Medication adherence, persistence, switching and dose escalation with the use of tumor necrosis factor (TNF) inhibitors among Texas Medicaid patients diagnosed with rheumatoid arthritis
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The main purpose of this study was to evaluate medication use patterns (i.e., dose escalation, medication adherence, persistence, and switching) of rheumatoid arthritis (RA) patients on etanercept (ETN), infliximab (IFX) or adalimumab (ADA) and the associated healthcare utilization costs using Texas Medicaid data. Study participants were Medicaid beneficiaries (18-63 years) with an RA diagnosis (ICD-9-CM code 714.0x) who had no claim for a biologic agent in the 6-month pre-index period (July 1, 2003 - Dec 31, 2010). The index date was the first date when the patient had the first fill for any of the study TNF inhibitors (ETN, ADA or IFX) within the study identification period (Jan 1, 2004 – Aug 31, 2010). Data were extracted from July 1, 2003 to August 31, 2011. Prescription and medical claims were analyzed over an 18-month study period (i.e., 6-month pre-index and 12-month post-index periods). The primary study outcomes were adherence, persistence, dose escalation, switching and cost (i.e., total healthcare, RA-related and TNF inhibitor therapy cost). The study covariates were demographic factors (age, gender, race/ethnicity), pre-index use of other RA-related medications (pain, glucocorticoids and disease modifying antirheumatic drugs), total number of non-study RA-related medications used at index, pre-index RA and non-RA related visits, pre-index healthcare utilization cost and Charlson Comorbidity Index score. Conditional regression analyses, which accounts for matched samples, were used to address the study objectives. After propensity score matching, 822 patients (n=274/group) comprised the final sample. The mean age (±SD) was 48.9(±9.8) years, and the majority of the subjects were between 45 and 63 years (69.2%), Hispanic (53.7%) and female (88.0%). Compared to patients on ETN, the odds of having a dose escalation were ≈ 5 [Odds Ratio= 4.605 [95% CI= 1.605-12.677], p=0.0031] and ≈ 8 [Odds Ratio=7.520, [95% CI= 2.461-22.983], p=0.0004] times higher for IFX and ADA patients, respectively, while controlling for other variables in the model. Compared to ETN, patients on IFX (p=0.0171) were more adherent while adherence was comparable with patients on ADA (p=0.1144). Compared to patients on ETN, the odds of being adherent (MPR ≥ 80%) to IFX was ≈ 2 times higher [Odds Ratio= 2.437, [95% CI=1.592-3.731], p < 0.0001] while controlling for other variables in the model. Persistence to index TNF inhibitor therapy and likelihood to switch or discontinue index TNF inhibitor therapy were comparable among the 3 study groups. In addition, the duration of medication use (i.e., persistence) prior to switching or discontinuation of index therapy was comparable among the 3 study groups. Furthermore, for each of the cost variables (total healthcare, RA-related and TNF inhibitor therapy cost), costs incurred by patients on ETN were significantly lower (p < 0.01) than those incurred by ADA patients but significantly higher (p < 0.01) than those incurred by IFX patients. Finally, a positive and significant relationship (p < 0.0001) was found between RA-related healthcare cost, adherence and persistence to TNF inhibitor therapies. In conclusion, ETN was associated with lower rates of dose escalation compared to ADA or IFX. However, adherence was better and associated healthcare costs were lower with IFX. Clinicians should endeavor to work with each individual patient to identify patient-specific factors responsible for poor medication use behaviors with TNF-inhibitor therapies. Reducing the impact of these factors and improving adherence should be included as a major part of the treatment plan for each RA patient. RA patients need to be adequately educated on the importance of adhering and persisting to their TNF-inhibitor therapy as poor medication adherence/persistence negatively impacts the RA disease process.