Adalimumab induction and maintenance therapy achieve clinical remission and response in Chinese patients with Crohn's disease

Abstract

Background/aims: This was a Phase 2 study (NCT02015793) to evaluate the pharmacokinetics, safety, and efficacy of adalimumab in Chinese patients with Crohn's disease (CD).

Methods: Thirty, adult Chinese patients with CD (CD Activity Index [CDAI] 220-450; high-sensitivity [hs]-C-reactive protein [CRP] ≥3 mg/L) received double-blind adalimumab 160/80 mg or 80/40 mg at weeks 0/2, followed by 40 mg at weeks 4 and 6. An open-label extension period occurred from weeks 8-26; patients received 40 mg adalimumab every other week. Serum adalimumab concentration and change from baseline in fecal calprotectin (FC) were measured during the double-blind period. Clinical remission (CDAI <150), response (decrease in CDAI ≥70 points from baseline), and change from baseline in hs-CRP were assessed through week 26. Nonresponder imputation was used for missing categorical data and last observation carried forward for missing hs-CRP/FC values. No formal hypothesis was tested. Adverse events were monitored.

Results: Mean adalimumab serum concentrations during the induction phase were 13.9-18.1 µg/mL (160/80 mg group) and 7.5-9.5 µg/mL (80/40 mg group). During the double-blind period, higher remission/response rates and greater reductions from baseline in hs-CRP and FC were observed with adalimumab 160/80 mg compared to that with 80/40 mg. Adverse event rates were similar among all treatment groups.

Conclusions: Adalimumab serum concentrations in Chinese patients with CD were comparable to those observed previously in Western and Japanese patients. Clinically meaningful remission rates and improvement in inflammatory markers were achieved with both dosing regimens; changes occurred rapidly with adalimumab 160/80 mg induction therapy. No new safety signals were reported.

Keywords: Adalimumab; Anti-tumor necrosis factor; Crohn disease.

Conflict of interest statement

Conflict of interest: Kamm MA has been a consultant to AbbVie and has received speaker fees and research support from AbbVie. Travis S conducted no industry consulting during his time as ECCO President, but since that time has acted as advisor to, lecturer for, or been in receipt of research support from AbbVie, Boerhinger, Cosmo, Ferring, Genentech, GSK, Novo Nordisk, NPS, Pfizer, Takeda, Topivert and VHSquared. Robinson AM, Mostafa NM, Wallace K, Shapiro M, Li Y, Thakkar RB, AbbVie employees, may own AbbVie stock and/or options.

Figures

Fig. 1. Study design. a, Dose escalation to 80 mg adalimumab (ADA) every other week (EOW) at/after week 12 for disease flares/non-response. OL, Open-label.

Fig. 2. Flow diagram of patient disposition. ADA, Adalimumab. Patient disposition: number of patients enrolled, randomized, and completed the study.

Fig. 3. Mean adalimumab serum concentrations over time. Mean adalimumab concentrations during the double-blind period in adalimumab-treated Chinese patients with CD. Error bars represent SD.

Fig. 4. Clinical remission, clinical response, and CDAI over time. Percentages of patients in remission (CDAI

Fig. 5. Changes in laboratory parameters over time. Median changes from baseline in high-sensitivity-CRP protein (hs-CRP) (A), fecal calprotectin (FC) (B), and mean changes from baseline in albumin (C) concentrations over time. Error bars represent SD. Data were analyzed using last observation carried forward.