Citation: Engelhard J, et al. Multiple sclerosis by phenotype in Germany. Mult Scler Relat Disord. 2022 Jan;57:103326. doi: 10.1016/j.msard.2021.103326. PMID: 35158442.

Purpose/Hypothesis

Retrospective, observational, cohort study to compare the prevalence, drug utilization (the types of MS treatments prescribed), and comorbidities (associated clinical conditions) across three MS phenotypes, RRMS, PPMS, and SPMS

Database

The researchers queried German health insurance database for records from 2010 to 2017 (8-year period) containing 4.3 million patients’ records (~5% of total German population). The current classification of MS phenotypes (revised in 2013) has been included in the German diagnostic coding system since 2005 (ICD-10-GM 2005).

RESULTS

• Between 2010 and 2017, the proportion of 3 MS phenotypes remained similar: RRMS, 73.0% vs 79.0%; PPMS, 8.5% vs 6.0%; SPMS, 18.6% vs 14.7%
• Prevalence has increased since 2010: RRMS by 113% (from 86 to 183 per 100,000); PPMS by 40% (from 10 to 14 per 100,000); and SPMS by 55% (from 22 to 34 per 100,000)
• Mean age at diagnosis has increased significantly since 2010: RRMS: 41.4 to 44.0 years; PPMS: 53.7 to 57.5 years; SPMS: 52.8 to 56.6 y
• Prevalence for all MS phenotypes is higher in females. The female:male proportion has remained stable in the RRMS and SPMS groups but has declined in the PPMS group (62.9% to 56.0%; p = 0.05)
• For 2017, the projected number of people effected with MS were approximately 141,000 including ~112K (RRMS), ~8K (PPMS), and ~21K (SPMS)
• Use of DMTs has increased since 2010. Use of interferons has declined for all MS phenotypes in favor of newer DMTs, fingolimod or dimethyl fumarate especially from 2014 onwards
• Use of concomitant medications for symptoms management was higher in SPMS and PPMS vs RPMS: (a) antidepressants use: SPMS (34%) and PPMS (31%) vs RRMS (25%), (b) muscle relaxants use: SPMS (39%) and PPMS (33%) vs RRMS (11%), and (c) antiepileptics, urinary antispasmodics, or medications to manage fatigue – also higher use in SPMS and PPMS compared to RRMS
• Clinical Conditions: Depression was significantly more common in SPMS vs. RRMS. Hypertension and cognitive dysfunction were significantly more common in PPMS or SPMS compared with RRMS
• Pregnancies were reported in females across all cohorts.

CONCLUSIONS

• Prevalence of all MS phenotypes have increased over time.
• The age of MS patients has increased over time, which may be due to a combination of increased incidence, increased prevalence, and/or improved standard of treatment, healthcare, or other factors
• No DMTs were approved for PPMS during the study period, 2010-2017; although, DMTs for RRMS were prescribed (likely off label) for PPMS. Ocrelizumab was approved for PPMS by the EMA in 2018.
• PPMS and SPMS patients were more likely to be prescribed other medications for symptom management, with antidepressants being most common.
• Majority of pregnancies occurred in RRMS group, likely because this population was younger.

IMPLICATIONS

Increased prevalence of MS and increased age of MS patients signals an increasing burden of MS in the public healthcare system and presents new challenges in the treatment of MS.

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Definitions, Notes

Patients were aggregated by calendar year (CY) and the first diagnosis of MS within each CY was termed the index date. Only those MS cases with a specified phenotype are reported.

The prevalence of each MS phenotype was defined as the number of cases per 100,000 and was calculated based on the number of patients with the phenotype of interest over the total number of individuals in the BKK database in each CY.

The number of patients with each MS phenotype was stratified by sex and age (18–29, 30–44, 45–59, and ≥60 years).

Selected muscle relaxants: baclofen, botulinum toxin, dantrolene, tizanidine, tolperisone, tetrazepam

Selected medications to manage fatigue: amantadine, fampridine, modafinil, psychostimulant

Depression being one of the most frequently reported clinical conditions of interest in MS with an incidence of 35–44% across the three MS phenotypes and significantly more common in patients with SPMS versus RRMS.

MS-related spasticity is a frequent problem in advanced MS and is reported in 66–86% of patients.