Differentiating societal costs of disability worsening in multiple sclerosis



In multiple sclerosis (MS), confirmed disability progression (CDP) can be either the result of progression independent of relapse activity (PIRA) or relapse-associated worsening (RAW). However, the economic effect of PIRA and RAW on societal economic costs in patients with MS is not well understood.


To determine societal economic costs of patients achieving disease activity free status (DAF) and compare them with those having PIRA and RAW events.


We used a roving EDSS score analysis to detect PIRA and RAW events with confirmation after at least 6 months. We estimated the age-, gender-, EDSS-adjusted effects of PIRA and RAW on total, direct medical, direct non-medical and indirect societal economic costs. Patients achieving DAF were assigned to as reference.


Overall, 1959 patients were analyzed. Total mean quarterly societal economic costs including disease-modifying therapies (DMTs) were 6929€ (SD: 2886€) per patient averaged over a period of 2 years. Excluding DMTs, patients achieving DAF had total mean quarterly costs of 1703€ (SD: 2489€). PIRA caused 29% (IRR: 1.29; CI 1.06–1.50, p < 0.05) higher total costs compared to DAF. On the contrary, RAW increased total costs by factor 1.56 (CI 1.30–1.87, p < 0.001). The effect of PIRA and RAW was striking for direct medical costs which increased by factor 1.48 (95% CI 1.13–1.95, p < 0.01) and 2.25 (95% CI 1.72–2.94, p < 0.001), respectively.


Disease progression increases societal economic costs significantly. Thus, delaying or even preventing disease progression in MS may reduce the societal economic burden of MS.

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Author information

Correspondence to Tjalf Ziemssen.

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Conflicts of interest

NHN has received funding for research from Novartis. DS has nothing to disclose. RH has received speaker fee from Sanofi and travel grants from Celgene. BE is an employee of Novartis. CC was an employee of Novartis at the time of this study, and now an employee of Siemens. TZ received personal compensation from Almirall, Biogen, Bayer, Celgene, Novartis, Roche, Sanofi, Teva for consulting and speaking services and he is the section editor for BMC Neurology. Additionally, he received financial support for research activities from BAT, Biogen Novartis, Teva and Sanofi.

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Approval for PANGAEA and PEARL were obtained from independent, local competent ethics committees.

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All patients provided written informed consent for the collection of clinical and health economic information.

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The original version of this article was revised: The captions of figure 2 and figure 3 are mismatched.

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Ness, N., Schriefer, D., Haase, R. et al. Differentiating societal costs of disability worsening in multiple sclerosis. J Neurol (2019).

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  • Multiple sclerosis
  • Progression
  • Worsening
  • Resource utilization
  • Cost of illness