Introduction: Clinical guidelines recommend levothyroxine as the standard of care for hypothyroidism and that patients should be treated with a consistent preparation of synthetic levothyroxine without switching among formulations. This study examines the likelihoods of negative clinical outcomes between continuous users of Synthroid® (AbbVie, Inc.) and patients who switch from Synthroid® to an alternative formulation of levothyroxine.
Methods: This retrospective cohort analysis utilized data from Optum Clinformatics™ DataMart covering May 1, 2000 to March 30, 2016. After 6 months of consistent use of Synthroid®, patients were categorized as continuous users or as switchers (by filling a prescription for an alternative formulation). Key outcomes included the likelihood of a thyroid-stimulating hormone (TSH) laboratory value out of a guideline recommended range and/or an adverse clinical composite endpoint identified by ICD codes in the patient's claims data over the following 2 years for any of the following: chronic kidney disease, depression, fatigue, heart failure, hyperlipidemia, hypertension, or obesity. Individual components of the composite endpoint were also examined. Outcomes were analyzed using multivariable logistic models on propensity score matched cohorts. Analyses controlled for patient characteristics using SAS 9.4 software. Chi-square and t tests were employed and P < 0.05 was pre-specified as statistically significant.
Results: Propensity score matching resulted in a sample of 9925 continuous users and 9925 switchers. Switchers were significantly more likely than continuers to have a TSH laboratory value out-of-range in the post-period [odds ratio (OR) 1.15; 95% confidence interval (CI) (1.08-1.23)]. Switchers were also more likely to have the composite clinical endpoint [OR 1.23; CI (1.12-1.37)] and to have individual diagnoses of chronic kidney disease, depression, fatigue, hypertension, or obesity in the post-period.
Conclusions: Results of this large retrospective study over an extended time horizon support clinical guideline recommendations that switching among alternative formulations of synthetic levothyroxine should generally be avoided. Continuous use of Synthroid® was associated with a significantly higher likelihood of maintaining the TSH laboratory value within a guideline recommended range and a significantly lower likelihood of being diagnosed with adverse clinical outcomes.
Keywords: Clinical outcomes; Hypothyroidism; Levothyroxine; Switching; Synthroid®; Thyroid-stimulating hormone.