Health-related quality of life across disease stages in patients with amyotrophic lateral sclerosis: results from a real-world survey

Journal of Neurology (2024) 271:2390–2404 https://doi.org/10.1007/s00415-023-12141-y ORIGINAL COMMUNICATION Health‑related quality of life across disease stages in patients with amyotrophic lateral sclerosis: results from a real‑world survey Katie Stenson1 · T. E. Fecteau1 · L. O’Callaghan1,4 · P. Bryden1 · J. Mellor2 O. Thomas2 · H. Iqbal2 · S. Barlow2 · S. Parvanta3 · J. Wright2 · L. Earl2 · Received: 24 August 2023 / Revised: 28 November 2023 / Accepted: 29 November 2023 / Published online: 11 January 2024 © The Author(s) 2024 Abstract Background Amyotrophic lateral sclerosis (ALS) is characterized by a rapid disease course, with disease severity being associated with declining health-related quality of life (HRQoL) in persons living with ALS (pALS). The main objective of this study was to assess the impact of disease progression on HRQoL across King’s, Milano-Torino Staging (MiToS), and physician-judgement clinical staging. Additionally, we evaluated the impact of the disease on the HRQoL of care partners (cALS). Methods Data were sourced from the Adelphi ALS Disease Specific Programme (DSP)™, a cross-sectional survey of neurologists, pALS and cALS presenting in a real-world clinical setting between July 2020 and March 2021 in Europe and the United States. Results Neurologists (n = 142) provided data for 880 pALS. There were significant negative correlations between all three clinical staging systems and EuroQol (European Quality of Life) Five Dimension Five Level Scale (EQ-5D-5L) utility scores and visual analogue scale (VAS) ratings. Although not all differences were significant, 5-item Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-5) scores showed a stepwise increase in HRQoL impairment at each stage of the disease regardless of the staging system. At later stages, high levels of fatigue and substantial activity impairment were reported. As pALS disease states progressed, cALS also experienced a decline in HRQoL and increased burden. Conclusions Across outcomes, pALS and cALS generally reported worse outcomes at later stages of the disease, highlighting an unmet need in this population for strategies to maximise QoL despite disease progression. Recognition and treatment of symptoms such as pain and fatigue may lead to improved outcomes for pALS and cALS. Keywords Amyotrophic lateral sclerosis · Quality of life · Patient-reported outcomes · Disease progression · Real-world evidence Background Amyotrophic lateral sclerosis (ALS) is a rare, heterogenous, neurodegenerative disease, characterized by progressive loss of muscle function, and ultimately death [1]. ALS is thought to be caused by a combination of genetic and environmental factors [2, 3]. ALS has a median survival of around 3 years * Katie Stenson 1 Biogen, Cambridge, MA, USA 2 Adelphi Real World, Bollington, UK 3 The ALS Association, Arlington, VA, USA 4 Present Address: Sage Therapeutics, Boston, MA, USA Vol:.(1234567890) after symptom onset, with respiratory failure being the cause of death in most cases [1]. The King’s staging and Milano-Torino Staging (MiToS) systems are established clinical staging systems used to monitor ALS disease progression [4]. The King’s system assesses any loss of independence in affected regions (bulbar, lower limb, upper limb) and requirement for assistive devices (gastrostomy and tracheostomy), whereas MiToS assesses complete loss of independence in four key domains (bulbar, gross motor, fine motor, and respiratory function) [4, 5]. The King’s system typically differentiates well in early-stage disease, with MiToS being better in differentiating mid- to late-stages [4, 6]. Both staging criteria are derived or can be mapped from Revised Amyotrophic Lateral Sclerosis Functional Rating (ALSFRS-R) scores [7, 8]. Journal of Neurology (2024) 271:2390–2404 Additionally, persons living with ALS (pALS) can be staged as ‘early’/’mid’/’late’ by leveraging a physician’s treatment experience to outline the current stage of the disease in relation to the expected disease duration for that patient. This physician-judgment staging method is more subjective but is useful when ALSFRS-R scores are not available. Physical impairment and progression rate of physical deterioration in ALS have a significant impact on emotional well-being and there is a correlation between disease severity and/or decreasing physical function and declining healthrelated quality of life (HRQoL) [9, 10]. A recent systematic literature review investigating the burden of ALS confirmed that pALS experienced poor QoL and loss of function, which deteriorated with disease progression [11]. The burden of symptoms was high, with patients experiencing various debilitating symptoms, with fatigue, depression, and pain being the most frequently reported [11]. On the other hand, there are reports in the literature of relatively wellmaintained QoL despite physical function decline [12–14]. Interestingly, Vázquez Medrano and colleagues [15] found that disease progression but not physical state per se determined mental well-being in ALS. Depending on the severity of the disease, care partners of pALS (cALS) who are not providing care under a professional contract may spend most of the day providing care, resulting in substantial humanistic and economic burden, with associated depression and reduced QoL [11, 16]. A cross-sectional survey in Germany revealed that costs of informal care (i.e., care provided by non-professional care partners, mainly family members) represented nearly half of all costs of illness in ALS [17]. pALS and cALS are also less likely to be gainfully employed [18], and this productivity loss may have a significant financial impact on pALS and cALS [18]. While outcome measures such as ALSFRS-R capture changes in physical functioning, tools such as the EuroQol (European Quality of Life) Five Dimension Five Level Scale (EQ-5D-5L) [19] or disease-specific patient-reported outcomes (PRO) measures such as the 40-item Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) and 5-item Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-5), can be utilized to assess well-being and quality of life as perceived by pALS and/or cALS. Although longitudinal studies of QoL in pALS and cALS, using different instruments and varying in focus and conclusions, have been previously conducted [20–24], publications reporting real-world changes in QoL and other disease-specific PRO measures across the ALS disease course remain rare. Hence, the main objective of the present study was to assess the impact of disease progression on HRQoL across King’s, MiToS, and physician-judgement stages. Additionally, we evaluated the care partner burden and the impact of the disease on the HRQoL of cALS. 2391 Methods Data were sourced from the Adelphi ALS Disease Specific Programme (DS)™, a large, prospective, cross-sectional survey of neurologists, pALS and cALS presenting in a realworld cli (...truncated)