To analyze the clinical relevance, in clinical practice, of adalimumab (ADA) serum levels (SL) and anti-ADA antibodies (anti-ADA-Abs). 2. To evaluate if there is correlation between SL of ADA and result of DAS28. 3. To determine the minimum appropriate SL of ADA to keep the patients in remission or in low clinical activity.
Methods Serum levels of ADA and anti-ADA-Abs (ELISA kit. Promonitor®-ADA. Proteomika, Derio. Vizcaya. Spain) were analyzed in patients with rheumatoid arthritis (RA) receiving ADA >6 months. Cut-off level for serum Abs anti-ADA was >32 U/mL and for serum level of ADA <0.004 mg/L. Clinical characteristics, clinical activity index (DAS in 28 joints), using ESR, were recorded. All the patients were receiving DMARD (methotrexate, leflunomide or hydroxychloroquine).
Serum samples were collected before injection of ADA (same day), and stored frozen until analysis. Patients were considered on clinical remission if they had at the same time of extraction, DAS28≤2,6, and low clinical activity if DAS28 between 2,7-3,2.
The patients was distributed in tertiles groups from serum levels of ADA: <2,8 mg/L; 2,9-7,3 mg/L; >7,3 mg/L. ROC curvewas used to select optimus cut-off level of ADA to keep the patients on remission or low activity level of disease. Finally, correlation between DAS28 and SL of ADA was evaluated.
Results We included 63 determinations from 56 patients with RA. 75% were women; mean age: 62 years. The average time of evolution of RA was 156±122 months, and for the treatment of ADA 32,26±18,31months. ADA was the first anti-TNF received in 80% of patients. The distribution of DMARDs: methotrexate: 65% (mean dose: 15 mg), leflunomide: 21% (18 mg) and hydroxychloroquine: 14% (200 mg). In 4 (7%) patients anti-ADA Abs was detected; all in the group of SL of ADA <2,8 mg/L.
We obtained a negative relation between SL of ADA and DAS28 (r: -0.46. CI 95%: -0.66,-0.21). The cut-off of SL of ADA in ROC curves was, for DAS28≤2,6: 3,01 (AUC: 65,77%; sensitivity: 50% y specificity: 77,77%); for DAS28 2,7-3,2: 3,48 (AUC: 83,18%; sensitivity: 83,33% y specificity: 77,80%). Table show the relation of SL of ADA anti-ADA Abs and DAS28-ESR, according ADA tertiles.
The cut-off of ROC curve for serum level of ADA, to keep the patients in low activity of disease is 3,45 mg/L. 2. There is a negative correlation between the serum level of ADA and DAS28. 3. Serum level of ADA >7,3 mg/L does not increase the improvement of DAS28. In these patients, we can consider to decrease the ADA dose or its delay. 4. The prevalence of anti-ADA Abs in patients with RA treated with ADA and DMARD is 7%.
Disclosure of Interest None Declared