Impact of treatment burden on medication adherence and quality of life in amyotrophic lateral sclerosis: a prospective multicentre study

BACKGROUND: Patients with amyotrophic lateral sclerosis (ALS) face substantial barriers to medication adherence as disease progression necessitates complex drug formulation adjustments, such as crushing tablets, mixing with liquids, or delivering via feeding tubes. These modifications may not only increase the time and effort required but could also impact drug efficacy and safety. OBJECTIVE: To evaluate the prevalence and the impact of treatment burden on medication adherence and patient-reported quality of life (QoL) in ALS. METHODS: This prospective multicenter study enrolled ALS patients across three Italian reference centers, with assessments at baseline, 6, and 12 months. Key measures included the Multimorbidity Treatment Burden Questionnaire (MTBQ), ALSFRS-R, DYALS (dysphagia), Morisky Medication Adherence Scale, SSS-8 (somatic symptoms), INQoL (QoL), SWAMECO (swallowing/medication difficulties), alongside comorbidities and current therapies. Associations between treatment burden, QoL, and adherence were analyzed using multivariable models. RESULTS: A total of 114 consecutive ALS patients were enrolled. Clinically significant treatment burden was observed in 69.3% of patients, with over half reporting moderate-to-high levels according to the MTBQ classification. Elevated burden was independently related to greater somatic symptom severity and formulation modification needs. Moreover, higher burden associated with poorer QoL and diminished adherence after confounder adjustment. Longitudinally, patients experiencing worsening burden over 1 year showed accelerated QoL decline compared to those remaining stable, though adherence trajectories were unaffected. CONCLUSION: Treatment burden, particularly driven by drug formulation complexities and somatic symptoms, emerges as a pivotal, modifiable determinant of adherence and QoL in ALS. Targeted interventions to alleviate modifiable burden components hold promise for optimizing clinical outcomes and enhancing patient-centred care.