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P412. Pharmacokinetics of adalimumab in adult patients with moderately to severely active ulcerative colitis

W. Awni1, D. Eckert2, S. Sharma1, N. Mostafa1, P. Noertersheuser2, R. Pradhan1, A. Robinson1, W. Sandborn3, S. Hanauer4, J.-F. Colombel5, R. Thakkar1, 1Abbott Laboratories, United States, 2Abbott Laboratories, Germany, 3University of California, San Diego, United States, 4University of Chicago, United States, 5Centre Hospitalier Universitaire de Lille, Hôpital Claude Huriez, Lille, France

Background

This analysis was conducted to characterize the pharmacokinetics (PK) of adalimumab in patients (pts) with moderate to severe ulcerative colitis (UC).

Methods

Trough serum adalimumab concentrations (conc) and anti-adalimumab antibody (AAA) conc (N = 360) were measured from a 52-week (wk), randomized, double-blind, placebo-controlled Phase 3 clinical trial. Pts received adalimumab 160/80 mg at wk 0/2, and 40 mg every other wk (eow) starting at wk4 through 50. Pts who demonstrated inadequate response had the option to increase their adalimumab dose to 40 mg weekly (ew). A non-linear mixed effects modeling (NONMEM®) approach was used.

Results

The mean±SD adalimumab conc (µg/mL) in UC pts were 11.7±5.50 (wk 4), 8.68±4.81 (wk 8) and 7.97±6.09 (wk 52). Adalimumab conc increased proportionally with increasing dose in pts who had a dose increase from 40 mg eow (7.58±4.72) to 40 mg ew (13.5±6.37). Wk 8 adalimumab conc (µg/mL) were similar in patients by prior anti-TNF use (yes: 8.18±4.87; no: 9.05±4.75). Wk 8 adalimumab conc were also similar by the presence of antibodies to prior anti-TNF (yes: 8.06±5.25; no: 9.63±4.70), or use of concomitant immunosuppressants (IMM, azathioprine, 6-mercaptopurine and methotrexate) (yes: 10.0±4.09; no: 8.72±5.12). Adalimumab conc were similar at Wk 52 for prior anti-TNF, presence of antibodies to prior anti-TNF and concomitant IMM. Nineteen pts (19/360, 5.3%) were AAA positive during the study and adalimumab conc were lower in those pts. Only body weight and plasma albumin were found to be statistically significant covariates; but, they explained only 4.9% and 3.7% of the total PK variability, respectively. A combination of multiple covariates of interest (body weight, albumin, age, sex, C-reactive protein and concomitant IMM) was able to explain 13% of the total variability in PK.

Conclusion

The PK of adalimumab in pts with moderate to severe UC were similar to those observed in other adult pt populations (moderate to severe rheumatoid arthritis and Crohn's disease). Body weight and plasma albumin were identified as statistically significant baseline covariates for the variability in adalimumab PK, but each explained <5% of the total variability. The PK of adalimumab were variable between pts and even a combination of identifiable baseline covariates explained <15% of the total variability in adalimumab PK and thus were unable to account for the majority in the PK variability.