Tapering, Withdrawal of Anti-TNFs Associated With Lower Costs, Worse Disease Control

Treatment strategies involving anti-tumor necrosis factor (anti-TNF) dose tapering or withdrawal among rheumatoid arthritis (RA) patients who are achieving disease control are gaining popularity. Such strategies seek to optimize benefits versus risks with respect to both patient preferences and the high costs of biologic treatments. A 2015 consensus statement from the Spanish Rheumatology Society and Hospital Pharmacy Society advised that, while patients with RA usually relapse after a complete withdrawal of anti-TNF medication, a careful dose tapering of anti-TNF medications can be undertaken in most patients with RA.

A recent study examined the clinical and cost impacts of withdrawal, tapering, or maintenance of anti-TNFs among RA patients in remission, defined as those patients who have a 28-joint Disease Activity Score (DAS28) under 2.6, or patients who have achieved low disease activity (LDA), defined as those who have a DAS28 of less than 3.2.

Researchers, led by Daniel Aletaha, MD, MSc, concluded that tapering or withdrawing anti-TNF medications in RA patients results in reduced healthcare costs, but also results in less time in sustained disease control compared to maintaining anti-TNF therapy. Their analysis is published in the July 2017 issue of ClinicoEconomics and Outcomes Research.

The study focused on the anti-TNFs adalimumab, etanercept, and infliximab, and used a 5-year Markov model with 1-month cycle length that assessed the time to loss of disease control, time to regaining control after treatment reinitiation, and associated medical and anti-TNF costs. It analyzed 14 studies, involving over 2300 patients, using 1 of the 3 anti-TNF agents and adjusted for treatment strategy, anti-TNF, patient type (ie, early or established RA), and model entry criterion (ie, remission or LDA). Total costs for the months spent in each health state were calculated for 4 combinations of scenarios: early or established RA and patients entering the model with remission or LDA. The costs of disease for patients in remission and flare were obtained from a 2011 Spanish study.

Patients whose anti-TNF treatments were withdrawn incurred the lowest overall 5-year healthcare costs, followed by patients whose doses were tapered or maintained; however, withdrawal costs were only marginally lower than tapering costs. Established RA patients had higher total costs than did early RA patients across all treatment strategies. Adalimumab was associated with the lowest costs in the withdrawal and tapering strategies, but the highest costs in the maintenance strategy. The proportion of total costs due to anti-TNFs was similar across the 3 drugs, but was lowest for withdrawal and highest for maintenance.

The adjusted risk of losing disease control upon dose tapering or with maintenance of anti-TNFs was less than half the risk presented by treatment withdrawal, and patients with established RA had a significantly higher risk of losing disease control than did patients with early RA. “Further, risk of losing disease control with [etanercept] was found to be significantly higher than [adalimumab], irrespective of treatment strategy,” the authors state. Thus, the withdrawal strategy was associated with the fewest number of months until loss of disease control, followed by the tapering and maintenance strategies, respectively. Established RA patients had fewer months until loss of disease control than early RA patients, and patients taking adalimumab had a longer time to loss of disease control than those taking etanercept or infliximab.

The researchers conclude that patients whose anti-TNF treatments were withdrawn or tapered incurred lower 5-year healthcare costs, but had worse clinical outcomes than patients who maintained their treatment. The marginally lower costs incurred by withdrawal compared to tapering were offset by substantially less time to loss of disease control.

The researchers note that their model represents the perspective of the healthcare payer, and includes only direct costs, not indirect productivity costs; thus, the true cost of loss of disease control may be greater than shown in the study’s results. The findings also suggest a higher feasibility of withdrawing or tapering anti-TNFs in early RA patients compared to established RA patients. Nevertheless, the researchers conclude that the risk—benefit of anti-TNF dose tapering or withdrawal over maintenance should be carefully examined in both early and established RA patients.