Decisions on multiple sclerosis immunotherapy: New treatment complexities urge patient engagement

Abstract

For patients with multiple sclerosis (MS) involvement in treatment decisions becomes ever more imperative. Recently new therapeutic options have become available for the treatment of MS and more will be licensed in the near future. Although more efficacious and easier to administer, the new drugs pose increased risks of severe side effects. Also, new diagnostic criteria lead to more and earlier MS diagnoses. Facing increasingly complex decisions, patients need up-to-date evidence-based information and decision support systems in order to make informed decision together with physicians based on their autonomy preferences. This article summarizes recently terminated and ongoing trials on MS patient education and decision aids conducted by the authors' study groups. Programs on relapse management, immunotherapy, and for patients with suspected and early MS have been developed and evaluated in randomized controlled clinical trials. It could be shown that the programs successfully increase knowledge and allow patients to make informed decisions based on their preferences. For the near future, we aim to develop a modular program for all relevant decisions in MS to increase patients' self-management and empower patients to develop their individual approach with the disease. Faced by a disease with many uncertainties, this should enhance patients' sense of control. Still, it remains a challenge to adequately assess decision quality. Therefore, a study in six European and one Australian centers will start soon aiming to establish adequate tools to assess decision-making quality.

Introduction

In 2009 it became clear that the incidence of progressive multifocal leucoencephalopathy (PML), a severe complication of natalizumab treatment, is 1:1000 in multiple sclerosis (MS) patients treated for 2 or more years [1]. Since natalizumab is highly effective in patients with active relapsing MS, decisions about its use are among the most difficult in neurology. Such decisions are paradigmatic for a shared decision-making (SDM) approach [2]. While every effort is made to monitor the risk of natalizumab treatment and to improve PML outcomes, it is ultimately the patient who takes the risk. The situation is further complicated by its fluidity. As data on patients treated for longer periods (i.e. over 3 years) become available, it is possible that the risk increases further and the drug is withdrawn from the market. Moreover the ultimate decision will depend not only on the effectiveness of natalizumab and PML incidence but also on PML outcomes. Guidelines on natalizumab treatment emphasize the need for continuing availability of information and periodic renewal of consent [3].

In the near future, complexity of treatment decisions will further increase as new drugs become available. Fingolimod and cladribine [4], [5] are two oral drugs in the licensing process. Both drugs are promising in terms of efficacy and ease of administration, but potentially more risky than interferons and glatiramer acetate.

Shared decision making (SDM) is an ethical requirement: Within such a partnership, both physicians and patients have responsibilities as recently reasserted by the UK General Medical Council [6]. Above this, effectiveness of SDM interventions has repeatedly been shown. A recent systematic review [7] showed that decision support techniques for people facing health treatments or screening decisions, consistently produced increased knowledge and satisfaction, and optimized health care utilization, but data on health status were inconsistent. However, based on the concept that health is more the ability of an individual to adapt than a defined state [8], we do believe that providing information increases options for adaptation and therefore also for health.

On one hand information on MS is abundantly available while only few sources can be considered reliable or accurate. On the other hand patients keep claiming information needs and their desire for greater understanding is expressed not only by patients who want a leading role in medical decisions, but also by those who prefer a doctor-led approach [9]. Providing patient information is a complex health care intervention, with information structured and presented in variable formats; nevertheless such interventions can be assessed for content validity and replicability, and for effectiveness. In 2000 the UK Medical Research Council produced a guidance which was revised in 2008 providing clear indication on how to develop and evaluate complex interventions which can be applied to the development and testing of evidence-based patient information (EBPI) aids [10]. In parallel the CONSORT statement has recently been extended to randomized controlled trials (RCTs) of nonpharmacological interventions, giving advise on how to report results of such trials [11]. Complex intervention trials are challenging for several reasons, but in particular because of the limited number of suitable outcome measures. This is the case for questionnaires assessing MS knowledge and risk knowledge, where the two recently published instruments are notable exceptions [12], [13]. Previous work showed that risk knowledge in German MS patients was poor and that EBPI increased risk literacy [13], [14]. Another study found that early information about such a sensible issue as possible cognitive dysfunction was appreciated by MS patients [15].

This paper summarizes recently terminated and ongoing RCTs on MS patient information and education aids and gives an overview on an upcoming study.