Qualitative interviews exploring the patient experience of fatigue in individuals with sickle cell disease (SCD), thalassemia, and pyruvate kinase (PK) deficiency

Abstract Introduction: Hereditary hemolytic anemias (HHAs), including sickle cell disease (SCD), thalassemia, and pyruvate kinase (PK) deficiency, are a group of rare inherited hematological disorders that impair proper function of red blood cells, leading to a wide range of symptoms, clinical complications, and reduced health-related quality of life (HRQoL). The Red Cell Revolution™ (RCR) is an advisory council supported by Agios Pharmaceuticals, made up of members from the SCD, thalassemia, and PK deficiency communities, including patients, caregivers, advocates, Agios representatives, and specialist clinicians. An RCR initiative on unmet research needs in SCD, thalassemia, and PK deficiency identified physical and emotional fatigue as key factors affecting HRQoL that require greater understanding. Fatigue is a complex symptom across these HHAs with far-reaching impacts that are poorly understood. We present interim results from a qualitative study evaluating the experience of fatigue in patients with these respective HHAs. Methods: Participants were aged ≥18 years (yrs), lived in the USA, with a clinician-confirmed diagnosis of SCD, thalassemia, or PK deficiency. An institutional review board-approved, semi-structured interview guide was developed collaboratively. Participants were interviewed about their experiences of disease-related fatigue—specifically, physical, mental, and emotional fatigue—and asked to rate the most bothersome impacts of fatigue. Interviews were conducted virtually and lasted ~45 minutes. Transcripts were analyzed in ATLAS.ti using content analysis for concept elicitation. Results: The interim sample (N=46: n=20 SCD; n=6 α- and n=7 β-thalassemia; n=13 PK deficiency) had a median (range) age of 43.0 yrs (19–74), diverse racial/ethnic backgrounds (43% Black or African American [n=20], 37% White [n=17]), 80% female (n=37), and 48% had completed higher education (n=22). Median (range) number of yrs since HHA diagnosis was 42.0 (8–60), and participants received a median (range) of 2.5 (0–44) blood transfusions in the previous 52 weeks. All participants reported experiencing fatigue, generally described as tiredness and low energy that could not be resolved with sleep or rest. Participants were able to distinguish between physical, mental, and emotional fatigue; however, words such as “exhausted” and “drained”overlapped across fatigue types. Physical fatigue was reported as a bodily experience of “low energy” or feeling “heavy/weak”, similar to general fatigue. Mental fatigue was described as cognitive impairment resulting in “brain fog” or feeling “drained”, leading to difficulty initiating, engaging with, and focusing on tasks. Emotional fatigue was reported as feeling depressed or irritable because of physical/mental fatigue, and the emotional toll of being unable to function like individuals without fatigue. The negative impacts of fatigue were pervasive: Of 46 participants, allreported impacts on daily activities (eg, chores, errands, self-care); 43 reported impacts on physical functioning (eg, exercise, mobility), relationships and social life (eg, activities/events), and sleep (eg, difficulty falling asleep, staying awake in the day); 42 reported impacts on work (eg, missing work, task performance); 41 reported impacts on cognition (eg, memory, concentration); 37 reported impacts on emotions (eg, sadness/depression, anxiety, anger); 33 reported impacts on hobbies (eg, traveling, reading); and 5 reported impacts on education (eg, missed education). Participants ranked cognitive problems as the most bothersome impact of fatigue, followed by impact on relationships and social life.Conclusion: Patients with SCD, thalassemia, and PK deficiency recognized and reported physical, mental, and emotional manifestations of fatigue; the cognitive impacts of fatigue were considered the most bothersome across all groups.The final analysis aims to include 20 participants from each HHA group to better understand key differences and similarities in experiences of fatigue among the three HHAs and across age groups. A single conceptual model will be created, depicting the experience of fatigue across SCD, thalassemia, and PK deficiency, which can be used to identify and assess different aspects of disease-related fatigue among these patients. In turn, this model can be used to help patients, caregivers, and clinicians address the unmet needs of fatigue burden in the overall disease management of HHAs.