Background/Purpose: Up to 40% of patients with inflammatory arthritis on TNF-α inhibitor (TNFi) treatment fail to respond either due to primary inefficacy or loss of response. Based on our previous work (1-2) and others (3), one explanation is immunogenicity leading to the development of anti-drug antibodies (ADAb) and subsequent low drug levels, which has been described in RA. Few data exist on whether such pharmacological tests correlate with treatment response in PsA. Furthermore, the value of measuring such biomarkers may be different between monoclonal antibodies and TNF receptor proteins. Our aim was to (i) evaluate whether the presence of ADAbs/drug levels predict treatment response in patients with PsA treated with TNFi drugs (ii) identify factors that may be associated with drug levels.

Methods: 75 patients were available from the Outcomes of Treatment in PsA Study Syndicate (OUTPASS) (n=49 adalimumab; n=26 etanercept), a national UK prospective observational cohort. Serum samples were collected at 3, 6 and 12 months following initiation of TNFi therapy. ADAbs were measured using radioimmunoassay (RIA) and random (non-trough) drug levels using ELISA assays at 3, 6 and 12 months. Disease activity (DAS28) scores were measured at each visit. Patient self-reported adherence to TNFi was measured at each time-point. Generalised estimating equation (GEE) was used to test the association between ADAbs and drug levels, both biomarkers and treatment response [as assessed by change in DAS28 score between pre-treatment and 12 months post-treatment (ΔDAS28)] and the association between longitudinal/baseline factors with drug levels.

Results: 264 serial samples were suitable for pharmacological testing (n= 174 adalimumab; n=90 etanercept). Mean age was 51±12 years; 61% were female; median BMI 28.9 (IQR 26.0-34.9). 20% (n=10/49) of adalimumab-treated patients were positive for ADAbs, but none were detected in etanercept-treated patients. There was no significant association between etanercept drug levels and ΔDAS over 12 months [β= -0.039 (95% CI -0.31, 0.23), p=0.77]. Using GEE, adalimumab drug levels were significantly associated with ΔDAS28 over 12 months [β= 0.055 (95% CI: 0.011, 0.099) p=0.014], but was not independently associated with ADAb level [β=-0.0015 (95% CI: -0.0031, 0.000047), p=0.057]. Adalimumab concentrations between 4.5-8.5 mg/L were associated with an optimal treatment response at 6 months using concentration-effect curves. Factors that remained significantly associated with adalimumab drug levels were ADAb level [β=-0.0073 (95% CI: -0.0014, 0.18), p<0.0001] and BMI [β=-0.15 (-0.29, -0.00450, p=0.043] in the final GEE model (adjusting for age, gender, adherence, BMI).

Conclusion: TNFi drug-level testing on samples taken at random time-points in the treatment cycle in adalimumab-initiated PsA patients may be clinically useful in determining treatment response over 12 months; interestingly, both the presence of ADAbs and BMI were inversely associated with drug levels. Identification of a drug level threshold for optimal response may help tailor adalimumab therapy for PsA patients in the future. (1) Jani M et al. Arthritis Rheumatol. 2015 May;67(8):2011-9. doi: 10.1002/art.39169. (2) Jani M et al. Ann Rheum Dis. Published Online First: [31.5.16] doi:10.1136/ annrheumdis-2015-208849 (3) Bartelds GM et al. JAMA. 2011;305(14):1460-1468

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/pharmacological-monitoring-of-adalimumab-and-etanercept-treated-psoriatic-arthritis-patients-in-predicting-future-treatment-response/