Adalimumab maintains remission of Crohn's disease after up to 4 years of treatment: data from CHARM and ADHERE

Abstract

Background: Therapies that maintain remission for patients with Crohn's disease are essential. Stable remission rates have been demonstrated for up to 2 years in adalimumab-treated patients with moderately to severely active Crohn's disease enrolled in the CHARM and ADHERE clinical trials.

Aim: To present the long-term efficacy and safety of adalimumab therapy through 4 years of treatment.

Methods: Remission (CDAI <150), response (CR-100) and corticosteroid-free remission over 4 years, and maintenance of these endpoints beyond 1 year were assessed in CHARM early responders randomised to adalimumab. Corticosteroid-free remission was also assessed in all adalimumab-randomised patients using corticosteroids at baseline. Fistula healing was assessed in adalimumab-randomised patients with fistula at baseline. As observed, last observation carried forward and a hybrid nonresponder imputation analysis for year 4 (hNRI) were used to report efficacy. Adverse events were reported for any patient receiving at least one dose of adalimumab.

Results: Of 329 early responders randomised to adalimumab induction therapy, at least 30% achieved remission (99/329) or CR-100 (116/329) at year 4 of treatment (hNRI). The majority of patients (54%) with remission at year 1 maintained this endpoint at year 4 (hNRI). At year 4, 16% of patients taking corticosteroids at baseline were in corticosteroid-free remission and 24% of patients with fistulae at baseline had healed fistulae. The incidence rates of adverse events remained stable over time.

Conclusions: Prolonged adalimumab therapy maintained clinical remission and response in patients with moderately to severely active Crohn's disease for up to 4 years. No increased risk of adverse events or new safety signals were identified with long-term maintenance therapy. (clinicaltrials.gov number: NCT00077779).

Figure 1

Disposition of CHARM patients entering ADHERE. The primary reason for discontinuation during ADHERE is also shown for all patients. ADA, adalimumab; PBO, placebo; eow, every other week; ew, weekly; OL, open-label.

Figure 2

Maintenance of clinical remission and response in patients responding to adalimumab induction therapy and receiving any dose of ADA: mITT (n = 329). (a) Crohn's disease activity index (CDAI) over time: Nonlinear model using four-parameter log-logistic function. Dotted line represents the threshold for clinical remission (CDAI <150). (b) Percentage of patients in remission (CDAI <150) over time. (c) Percentage of patients achieving clinical response (CR-100) over time. Green bars, hNRI analysis; orange bars, LOCF analysis; blue bars, as-observed.

Figure 3

Long-term maintenance of remission in patients randomised to adalimumab 40 mg eow: mITT (n = 172). Percentage of patients in remission (CDAI <150) over time. Green bars, all patients randomised to adalimumab every other week (all, hNRI analysis); orange bars, patients randomised to adalimumab every other week excluding patients that escalated to weekly dosing (no dose escalation, hNRI analysis); blue bars, patients randomised to adalimumab every other week excluding patients that escalated to weekly dosing (no dose escalation, as-observed analysis).

Figure 4

Long-term maintenance of clinical remission and response for patients in remission or response at week 56 of CHARM. (a) Percentage of patients who were in remission at the end of CHARM (CDAI <150) (n = 145) that maintained remission over time. (b) Percentage of patients who had a clinical response at the end of CHARM (CR-100) (n = 172) that maintained a response over time. Green bars, hNRI analysis; orange bars, LOCF analysis; blue bars, as-observed.

Figure 5

Long-term efficacy of fistula healing in patients randomised to adalimumab with fistulas at baseline (ITT, n = 70). Green bars, hNRI analysis; orange bars, LOCF analysis; blue bars, as-observed.

Figure 6

Maintenance of corticosteroid-free clinical remission in patients who were taking corticosteroids at CHARM baseline (ITT, n = 206) and in randomised responders, regardless of baseline corticosteroid use (mITT, n = 329). (a) Percentage of patients who discontinued corticosteroid use and achieved clinical remission (CDAI <150) over time (NRI analysis). (b) Percentage of patients who achieved corticosteroid-free clinical remission at the end of CHARM (n = 53 for the ITT population taking corticosteroids at baseline of CHARM and n = 147 for the randomised responder population) and maintained corticosteroid-free clinical remission over time (NRI analysis). Green bars, patients taking corticosteroids at baseline; orange bars, all randomised responders, regardless of baseline corticosteroid use.