SYSTEMATIC LITERATURE REVIEW OF LIMITATIONS IN THE HYPOTHYROIDISM TREATMENT PARADIGM: CHALLENGES TO STABLE CONTROL AND QUALITY OF LIFE
Author(s)
James Meyer1, Tapan Patel, PharmD2, Katherine Park, MPH3, Devyani Bhatnagar, MS3, Bhagyashree Oak, PhD4, Matthew O'Hara, MBA5;
1Chicago, IL, USA, 2Xeris Pharmaceuticals, Inc., GAITHERSBURG, MD, USA, 3Trinity Life Sciences, Boston, MA, USA, 4Trinity Lifesciences, Billerica, MA, USA, 5Trinity Life Sciences, HINGHAM, MA, USA
1Chicago, IL, USA, 2Xeris Pharmaceuticals, Inc., GAITHERSBURG, MD, USA, 3Trinity Life Sciences, Boston, MA, USA, 4Trinity Lifesciences, Billerica, MA, USA, 5Trinity Life Sciences, HINGHAM, MA, USA
OBJECTIVES: Despite existing hypothyroidism treatments, patients continue to experience persistent symptoms and unmet needs, indicating unstable biochemical control and gaps in management. This systematic literature review (SLR) assessed the burden of hypothyroidism and its impact on quality of life (QoL) in a broader population affected by adherence constraints and levothyroxine (LT4) absorption disorders.
METHODS: This SLR followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist and included English‑language, peer‑reviewed studies in PubMed and Embase from January 2010 to October 2025. An artificial intelligence (AI)-enhanced platform supported screening, with human reviewers screening titles/abstracts in parallel with the AI, and an independent adjudicator resolving discrepancies. Two independent reviewers conducted full-text screening.
RESULTS: Of the 2,911 unique publications identified, non-mutually exclusive subsets were non‑adherence (N=69), LT4 absorption disorders (N=87), and QoL outcomes (N=87). This body of literature reflects the burden of unstable control driven by absorption disorders and adherence constraints. Non-adherence was often linked to the burden of daily LT4 administration. Absorption variability (encompassing a spectrum of LT4 absorption disorders driven by food-drug interactions, gastrointestinal disorders and comorbidities), was frequently associated with unstable thyroxine levels, persistent symptoms, and frequent dose adjustments, suggesting inadequate therapeutic control. Patient-reported outcome measures consistently showed physical, emotional, and cognitive burdens and treatment inconvenience, with burden persisting despite LT4 therapy and titration. This pattern underscores that achieving biochemical targets does not always translate into clinical stability or improved QoL. Alternative formulations or dosing strategies improved adherence and/or bioavailability in select groups, including patients with comorbidities, children, and elderly.
CONCLUSIONS: Unmet needs remain as LT4 absorption challenges, treatment burden, and adherence-related constraints are consistently linked to unstable biochemical control and impaired QoL. More effective and personalized treatment approaches that reduce the impact of absorption variability and the burden of daily administration are needed.
METHODS: This SLR followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist and included English‑language, peer‑reviewed studies in PubMed and Embase from January 2010 to October 2025. An artificial intelligence (AI)-enhanced platform supported screening, with human reviewers screening titles/abstracts in parallel with the AI, and an independent adjudicator resolving discrepancies. Two independent reviewers conducted full-text screening.
RESULTS: Of the 2,911 unique publications identified, non-mutually exclusive subsets were non‑adherence (N=69), LT4 absorption disorders (N=87), and QoL outcomes (N=87). This body of literature reflects the burden of unstable control driven by absorption disorders and adherence constraints. Non-adherence was often linked to the burden of daily LT4 administration. Absorption variability (encompassing a spectrum of LT4 absorption disorders driven by food-drug interactions, gastrointestinal disorders and comorbidities), was frequently associated with unstable thyroxine levels, persistent symptoms, and frequent dose adjustments, suggesting inadequate therapeutic control. Patient-reported outcome measures consistently showed physical, emotional, and cognitive burdens and treatment inconvenience, with burden persisting despite LT4 therapy and titration. This pattern underscores that achieving biochemical targets does not always translate into clinical stability or improved QoL. Alternative formulations or dosing strategies improved adherence and/or bioavailability in select groups, including patients with comorbidities, children, and elderly.
CONCLUSIONS: Unmet needs remain as LT4 absorption challenges, treatment burden, and adherence-related constraints are consistently linked to unstable biochemical control and impaired QoL. More effective and personalized treatment approaches that reduce the impact of absorption variability and the burden of daily administration are needed.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
PCR168
Topic
Patient-Centered Research
Topic Subcategory
Adherence, Persistence, & Compliance, Patient Behavior and Incentives, Patient-reported Outcomes & Quality of Life Outcomes
Disease
SDC: Diabetes/Endocrine/Metabolic Disorders (including obesity)