With limited treatment options, physicians often misclassify SPMS as RRMS
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Patients with secondary progressive MS on disease-modifying treatments often are clinically misclassified as having relapsing-remitting MS, most likely because they are not reassigned categorically until after conversion has occurred.
These findings call into question the use of time to secondary progressive MS (SPMS) conversion as an outcome measure in comparative effectiveness studies that use real-world data, according to the findings presented at MSVirtual2020.
“Until recently, disease-modifying treatment [DMT] options for MS patients with a secondary progressive course were limited, leading to the common practice of off-label treatment with drugs approved for relapsing-remitting MS [RRMS],” the researchers wrote. “We previously showed that applying objective algorithms tends to increase the proportion of SPMS in MS registries, suggesting that SPMS is under-diagnosed in clinical practice, possibly related to available treatment options.”
Jan Hillert, MD, PhD, professor and senior physician in the department of clinical neuroscience at the Karolinska Institute in Sweden, and colleagues examined the characteristics of patients clinically classified as RRMS who were then reassigned following the use of an algorithm-based SPMS assignment method. They also used a data-driven assignment method in the form of a decision tree classifier based on age and last Expanded Disability Scale Status, or EDSS. Hillert and colleagues used data from MS registries in the Czech Republic, Denmark, Germany, Sweden and the United Kingdom.
To be included in the study, patients were required to have a RRMS or SPMS diagnosis, with an age of 18 years or older at the start of the study period. The study ran from Jan. 1, 2017, through Dec. 31, 2019.
The analysis included 8,372 patients with RRMS who were reassigned as having SPMS, including 1,566 from Denmark, 1,958 from the Czech Republic, 2,906 from Germany, 648 from Sweden and 1,294 from the United Kingdom. This increased the overall proportion of patients with SPMS from 17% to 31%, according to Hillert and colleagues. Characteristics of reassigned patients included younger age, older age at the time of MS onset and faster progression to SPMS.
“Patients [who were] reclassified were a bit younger, which is expected. They also seemed to have a later age at onset, which is surprising to some extent,” Hillert said during his presentation. “Age at conversion was inconsistent between the registries, as was age from MS onset to age at conversion. We think, though, that the reason for higher age at onset is bias and not biological difference. This probably signifies that it takes some time for clinicians to have the nerve to classify patients, so to speak, for SPMS. That is a bias that is important to consider.”
Study findings demonstrated that the overall proportion of patients clinically assigned SPMS who were receiving DMTs was 36%, but the proportion varied between registries (Czech Republic, 18%; Denmark, 35%; Germany, 50%; Sweden, 40%; and United Kingdom, 12%). The proportion of patients on DMTs was higher (69%) among those with RRMS who were reassigned as SPMS (OR = 4; P < .00004). The researchers observed less variation between regions in this group (Czech Republic, 71%; Denmark, 68%; Germany, 78%; Sweden, 80%; and the United Kingdom 40%).
“This is more interesting,” Hillert said. “Those patients [who] are reclassified are, to a much greater extent, on DMTs compared with clinically assigned SPMS patients. It is very clear that there is a tendency for clinicians not to reassign RRMS patients to SPMS if they are on treatment.”
The tendency not to reassign these patients may be related to treatment constraints in SPMS, he continued. While the issue could decrease over time as more treatment options for patients with SPMS are developed, Hillert called it “a clear problem” for existing registries.
“If you are to use the clinical registries dataset in an outcome study of any kind, like a comparative effectiveness setting for instance, patients on DMTs may come out more favorable because of the bias. You cannot really use time to SPMS conversion in effectiveness studies in a way that is actually practiced,” Hillert said. “We believe that these objective classification methods should be considered in scientific analyses of MS populations and datasets in the real-world setting and for control activities in health care planning for MS.”
Perspective
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Neurologists who treat MS are often challenged by determining the point at which an individual transitions from the relapsing-remitting to the secondary progressive stage of disease. This is due, in large part, to the lack of widely accepted objective guidelines, as well as the heterogeneity of the disease.
In the current study, investigators applied objective algorithms across five European MS registries to identify patients with SPMS. Approximately 14% were reclassified as having SPMS, increasing the overall proportion of SPMS from 17% to 31%. Unsurprisingly, the reassigned patients tended to be younger, had experienced a quicker progression to SPMS, and almost 70% were being treated with a DMT.
This study highlights the dilemma that a significant percentage of patients with SPMS, particularly those with a more aggressive clinical course, may be maintained on a DMT past the point when such therapy is effective. As the authors note, another implication of their findings is that time to SPMS conversion may not be a useful outcome measure in comparative effectiveness studies using real-world data.
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Hillert J, et al. Abstract PS05.04. Presented at: MSVirtual2020; Sept. 11-13, 2020 (virtual meeting).
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