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

Wu KC, Ran ZH, Gao X, Chen M, Zhong J, Sheng JQ, Kamm MA, Travis S, Wallace K, Mostafa NM, Shapiro M, Li Y, Thakkar RB, Robinson AM - Intest Res (2016)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Xijing Hospital of the Fourth Military Medical University, Xi'an, China.

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.

No MeSH data available.


Related in: MedlinePlus

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.
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Figure 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.

Mentions: The study included an 8-week blinded phase followed by an optional 18-week open-label extension phase (Fig. 1) and a 70-day follow-up period. In the blinded phase, eligible patients were randomized 1:1 to either the standard induction or low induction adalimumab dosing regimen, with randomization stratified by CDAI (≤300 or >300). Patients randomized to the standard induction dose were treated with adalimumab 160 mg at week 0, 80 mg at week 2, and 40 mg at weeks 4 and 6, and patients randomized to the lower induction dose were treated with blinded adalimumab 80 mg at week 0, and 40 mg at weeks 2, 4, and 6. At week 8, all patients could enroll in the optional 18-week open-label extension phase to continue receiving adalimumab 40 mg every other week (EOW) up to week 24. At or after week 12, patients who experienced a disease flare (CDAI increase of ≥70 points compared to week 4 and absolute CDAI >220) or nonresponse (not achieving CR-70 on 2 consecutive visits, at least 1 week apart) could escalate their dose to adalimumab 80 mg EOW. Patients who continued to experience flares or those nonresponsive after dose escalation were to be withdrawn from the study.


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

Wu KC, Ran ZH, Gao X, Chen M, Zhong J, Sheng JQ, Kamm MA, Travis S, Wallace K, Mostafa NM, Shapiro M, Li Y, Thakkar RB, Robinson AM - Intest Res (2016)

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4863049&req=5

Figure 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.
Mentions: The study included an 8-week blinded phase followed by an optional 18-week open-label extension phase (Fig. 1) and a 70-day follow-up period. In the blinded phase, eligible patients were randomized 1:1 to either the standard induction or low induction adalimumab dosing regimen, with randomization stratified by CDAI (≤300 or >300). Patients randomized to the standard induction dose were treated with adalimumab 160 mg at week 0, 80 mg at week 2, and 40 mg at weeks 4 and 6, and patients randomized to the lower induction dose were treated with blinded adalimumab 80 mg at week 0, and 40 mg at weeks 2, 4, and 6. At week 8, all patients could enroll in the optional 18-week open-label extension phase to continue receiving adalimumab 40 mg every other week (EOW) up to week 24. At or after week 12, patients who experienced a disease flare (CDAI increase of ≥70 points compared to week 4 and absolute CDAI >220) or nonresponse (not achieving CR-70 on 2 consecutive visits, at least 1 week apart) could escalate their dose to adalimumab 80 mg EOW. Patients who continued to experience flares or those nonresponsive after dose escalation were to be withdrawn from the study.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Xijing Hospital of the Fourth Military Medical University, Xi'an, China.

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.

No MeSH data available.


Related in: MedlinePlus