Long-term treatment risks in multiple sclerosis: risk knowledge and risk perception in a large cohort of mitoxantrone-treated patients.

BACKGROUND: Balancing treatment benefits and risks is part of a shared decision-making process before initiating any treatment in multiple sclerosis (MS). Patients understand, appreciate and profit from evidence-based patient information (EBPI). While these processes are well known, long-term risk awareness and risk processing of patients has not been studied. Mitoxantrone treatment in MS is associated with long-term major potential harms - leukaemia (LK) and cardiotoxicity (CT). The risk knowledge and perception among patients currently or previously treated with mitoxantrone is unknown. OBJECTIVES: The objective of this article is to conduct a retrospective cohort study in greater Hamburg, Germany, to estimate risk awareness and perception in MS patients treated with mitoxantrone. METHODS: MS patients with at least one dose of mitoxantrone between 1991 and 2010 from six major MS centres in greater Hamburg received a questionnaire assessing risk awareness and perception as well as a written EBPI about mitoxantrone-associated LK and CT. RESULTS: Fifty-one per cent in the cohort of n = 575 patients returned the questionnaire. Forty per cent correctly estimated the risk of LK (CT 16%); 56% underestimated the risk (CT 82%). Reading the information increased the accuracy of LK risk estimation, and patients did not report an increase of worries. The EBPI was appreciated and recommended by 85%. CONCLUSION: Risk awareness of mitoxantrone-treated patients is insufficient, but can be increased by EBPI without increasing worries. Continued patient information during and after treatment should be implemented in management algorithms.

Costs and quality of life of multiple sclerosis in Germany.

This cost-of-illness analysis based on information from 2973 patients with multiple sclerosis (MS) in Germany is part of a Europe-wide study on the costs of MS. The objective was to analyze the costs and quality of life (QOL) related to the level of disease severity. Patients from six centres (office- and hospital-based physicians) and patients enrolled in a database were asked to participate in the survey; 38% answered a mail questionnaire. In addition to details on the disease (type of disease, relapses, level of functional disability), the questionnaire asked for information on all resource consumption, medical, non-medical, work absence, informal care, as well as QOL (measured as utility). The mean age of the cohort was 45 years, and 18% of patients were 65 years of age or older. Forty-seven percent of patients had mild disease (Expanded Disability Status Scale [EDSS] score 0-3), 36% had moderate disease (EDSS score 4-6.5) and 12% had severe disease (EDSS score > or =7). The mean EDSS score in the sample was 3.8 (median 4.0), with a mean utility of 0.62. Costs and utility are highly correlated with disease severity. Workforce participation decreases from 73% in very early disease to less than 10% in the very late stages, leading to a tenfold rise in productivity losses in the late stages of disease. Hospitalisation and ambulatory visits rise by a factor of 5-6 between early and late disease; investments and services increase from basically no cost to euro 2700; and informal care increases by a factor of 27 for patients with an EDSS score of 7 and by a factor of 50 for patients at the very severe end of the EDSS scale (8-9). Hence, total mean costs per patient are determined essentially by the distribution of the severity levels in the sample, increasing from approximately euro 18 500 at an EDSS score of 0-1 to euro 70 500 at an EDSS score of 8-9. The same is true for utility, which decreases from 0.86 to 0.10 as the disease becomes severe. However, the utility loss compared to the general population is high at all levels of the disease, leading to an estimated loss of 0.2 quality-adjusted life-years per patient. Relapses are associated with a cost of approximately euro 3 000 and a utility loss of 0.1 during the quarter in which they occur. Compared with a similar study performed in 1999, resource consumption, with the exception of drugs, is somewhat lower. This is most likely due to a difference in the severity distribution of the two samples and to changes in health-care consumption overall in the country, such as the introduction of diagnosis-related groups (DRGs, Fallpauschalen).

Escalating immunotherapy of multiple sclerosis--new aspects and practical application.

Recent clinical studies in multiple sclerosis (MS) provide new data on the treatment of clinically isolated syndromes, on secondary progression, on direct comparison of immunomodulatory treatments and on dosing issues. All these studies have important implications for the optimized care of MS patients. The multiple sclerosis therapy consensus group (MSTCG) critically evaluated the available data and provides recommendations for the application of immunoprophylactic therapies. Initiation of treatment after the first relapse may be indicated if there is clear evidence on MRI for subclinical dissemination of disease. Recent trials show that the efficacy of interferon beta treatment is more likely if patients in the secondary progressive phase of the disease still have superimposed bouts or other indicators of inflammatory disease activity than without having them. There are now data available, which suggest a possible dose-effect relation for recombinant beta-interferons. These studies have to be interpreted with caution, as some potentially important issues in the design of these studies (e. g. maintenance of blinding in the clinical part of the study) were not adequately addressed. A meta-analysis of selected interferon trials has been published challenging the value of recombinant IFN beta in MS. The pitfalls of that report are discussed in the present review as are other issues relevant to treatment including the new definition of MS, the problem of treatment failure and the impact of cost-effectiveness analyses. The MSTCG panel recommends that the new diagnostic criteria proposed by McDonald et al. should be applied if immunoprophylactic treatment is being considered. The use of standardized clinical documentation is now generally proposed to facilitate the systematic evaluation of individual patients over time and to allow retrospective evaluations in different patient cohorts. This in turn may help in formulating recommendations for the application of innovative products to patients and to health care providers. Moreover, in long-term treated patients, secondary treatment failure should be identified by pre-planned follow-up examinations, and other treatment options should then be considered.