Background Serum adalimumab should optimally be maintained at ≥3 mg/L during treatment of patients with rheumatoid arthritis (RA). Grey scale (GS) and power Doppler (PD) ultrasound (US) are sensitive modalities for the evaluation of synovitis during biologic therapy.
Objectives The objective of this pilot study was to explore, using ultrasound and clinical assessments, treatment response in RA patients with adalimumab serum concentrations < or ≥3mg/L.
Methods Twenty RA patients on methotrexate (MTX) were examined the day they started adalimumab treatment as well as after 3 and 6 months. The patients were assessed by ultrasound of 78 joints with semi-quantitative (0-3) scoring of GS and PD. Sum scores for GS and PD for all 78 joints were calculated. All patients were assessed clinically and by ESR. Serum samples were collected, frozen at -70°C and retrospectively assayed for adalimumab and anti-adalimumab antibodies. Changes from baseline were calculated for sum GS/PD scores and clinical examinations/ESR and used as response variables. At each follow-up, patients were sub-grouped based on serum adalimumab < or ≥3mg/L, and differences between the groups were explored by use of independent samples T test. Adalimumab and anti-adalimumab were measured using in-house assays established at Oslo University Hospital.
Results After 3 months, two patients had adalimumab concentrations below 3 mg/L (0.2 and 1.6 mg/L) while the remainder had median concentrations of 7.5 (3.0 - 16.0) mg/L. At 6 months follow-up six patients had low adalimumab levels (median 0.95 (0.0–2.6)) while the remainder had a median 10.65 (5.2–20.8) mg/L. At 6 months two patients had stopped MTX treatment due to intolerance (both had high serum adalimumab). Sum GS/PD scores and assessor's (study nurse) evaluation of disease activity differed between the groups, with decreased improvement in patients with low levels of adalimumab, while significant difference was not detected by clinical examinations/ESR (table illustrates mean (SD) changes from baseline for all the variables). Five patients developed antibodies against adalimumab during the 6-months follow-up. These patients had significantly lower serum concentrations of adalimumab (mean (SD) at 3 months 3.6 (2.7) vs 8.3 (3.9) mg/L, p=0.014 and at 6 months 2.3 (4.2) vs 10.1 (5.6) mg/L, p=0.009) as well as having lower sum score GS and PD, assessor's VAS and ESR at 6 months (p<0.05).
Conclusions Ultrasound detected clear differences between patients with low vs. therapeutic adalimumab concentrations. Differences were also found by assessor's VAS. On the other hand, neither DAS28 nor ESR differed between the groups. The present study finds ultrasound to be a sensitive tool for evaluation of treatment response and indicates that assessments of serum adalimumab is useful for identifying patients with insufficient drug levels.
Disclosure of Interest None declared