Background/Purpose: To evaluate the economic impact of
adalimumab (ADL) and etanercept (ETN) dose reduction (by decreasing treatment
frequency) and drug monitoring in patients with rheumatoid arthritis (RA) in
clinical remission.

Methods: ADL, ETN and anti-drug antibody levels were
measured using Promonitor-ADL, Promonitor-ETN, Promonitor-Anti-ADL and
Promonitor-Anti-ETN ELISA kits (Progenika, Grifols, Spain), respectively,
during 2013-2014. Cut-points for ADL and ETN levels were 0.024 and 0.035 mg/L,
respectively, and for Anti-ADL and Anti-ETN antibodies 3.5 and 132 AU/mL,
respectively. Sera were drawn immediately before each injection. Clinical
remission was defined as sustained DAS28-ESR≤2.6 during 6 consecutive
months. The following was collected: RA progress, time on biologic treatment,
reason for drug withdrawal or for resuming the conventional frequency,
ultrasound activity index (Doppler) in 12 joints, and basal (ADL every 14 days;
ETN every 7 days) and decreased (ADL every 18-21-28 days; ETN every 10-14 days)
frequencies. Annual doses avoided were calculated for the modified frequency of
ADL (every 18 days: 5.8 doses; every 21 days: 8.7 doses and every 28 days: 13
doses) and ETN (every 10 days: 15.5 doses and every 14 days: 26 doses). Savings
during the two years, and the theoretical number of patients that could have
been treated with costs saved were calculated (ADL and ETN dose prices were
500€ and 250€, respectively).

Results: Drug and anti-drug antibody levels were measured
in 45 RA patients accounting for a total of 94 tests. 87% of patients were
women, average age of 60.5±18 years. Average disease duration was 15±9.8 years
and average ADL and ETN treatment durations were 5.2±1.3 and 5.1±1.8 years,
respectively. Average time of decreased treatment frequency for both drugs was
1.2±0.7 years. ADL and ETN was the first line biological drug in 73% and 37% of
patients, respectively. Synthetic DMARDS were given in 100% and 78% of patients
on ADL and ETN, respectively. 87% of patients with a modified dosing frequency
maintained clinical remission. Two ADL patients (7%, those treated every 18
days) resumed the conventional frequency and 4 ETN patients (22%, 3/75% treated
every 10 days and 1/25% treated every 14 days: average of 6 months on modified
frequency). Anti-drug antibodies were not detected in any patient after 1 year
follow up. Table 1 summarizes clinical, drug monitoring and impact of savings
data. During 2013 and 2014 22 RA patients started biologic therapy. Cost savings
consequence of optimization allowed treatment of 22 new patients during 1 year.

Conclusion: Decreasing ADL and ETN dosing frequency
with sustained clinical activity is possible in RA patients in remission by
monitoring disease activity and serum drug levels. Dose optimization enables
significant savings. Antibodies are not detected in patients with a decreased
treatment frequency. It is likely that patients with a long term remission
require less drug level.