Study: No Evidence to Suggest Biologic Dosing Outliers Have Better Clinical Outcomes in RA Patients

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Study assessed the patterns of care for biologic-dosing outliers and nonoutliers in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is an incurable lifelong disorder and biologic medications are often used to reach disease remission or to reduce the disease activity in patients. The majority of biologic medications for RA have recommended fixed dosing; however, effective dosing varies among real-world patients since certain patients can receive higher (high-dose outliers) or lower (low-dose outliers) doses than the fixed recommendation.

The Journal of Managed Care & Specialty Pharmacy published a study to assess the patterns of care for biologic-dosing outliers and nonoutliers in RA patients. All of the subjects were recently initiated on adalimumab (ADA), etanercept (ETN), or infliximab (IFX) as index biologic therapy between July 1, 2006, and February 28, 2014. A patient was considered an outlier if he or she had received at least 1 dose that was less than 90% or greater than 110% of the approved dose on the package. Patient profiles and treatment outcomes of patients considered dosing outliers were compared with the nonoutlier patients.


“It is important to assess the patterns of care in patients who were dosing outliers in order to understand the patient and clinical factors that contribute to patients becoming dosing outliers and how being an outlier affects clinical outcomes and costs,” the authors wrote.

Of the 434 patients included in the study, approximately 10% of the patients were outliers between both, the 1-year and 2-year follow-up cohorts. During the 1-year follow-up, the ADA group had the greatest proportion of high-dose outliers (31%), the IFX group had the highest proportion of low-dose outliers (20%), and the ETN group had the highest proportion of nonoutliers (95%).

During the 2-year follow-up, the ADA groups had the highest proportion of high-dose outliers again (41%), while the IFX group had the highest rate of low-dose outliers with 11%, and the ETN group had the most non-outliers with 83%.

“High-dose outliers are particularly concerning, since they had high expenditures but no evidence of substantial gains in clinical improvement,” the authors concluded. “Before initiating outlier biologic dosing, health care providers may better serve their RA patients by prescribing alternate [disease-modifying antirheumatic drugs] therapies.”

The study calculated that 1 in 10 of the RA study patients were outliers; however, there were no significant benefits found for higher or lower doses of biologics. The researchers called for more studies to further investigate the effects of biologic-dosing outliers on economic, clinical, and patient-reported outcomes.