Efficacy and Safety of Adalimumab by Disease Duration: Analysis of Pooled Data From Crohn's Disease Studies

Abstract

Background and aims: Analyses of Crohn's Disease [CD] studies of anti-TNF agents, including adalimumab, have reported higher remission rates among patients with shorter disease duration. To further explore the relationship between disease duration and clinical efficacy, we analysed a larger patient cohort.

Methods: Data were pooled from 10 clinical trials in patients with moderately to severely active CD who received treatment with either adalimumab or placebo. Analyses of efficacy using Crohn's Disease Activity Index [CDAI] endpoints [remission, clinical response [CR]-70, CR-100, patient-reported outcome [PRO] remission] or Harvey-Bradshaw Index [HBI] endpoints [remission/response] were conducted for induction and maintenance treatment periods. Logistic regression was used for comparisons between adalimumab and placebo treatment. Cochran-Armitage trend tests were used for comparisons between disease-duration subgroups [<1 year, ≥1-<2 years, 2-≤5 years, and >5 years].

Results: During induction, the proportion of patients achieving CDAI remission was higher in adalimumab- versus placebo-treated patients [p <0.001] and was highest [adalimumab: 45.8%] in the <1 year subgroup compared with longer disease-duration subgroups [≥1-<2 years: 31.0%; 2-≤5 years: 23.1%; >5 years: 23.6%, Cochran-Armitage p = 0.026]. In the majority of maintenance treatment analyses, patients with <1 year disease duration had the highest efficacy responses, with statistically significant differences in remission rates across disease-duration subgroups.

Conclusions: This analysis demonstrates that earlier initiation of adalimumab treatment shortly after diagnosis in patients with moderately to severely active CD leads to improved long-term clinical outcomes.

Keywords: Adalimumab; Crohn’s disease; disease duration.

Figure 1.

Efficacy at Week 4 of treatment by baseline disease duration, mNRI analysis: [A] CDAI remission, [B] CR-70, [C] CR-100, and [D] PRO remission. Analysis from CLASSIC I, GAIN, and Japan CD clinical trials; ^ap-values from logistic regression analysis for comparisons between adalimumab versus placebo treatment; ^bp-values from Cochran–Armitage trend tests comparing disease-duration subgroups ***, *, statistically significant at p = 0.001 and p = 0.05 levels, respectively. ADA, adalimumab; CD, Crohn’s disease; CDAI, Crohn’s Disease Activity Index; CR, clinical response; mNRI, modified non-responder imputation; PBO, placebo; PRO, patient-reported outcome.

Figure 2.

Efficacy [CDAI] over time by baseline disease duration, mNRI analysis: [A] CDAI remission, [B] CR-70 response, [C] CR-100 response, and [D] PRO remission. Analysis from CLASSIC II, CHARM, ADHERE, EXTEND, and Japan CD clinical trials. Last time point: Week 56 in CHARM, otherwise Week 52; p-values from Cochran–Armitage trend tests comparing disease-duration subgroups **, *, statistically significant at p = 0.01 level and p = 0.05 level, respectively. CD, Crohn’s disease; CDAI, Crohn’s Disease Activity Index; CR, clinical response; mNRI, modified non-responder imputation; PRO, patient-reported outcome.

Figure 3.

Efficacy [HBI] over time by baseline disease duration, mNRI analysis: [A] HBI remission and [B] HBI response. Analysis from CARE and ACCESS clinical trials. Last time point: Week 20 in CARE, Week 24 in ACCESS; p-values from Cochran–Armitage trend tests comparing disease-duration subgroups ***, **, *, statistically significant at p = 0.001, p = 0.01 level, and p = 0.05 level, respectively. HBI, Harvey–Bradshaw Index; mNRI, modified non-responder imputation.