadian provinces [10, 11] and was found to be within 3 years of the MS diagnosis date from medical charts or by personal report for 74 and 76 % of cases, respectively [10]. It is also equivalent to that identified as the first date of diagnosis in the General Practice Research Database for cases of MS in the UK [23]. While the date of diagnosis, or of first medical recognition, is frequently used to measure MS incidence [2‐4], symptom onset can often occur several years before the disease is first recognized or diagnosed.

Notably, while others have reported increases in the incidence ratio of women to men with MS [6], we found no evidence of such a trend in BC. Rather, we observed a decrease in this ratio over time, although the absolute differences were small. Nonetheless, the more consistently observed sex differences for MS were evident; nearly three quarters of incident cases in BC were women and men were approximately 3 years older than women at the time of the first MS-related claim reflecting typical differences in onset age between sexes.

We observed a small difference in the distribution of cases across the socioeconomic quintiles, with a greater proportion of both incident and prevalent cases in the upper quintiles and fewer in the lower. Similar observations have been made in the past [30‐34], although others have reported either no relationship or a negative association with SES [35].

Approximately, one-third of incident or prevalent MS cases filled a prescription for a DMD during the study period, stabilizing from the year 2000 onwards. This proportion may seem low, particularly when compared to a previous estimate (73–85 %) derived from a volunteer sample of patients recruited from Canadian MS treatment centres [36]. However, our proportion was derived from population-based rather than clinic-based data, the first DMD (interferon beta-1b) was only approved for use in Canada in 1995, and not all individuals with MS would have been eligible for treatment (including those unable to walk, those without relapses and those with a primary progressive disease course). Thus, it is likely that our data provide a realistic representation of DMD use in the British Columbian MS population over the study period.

The strengths of our study include the use of administrative health data, which represents the entire BC population, and spans nearly two decades allowing us to assess temporal trends. Furthermore, we used two previously validated MS case definitions to generate these estimates [10, 11]. The primary definition was identified as the best in terms of balance between specificity and sensitivity among candidate validated MS case definitions [11]. The secondary definition generated higher estimates due to its greater sensitivity, but may have included a greater proportion of false positives. Estimates generated by the primary definition could be more useful when it is important to minimize the risk of including people without MS, whereas the estimates from the more sensitive definition are likely more useful for estimating burden of disease and for health care planning. Although these MS case definitions were not validated specifically using the BC administrative data, the algorithms have been validated in Nova Scotia and Manitoba [10, 11]. Furthermore, similar 7-claim administrative case definitions of MS derived from administrative data in Ontario, Canada were validated in a primary care dataset in that province and found to have excellent performance [18]. The structure of the Canadian public health care system and the methods for coding physician and hospital visits in administrative health data are consistent between these three provinces and BC, which suggests that the case definitions would perform well and can be reliably applied in BC. The BC administrative health databases have been used, both independently and combined with equivalent data from other Canadian provinces, to identify and study other chronic diseases such as diabetes and hypertension [37‐39].

Health administrative data have limitations. Although we allowed a five-year claim-free run-in period to capture incident cases, it remains possible that prevalent benign MS cases that rarely interacted with the medical system were misclassified as incident. Ascertainment is a common problem with MS incidence studies due to the inevitable time-lag between symptom onset and recognition of the disease; the estimated incidence may be affected by incomplete ascertainment towards the end of follow-up. Similarly, the prevalence estimates for the earliest years (1991 and 1992) should be treated cautiously; atypical prevalent cases with infrequent contact with the medical system could have been missed in these years. On the other hand, although we had missing follow-up data for up to 254 potential MS cases and could not confirm that they met criteria with follow-up to 2010, the estimates were not notably impacted.

We were unable to consider ethnicity, or country of origin. Although most BC residents are of European ancestry, BC has a higher proportion of residents of non-European origin than other Canadian provinces. The proportion with European ancestry has declined over time, from 82 % of the BC population in 1996 [40] to 75 % in 2006 [41]; people of Asian ancestry represent the largest minority group. The somewhat lower MS incidence rate in BC compared to that in Eastern Canada [11] might be explained by differences in the ethnic composition of the source populations [41].

In summary, BC has a high incidence of MS which has remained stable for more than a decade. However, as elsewhere in Canada, the prevalence and the peak age of the MS population have increased significantly. Population-based administrative health databases and validated case definitions of MS using health claims data provide a reliable, accessible and cost effective means of monitoring the incidence and prevalence of MS.