Cost-Effectiveness of Therapeutic Drug Monitoring-Guided Adalimumab Therapy in Rheumatic Diseases: A Prospective, Pragmatic Trial

Abstract

Introduction: To assess the clinical and cost-effectiveness of therapeutic drug monitoring (TDM) based on serum adalimumab levels compared to standard of care in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis.

Methods: This was a non-inferiority, multicentric, non-randomized, pragmatic trial including adult patients diagnosed with moderate-to-severe, clinically stable rheumatic diseases treated with adalimumab. Consecutive patients were assigned 1:2 to the control (CG) or the intervention group (IG), based on the site of inclusion, and followed up for 18 months. Adalimumab serum levels were measured at each study visit and released to the IG only to modify dosing strategy. Data on disease activity, healthcare resource utilization and health-related quality of life (HRQoL) measured through the EQ-5D-5L were collected. Number of persistent and overall flares, time to first flare, days experiencing high disease activity, total direct costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER) were calculated.

Results: Of the 169 recruited patients, 150 were included in the analysis (52 and 98 patients in the CG and IG, respectively). The primary endpoint was not met as persistent flares were not significantly lower in the IG, although mean (SD) number of flares was numerically lower in the IG (0.67 [0.70] versus 0.90 [0.82], P = 0.073), respectively. Based on EQ-5D-5L utilities, HRQoL was significantly higher in the IG at 3 (P = 0.001) and 6 months (P = 0.035), which overall translated into 0.075 QALYs gained per patient for the IG at month 18. Overall, direct costs were significantly lower for the IG patients (€15,311.59 [4,870.04] versus €17,378.46 [6,556.51], P = 0.030), resulting in the intervention being dominant, leading to increased QALY at a lower overall cost CONCLUSION: Adalimumab dose tapering based on TDM for rheumatic patients led to an increased quality of life and QALY gain and entailed lower costs, being a more cost-effective alternative than clinically guided management.

Keywords: Adalimumab; Cost-effectiveness; Rheumatic diseases; Therapeutic drug monitoring.

Fig. 1

Patient recruitment and follow-up flow diagram. Patients were assigned to dose reduction strategy (interventional group, IG) or standard care (control group, CG) in a 2:1 ratio. RA rheumatoid arthritis; PsA psoriatic arthritis; AS ankylosing spondylitis; ITT intention to treat; PP per protocol

Fig. 2

Health-related quality of life (HRQoL). Change in EQ-5D-5L quality of life. a Utility index and b VAS index for 18 months' follow-up. Patients were visited every 3 months according to their current clinical status, although the number of completed visits was not homogeneous. Number of patients per visit in the control group (CG) and in the intervention group (IG) were at baseline (n = 52; n = 98), visit 1 (n = 51; n = 98), visit 2 (n = 48; n = 94), visit 3 (n = 48; n = 94), visit 4 (n = 48; n = 85), visit 5 (n = 42; n = 84) and visit 6 (n = 35; n = 74). Data are expressed as mean ± 1.96*SEM. *P < 0.05 (IG versus CG). The frequency of visits was between 12 and 16 weeks and followed the clinical practice of each site. The number of visits completed per patient was not homogeneous

Fig. 3

Cost-effectiveness analysis. a Incremental cost-effective ratio (ICER) analysis, including 5000 bootstrapping replications per group for the comparison of IG versus CG during the 18-month follow-up. QALY quality-adjusted life years. b Mean incremental net monetary benefit (NMB) for the bootstrap replications at different WTPs with 95% confidence intervals evidencing that measuring DL to inform therapeutic decisions is a cost-effective (positive) intervention. WTP willingness to pay; ll lower limit; ul upper limit