Immunisation of biological drugs can result in reduced efficacy of treatment and an increased risk of adverse effects. The immunisation of biological drugs has been extensively studied in patients with rheumatoid arthritis, but less is known about the role of immunisation in the treatment of patients with ankylosing spondylitis (AS). In some studies, the development of anti-drug-antibodies (ADAb) has resulted in reduced efficacy, whereas other studies show that no correlation between the presence of ADAb and disease activity has been observed.1,2 Our aim was to study what proportion of the non-selected AS-patients attending Finnish rheumatological outpatient clinics had been immunised to the subcutaneous anti-tumour necrosis factor (TNF) drug they were using, while also studying the effect of concomitant medication on the risk of immunisation.
A total of 313 patients with AS were recruited. Blood samples were taken from 273 patients 1–2 days prior to the injection of the anti-TNF drug. Trough concentration of the anti-TNF drugs were measured with capture-ELISA (Sanquin Laboratories, Amsterdam, Netherlands), the levels of ADAb with radioimmunoassay (Sanquin Laboratories), and the residual serum TNF-blocking capacity by using reporter gene assay set up in house (United Medix Laboratories, Espoo, Finland). The clinical activity of AS was assessed using the Bath AS Disease Activity Index (BASDAI), the Bath AS Functional Index (BASFI), and the Maastricht AS Enthesitis Score (MASES).
ADAbs were observed in 21% of patients on adalimumab (n=99), in 0% of those on etanercept (n=83), in 3% of those on golimumab (n=79), and in 50% of those on certolizumab pegol (n=12). Factors affecting the immunisation of biological drugs could be further analysed in patients using adalimumab. Of adalimumab users, the drug concentration was in the target range (5–10 mg/L) in 33% of patients. Drug trough concentrations of adalimumab correlated significantly with the presence of ADAb (r: -0.54; p<0.0001). In adalimumab users, higher BMI was associated with the presence of ADAb (p=0.019, adjusted for sex, age, and the time of biological use). Methotrexate (MTX) reduced the risk of developing ADAb. Of the patients who used MTX, 12% were ADAb positive, whereas, of those who did not use MTX, 28% were ADAb positive (p=0.048 adjusted for sex, age, weight, and the duration of biological use). The use of sulfasalazine was not associated with a lower number of ADAb positive patients. The presence of ADAb resulted in lower drug trough levels, yet there was no significant correlation between the disease activity and the presence of ADAb. Of adalimumab users with ADAb+, the mean BASDAI was 1.2 (standard deviation [SD]: 1.4) and of those without ADAb 1.9 (SD: 1.9) (p=0.091). Furthermore, no significant correlation was observed between the presence of ADAb and serum erythrocyte sedimentation rate or C-reactive protein.
The disease activity of AS patients using subcutaneous anti-TNF drugs was low. The immunisation of adalimumab was relatively common in the non-selected AS patient population. The presence of ADAb resulted in lower drug trough levels, but no clear association was observed between the presence of ADAb and the disease activity. The routine monitoring of drug trough levels and/or ADAb may be indicated.