Treating MS-Fatigue with the Digital Therapeutic Elevida: Further Analyses from a Randomized Controlled Trial and First-Year Routine Care Experiences

Background: Fatigue affects up to 70% of patients with multiple sclerosis (PwMS), is often experienced as the most disabling problem, and is linked with depression, cognitive impairment and early retirement. Unfortunately, treatment options for MS-fatigue are limited, as meta-analyses have suggested that pharmacological treatment may be ineffective, and cognitive behavioral therapy (CBT), although promising, is rarely available to many patients due to a shortage of trained therapists and other barriers, such as mobility impairments, cost, cognitive impairment, or the fatigue itself. CBT-based digital therapy programs (digital therapeutics) could improve the quality of treatment for MS-fatigue because they can be delivered flexibly and at low cost to large numbers of patients via the Internet. We have developed the CBT-based digital therapeutic ‘elevida’, which has been shown to be effective in a randomized controlled trial with n=275 patients, in terms of reducing MS-fatigue over the course of 12 and up to 24 weeks.

Objectives: To describe the process by which elevida gained governmental approval for general reimbursement in Germany, and to report on the first year of experiences after this digital therapeutic has become widely available in the German healthcare system.

Methods: To gain approval for general reimbursement in Germany (72 million patients covered under universal healthcare), further sensitivity analyses had been requested to confirm the robustness of trial results. Therefore, we re-analyzed data from the elevida trial by using more conservative reference-based multiple imputation procedures, such as jump-to-reference, which assume that drop-outs follow symptom trajectories similar to those in the control group.

Results: The sensitivity analyses confirmed the presence of robust treatment effects (d = 0.30 - 0.39, ps < 0.02). Even under the assumption that drop-outs experienced substantially worse symptom courses than non-drop-outs, it could be confirmed that elevida led to significant and clinically relevant reductions in MS-fatigue over 12 and up to 24 weeks.

Conclusions: Based on these findings and after a thorough review by the German Federal Institute for Drugs and Medical Devices, elevida has become the first digital therapeutic for MS to be included permanently in the German government’s directory of reimbursable digital health applications, the “DiGA Verzeichnis”. We are reporting here on the first year of experiences in this context, focusing on facilitators and barriers to implementation of elevida in the German healthcare system.