Background/Purpose:

Government mandated dose tapering and withdrawal of biologic treatments for RA after achievement of sustained disease control is currently observed in Taiwan, the Netherlands, Denmark and the Czech Republic, among other countries. A recent systematic review reported that flares of RA signs and symptoms are associated with the withdrawal of biologics.¹ This study quantifies the direct, indirect, and total costs associated flares among early RA patients (pts) withdrawing biologics after achieving low disease activity (LDA).

Methods:

Pts from the OPTIMA trial² who were re-randomized to methotrexate (MTX) monotherapy in Period II after achieving LDA on adalimumab plus MTX combination therapy at week 26 (re-randomization baseline [RBL]) were included (N = 102). Two definitions of flare were proposed: i) Change at visit week [VW] from RBL in Disease Activity Score (DAS) 28 >0.6 and DAS 28 >3.2, and, ii) Change in Health Assessment Questionnaire (HAQ) >0.22 and HAQ ≥0.5 in pts with HAQ <0.5 at RBL. Pts who met the definitions at any VW were considered as having flares. HAQ scores were assessed i) at VW of flare for pts who had  flares and ii) at the last VW for pts who had no flares.  Average annual direct medical and indirect costs were calculated based on the mapping between HAQ scores and published 2005 German costs.³ Costs were inflated to 2012 values and differences in average annual costs were assessed between pts with and without flares.  Results were converted to currencies in the Netherlands, Denmark, Taiwan, and the Czech Republic using standard currency conversions.

Results: Among pts who discontinue biologics after achieving LDA, 34% (35 / 102) experience flares according to the DAS definition, and 25% (19 / 76) experience flares according to the HAQ definition.  Both the average annual medical cost and indirect cost for pts with flares were higher compared to those for pts without flares across all four countries regardless of which flare definition is used (Table 1). The incremental cost of flares based on the DAS28 and HAQ flare definitions were € 7,163 and € 10,190 for Germany/Netherlands, DKK 53,483 and DKK 76,081 for Denmark, TWD 301,385 and TWD 428,729 for Taiwan, and 196,498 Kč and 279,525 Kč for the Czech Republic, respectively.

Conclusion:

Flares after biologic withdrawal in early RA patients who achieved LDA are found to be costly based on the HAQ-costs mapping as published.  Real world direct assessment of the consequences of biologic withdrawal is recommended to further the understanding of this practice. 

Table 1: Direct, Indirect and Total costs for RA patients with disease flares

1.       Yoshida et al. Annals of the rheumatic diseases (2013).

2.     Kavanaugh et al. Annals of the rheumatic diseases (2012)

3.     Schädlich et al. Pharmacoeconomics (2005)