Symptom variability and treatment response in pernicious anaemia: a longitudinal daily symptom tracking study
- 1University College London
Abstract
Pernicious Anaemia is an autoimmune-mediated disorder of vitamin B12 absorption, managed using fixed-interval vitamin B12 replacement regimens. Despite treatment, many patients report persistent or recurrent symptoms, suggesting substantial inter-individual variability in treatment response. More tailored approaches may therefore be needed to reduce symptom burden and improve quality of life. This prospective observational study used high-frequency longitudinal digital symptom monitoring to characterise symptom dynamics and heterogeneity in treatment response. UK adults with pernicious anaemia, recruited via the Pernicious Anaemia Society, self-reported daily symptoms (severity 0-10) and vitamin B12 treatments over three months. Analyses quantified within- and between-person variability, injection-aligned symptom response kinetics, and differences in treatment response by injection frequency. Sixty-eight participants were included in the longitudinal analyses, providing >5,100 person-days of symptom data over a mean of 76 days (SD 28). Most symptom variance was attributable to stable between-person differences (ICC range, 0.58-0.80), indicating the persistence of individual symptom phenotypes. Vitamin B12 injections were followed by rapid symptom improvement, although magnitude and timing varied markedly by symptom domain. Seventy-one percent of participants were classified as responders for composite symptom burden (median 4.65 to 2.36; p<0.001), while 29% showed no meaningful multisystem improvement (3.59 to 3.58; p=0.63). Cognitive symptoms improved earliest, typically within 24-72 hours; fatigue and pain responses peaked at 3-5 days, and neuro-sensory symptoms at 4-6 days. Responses clustered within individuals, indicating distinct responder phenotypes. Overall symptom burden improved most among participants receiving monthly injections, whereas those injecting weekly or more often had higher pre-injection burden and smaller improvements. These findings suggest that fixed-interval vitamin B12 replacement may not adequately reflect individual variation in symptom recurrence and treatment response. High-frequency digital symptom monitoring may provide a practical framework for characterising these patterns and for evaluating more individualised, symptom-guided vitamin B12 management.
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BibTeX
@misc{thain2026symptom,
title = {{Symptom variability and treatment response in pernicious anaemia: a longitudinal daily symptom tracking study}},
author = {A. Thain and K. Hart and K. Burchell and P. Visser and K. R. Ahmadi},
howpublished = {medRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.03.26367157},
url = {https://www.medrxiv.org/content/10.64898/2026.11.03.26367157v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Symptom variability and treatment response in pernicious anaemia: a longitudinal daily symptom tracking study
AU - A. Thain
AU - K. Hart
AU - K. Burchell
AU - P. Visser
AU - K. R. Ahmadi
PY - 2026
DA - 2026/11/03
PB - medRxiv
DO - 10.64898/2026.11.03.26367157
UR - https://www.medrxiv.org/content/10.64898/2026.11.03.26367157v1
AB - Pernicious Anaemia is an autoimmune-mediated disorder of vitamin B12 absorption, managed using fixed-interval vitamin B12 replacement regimens. Despite treatment, many patients report persistent or recurrent symptoms, suggesting substantial inter-individual variability in treatment response. More tailored approaches may therefore be needed to reduce symptom burden and improve quality of life. This prospective observational study used high-frequency longitudinal digital symptom monitoring to characterise symptom dynamics and heterogeneity in treatment response. UK adults with pernicious anaemia, recruited via the Pernicious Anaemia Society, self-reported daily symptoms (severity 0-10) and vitamin B12 treatments over three months. Analyses quantified within- and between-person variability, injection-aligned symptom response kinetics, and differences in treatment response by injection frequency. Sixty-eight participants were included in the longitudinal analyses, providing >5,100 person-days of symptom data over a mean of 76 days (SD 28). Most symptom variance was attributable to stable between-person differences (ICC range, 0.58-0.80), indicating the persistence of individual symptom phenotypes. Vitamin B12 injections were followed by rapid symptom improvement, although magnitude and timing varied markedly by symptom domain. Seventy-one percent of participants were classified as responders for composite symptom burden (median 4.65 to 2.36; p<0.001), while 29% showed no meaningful multisystem improvement (3.59 to 3.58; p=0.63). Cognitive symptoms improved earliest, typically within 24-72 hours; fatigue and pain responses peaked at 3-5 days, and neuro-sensory symptoms at 4-6 days. Responses clustered within individuals, indicating distinct responder phenotypes. Overall symptom burden improved most among participants receiving monthly injections, whereas those injecting weekly or more often had higher pre-injection burden and smaller improvements. These findings suggest that fixed-interval vitamin B12 replacement may not adequately reflect individual variation in symptom recurrence and treatment response. High-frequency digital symptom monitoring may provide a practical framework for characterising these patterns and for evaluating more individualised, symptom-guided vitamin B12 management.
ER -