Background DT&W of biologics after RA patients achieve a stable disease activity control is currently practiced in several countries including Spain. However, the economic and clinical consequences of DT&W of biologics in RA patients are unclear.
Objectives To compare the real-world, 5-year clinical and cost impact of treating RA patients who have achieved remission by maintaining biologics versus DT&W from the Spanish healthcare payer perspective.
Methods A Markov model with 1-month cycle length examined the clinical and cost impact of biologic DT&W compared to maintenance, after patients achieved remission (DAS28<2.6). Based on a systematic review of published literature till Nov. 2014, 15 published trials of 3,281 patients using the biologics adalimumab (ADA), infliximab (IFX), or etanercept (ETA) were reviewed and meta-analyzed to determine the risk of flare (loss of DAS<2.6) after treatment withdrawal, tapering (dose reduction or spacing per the strategies used in included trials), or maintenance following a period of sustained remission (DAS<2.6). Risks of flare were estimated using a fixed-effect model with exponential distribution and for each treatment strategy was stratified by RA patient type (early vs established) and treatment (ADA vs. IFX vs. ETA). After flare, re-treatment was assumed and the monthly probability of re-gaining remission was derived. Spanish costs, obtained from published literature, of disease for patients with remission and flare were combined with the cost of biologics to estimate the overall cost of each strategy.
Results In early RA patients using ADA, the mean time to flare was 20.5 months (mo), 34.8 mo, and 39.8 mo for withdrawal, tapering, and maintenance strategies, respectively (Figure 1a). Mean times to flare in established RA patients were lower with 14.6 mo, 28.1 mo, and 33.6 mo, respectively (Figure 1b). In early RA patients, five-year direct healthcare costs were lowest with the maintenance strategy (€ 5,468) and highest with the withdrawal strategy (€ 7,173); this difference was small compared to the biologics costs (€ 66,899 vs € 42,957) (biologics costs in withdrawal group are due to re-initiation of biologics upon flaring). The trend remained unchanged in established RA patients with maintenance strategy resulting in cost savings compared to withdrawal strategy in direct healthcare costs (€ 6,117 vs € 7,462) while resulting in higher biologics costs (€ 66,899 vs € 49,481). Comparing the three treatments, ADA had the longest time to flare for both RA populations and all strategies, with mean times to flare between ADA, IFX, and ETA in early RA being 20.5 mo, 16.3 mo, and 12.4 mo and in established RA being 14.6 mo, 11.3 mo, and 7.04 mo, respectively (Figure 1c and d).
Conclusions Maintenance of biologics leads to RA patients spending more time in remission at lower healthcare costs but higher biologics costs, compared to DT&W. The risk of flare is more imminent in established RA than in early RA. Future research needs to further explore willingness to pay for the sustainment of remission, and identify further patient subgroups that are at minimal risk for flare after following DT&W of biologics.
Acknowledgements The design, study conduct, and financial support for the study/trial were provided by AbbVie.
Disclosure of Interest D. Aletaha Grant/research support from: BMS, Merck, Consultant for: Abbvie, Eli Lilly, Grünenthal, Janssen, Merck, Novo Nordisk, Sanofi/Regeneron, Speakers bureau: Abbvie, Grünenthal, Janssen, Merck, Medac, Mitsubishi Tanabe, Pfizer, AstraZeneca, S. Snedecor Employee of: Pharmerit International, V. Ektare Employee of: Pharmerit International, M. Xue Employee of: Pharmerit International, Y. Bao Shareholder of: Abbvie, Employee of: Abbvie, V. Garg Shareholder of: Abbvie, Employee of: Abbvie