Objectives To evaluate the effect of drug levels and anti-drug antibodies on the clinical efficacy and withdrawal of the anti-TNFa biologics in Chinese patients with rheumatic diseases.
Methods A cross-sectional study was performed in patients with various rheumatic disorders who were newly started on anti-TNFa treatment in the preceding 24 months. Serum samples were collected for the assay of drug levels and antibody titers against the corresponding agents. Comparison of the clinical efficacy and drug retention rate was performed between patients with and without the presence of anti-drug antibodies.
Results 58 Chinese patients were recruited (64% women). The underlying diseases that require anti-TNFa treatment were rheumatoid arthritis (RA) (60%), spondyloarthritis (SpA) (21%), psoriatic arthritis (PSA) (17%) and others (2%). The mean age was 47.8±12.9 years and the mean duration of the underlying diseases was 6.7±6.4 years. The proportion of patients treated with infliximab (IFX), adalimumab (ADA) and etanercept (ETN) was 41%, 28% and 31%, respectively. Antibodies against IFX, ADA and ETN were demonstrated in 12 (50%), 5 (31%) and 0 (0%) patients, respectively (p=0.002). Patients who developed anti-drug antibodies had significantly lower levels of the corresponding drugs (IFX level: 0.004±0.01 vs 3.81±3.49 ug/ml; p=0.002; ADA level: 0.0 vs 7.6±8.3 ug/ml; p=0.008). Compared to those without anti-drug antibodies, patients with antibodies had a significantly higher cumulative drug withdrawal rate due to inefficacy (64.7% and 71.8% vs 10.3% and 10.3% at month 12 and month 24, respectively; p<0.001). In patients with RA and PSA, the proportion of non-responders (according to the EULAR RA response criteria) was significantly higher in patients with anti-drug antibodies than those without (54% vs 11%; p=0.01). In patients with SpA, the mean improvement in ankylosing spondylitis disease activity score (ASDAS) score was significant in patients without antibodies (3.89±0.82 to 2.22±0.86; p=0.01) but not in those with anti-drug antibodies (3.40±1.67 to 3.23±1.40; p=0.73).
Conclusions: Conclusion The presence of neutralizing antibodies to the anti-TNFa biologics leads to lower serum levels of the corresponding drugs, which is associated with lower clinical efficacy and higher withdrawal rate.
Disclosure of Interest None Declared
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