Exposure–response analyses demonstrate no evidence of interleukin 17A contribution to efficacy of ABT-122 in rheumatoid or psoriatic arthritis

ABT-122 is a dual-variable-domain immunoglobulin that neutralizes both TNF-α and IL-17A. The objective of this work was to characterize exposure–response relationships for ABT-122 relative to adalimumab (TNF-α inhibitor) using ABT-122 phase 2 trials in patients with RA or PsA. Patients received subcutaneous doses of ABT-122 ranging from 60 mg every other week (EOW) to 240 mg every week, adalimumab 40 mg EOW, or placebo (PsA patients only) for 12 weeks. Relationships between ABT-122 or adalimumab serum concentrations and time course of ACR20, ACR50 and ACR70 and PASI50, PASI75 and PASI90 responses were characterized using a non-linear mixed-effects Markov modelling approach. A total of 221 RA patients and 240 PsA patients were included in the analyses. At comparable molar exposures, there was no differentiation of efficacy between ABT-122 and adalimumab and there were no consistent differences between ABT-122 and adalimumab in the potency estimates for different efficacy endpoints based on the Markov models. Plateau of ABT-122 efficacy was achieved at exposures associated with the 120 mg EOW dose in patients with RA, which were comparable to molar exposures of adalimumab 40 mg EOW, and at the lowest dose of 120 mg every week in patients with PsA. The exposure–response relationships for ABT-122 were not distinguishably different from those of adalimumab in patients with RA or PsA. Overall, there was no clear evidence that inhibition of the IL-17 pathway provided incremental benefit in the presence of TNF-α inhibition. ClinicalTrials.gov, NCT02433340, NCT02349451.