The uncertainty period preceding the clinical defined SPMS diagnosis and the applicability of objective classifiers - A Danish single center study

BACKGROUND: The clinical transition from relapsing-remitting multiple sclerosis (RRMS) to secondary progressive MS (SPMS) is often related to a period of diagnostic uncertainty delaying diagnosis. With emerging treatment options for SPMS how to identify RRMS patients at risk of SPMS and when to assign a SPMS diagnosis has become a matter of growing clinical concern. This study aimed to determine the period of diagnostic uncertainty among Danish MS patients. Secondly, this study examined the performance of two objective classifiers in a longitudinal setting regarding their ability to shorten the period of diagnostic uncertainty.

METHODS: By using the Danish Multiple Sclerosis Registry, we identified all patients linked to Rigshospitalet with clinically assigned SPMS from 2010 to 2021. We reviewed all patient records and identified the first mentioned sign of progression (FMP). The time between the dates of FMP and clinically assigned SPMS was defined as the period of diagnostic uncertainty. Secondly, we applied two objective classifiers (the Karolinska Decision tree and the MSBase criteria) to generate suggested transition dates and compared them to the ones obtain from the patient records. Detailed descriptions of the population were made at all mentioned timepoints.

RESULTS: In total 138 patients were included. We found a median period of diagnostic uncertainty of 2.12 years. The objective classifiers generated a median suggested transition date 3.44 and 4.48 years earlier than the date of clinically assigned SPMS, but they only provided an earlier SPMS transition date in 50.72% and 55.80% of cases.

CONCLUSIONS: Our findings emphasize the uncertainty related to the transition from RRMS to SPMS illustrating the need of an improved diagnostic approach. Objective classifiers might have the potential to help reduce the period of diagnostic uncertainty in the future, but in their current form they do not perform satisfactorily enough to solve all difficulties related to detecting SPMS-transition.