Introduction: Treatment of multiple sclerosis (MS) has developed significantly and several new immunotherapeutic drugs have become available in Finland since 2004. We studied whether this is associated with changes in hospital admission frequencies and healthcare costs and whether admission rates due to infection have increased.
Methods: The national Care Register for Health Care was searched for all discharges from neurological, medical, surgical, neurosurgical and intensive care units with MS as a primary diagnosis or an auxiliary diagnosis for primary infection diagnosis in 2004–2014. Only patients 16 years of age were included.
Results: We identified 12,276 hospital admissions for 4296 individuals. The number of admissions declined by 4.6% annually (p..0024) in both genders. Proportion of admissions with an infection as the primary diagnosis increased but no change in their frequency was found. They were longer than admissions with MS as the primary diagnosis and were associated with increased in-hospital mortality. The annual aggregate cost of hospital admissions declined by 51% during the study period.
Conclusions: This study shows that hospital admission rates and costs related to MS hospital admissions have markedly declined from 2004 to 2014 in Finland, which coincides with an increase in the use of disease-modifying therapies.
Hospital admission rates and costs related to MS hospital admissions have markedly declined from 2004 to 2014 in Finland.
Proportion of admission related to infection has increased and they are associated with longer hospitalizations and increased in-hospital mortality pointing out the importance of infection prevention.
Multiple sclerosis (MS) is the most common neurological disorder which causes disability in young adults. It is a chronic autoimmune disease in which immune cells destroy central nervous system (CNS) myelin. In most patients, MS is at first relapsingremitting but becomes progressive over time. There is no cure for MS, but therapies affecting the immune system can reduce disease activity and progression of disease in relapsing forms of MS. Like the other Nordic countries Finland belongs to a high-risk area of MS. Incidence and prevalence are increasing and there are marked regional differences such that the disease is most common both in western and southwestern Finland [1–4 ].
Treatment of MS has developed significantly since the era of the first injectable therapies became available more than 20 years ago. Several new diseasemodifying therapies (DMT’ s) have been introduced since 2004: natalizumab, fingolimod, teriflunomide, dimethyl fumarate, alemtuzumab, peginterferon b -1a, daclizumab, cladribine and ocrelizumab [5–12 ]. The superior therapeutic efficacy of the monoclonal antibody therapies and daclizumab has been demonstrated in phase 3 trials by comparing them against the older platform injectable therapies, or by large-scale real-world data bases [6 ,8 ,10 ,11 ]. It has been established that the earlier the DMT’ s are used, the better their efficacy is in reducing relapses [11 ]. However, there is less evidence of DMT’ s preventing disease progression. Prevention of progression to severe disability could lead to reduced need for e.g. intrathecal baclofen pumps for severe spasticity. On the other hand, the most potent immunosuppressive therapies bear higher risk for adverse events such as opportunistic infections [12 ]. Emergence of secondary autoimmune diseases has also been observed in patients treated with alemtuzumab, and fingolimod therapy has been associated with an increased risk of cardiac and eye complications [6 ,13 ].
Hospital admissions use a significant amount of healthcare resources. Hospital admission rates in MS patients are higher than in the general population despite a dramatic decrease observed over the past 25 years [14 ]. In addition to MS relapses severe enough to necessitate hospital admission, a proportion of this raised risk of hospitalization may be due to surveillance bias as patients are being monitored regularly by outpatient clinic. MS patients have been shown to be at an increased hospital admission risk for infections [15 ]. The purpose of this study was to evaluate recent trends in MS hospital admission rates and the role of infections in MS-related hospital admissions in all Finnish hospitals. We wanted to find out whether disease- modifying drugs have affected hospital admission rates and whether admission rates due to infection have increased. Our hypothesis was that admission rates would have decreased but admissions related to infections could have increased. To answer these questions, we did a retrospective database search to investigate hospital admissions related to MS, and admissions with an infection as a primary diagnosis and MS as an auxiliary diagnosis, from 2004 to 2014 using administrative public health care hospital discharge data. We will discuss hospitalization trends and costs in relation to the changes in the use and costs of MS DMTs during the same time in Finland.
Material and methods
The Care Register for Health Care (CRHC), a mandatory database maintained by National Institute for Health and Welfare (THL) for all public health care hospital discharges in Finland, was searched for all discharges from neurological, medical, surgical, neurosurgical and intensive care units with MS (ICD-10 code G35) as a primary diagnosis or an auxiliary diagnosis for primary infection diagnosis between 1 January 2004 and 31 December 2014. The search included all five university hospitals and 39 other hospitals on mainland Finland. Only patients 16 years of age were included. The data on intensive care admission counts proved insufficient for analysis. The Diagnosis Related Group (NordDRG categorization) daily cost of MS hospital care was extracted from THL statistical reports for 2006 (343.35 e /day) and 2011 (473.91 e /day) [16 ,17 ]. The mean of these figures (408.63 e /day) was used for economic calculations in this study. Drug reimbursement data was obtained from the statistics of the Social Insurance Institution of Finland (KELA). The study was approved by the Turku University Hospital Clinical Research Center (Turku CRC) and the National Institute for Health and Welfare of Finland (permissions no.: THL/143/5.05.00/2015 and THL/1349/5.05.00/2015).
Shapiro– Wilk and Kolmogorov– Smirnov tests were used to assess the distribution of continuous variables and, subsequently, the Mann– Whitney U -test or independent samples of the Kruskall– Wallis test were used as appropriate to analyze patient characteristics. Poisson regression was used for analysis of count data, Cox regression was used for in-hospital mortality analysis and linear regression was used for analysis of length of stay (LOS) (log transformed due to skewness) and admission costs. Trend analysis were age and sex adjusted except for admission cost analysis (sex- and age-specific data was not available). Results of univariate analyses were comparable to multivariate models. When analysing differences in LOS, generalized estimating equations (GEE) to accompany repeated admissions from individual subjects were used. Statistical significance was considered to be presented by a p value < .05. Analyses were conducted using SAS System for Windows, version 9.4 (SAS Institute Inc., Cary, NC) or IBM SPSS Statistics for Windows, Version 24.0 (IBM Corp., Armonk, NY).