Association of baseline C-reactive protein and prior anti-tumor necrosis factor therapy with need for weekly dosing during maintenance therapy with adalimumab in patients with moderate to severe Crohn's disease.

OBJECTIVE: A post hoc analysis of data from the adalimumab Crohn's disease (CD) maintenance trial (CHARM, NCT00077779), examining the relationship between adalimumab dosing and maintenance of remission and response in subgroups stratified by previous anti-TNF use and baseline CRP.

METHODS: All patients received open-label induction (adalimumab: 80 mg, week [wk] 0; 40 mg, wk 2). At wk 4, all patients were randomized to double-blind maintenance adalimumab (40 mg weekly or every other week [eow]) or placebo for 52 weeks. In this analysis, clinical remission (CDAI <150) and clinical response (CR-100) at wk 26 and wk 56 by baseline CRP (high: ≥ 10 mg/L, or low: <10 mg/L) and prior anti-TNF use were determined for patients with CR-70 at wk 4.

RESULTS: Of 498 patients in this analysis, 260 (52.2%) were anti-TNF-naïve. For anti-TNF-naïve patients, the wk 56 remission rates in the adalimumab groups were significantly greater than placebo (P < 0.05) for both high and low CRP cohorts, with no statistically significant differences between remission rates with eow and weekly dosing within each CRP cohort (high: 52.8% eow, 53.5% weekly; low: 34.7% eow, 41.9% weekly). For anti-TNF-exposed patients, wk 56 remission rates were higher than placebo with both eow and weekly dosing within each cohort; weekly dosing in the high CRP cohort and eow dosing in the low CRP cohort achieved statistical significance (P < 0.05). In the high CRP cohort, remission rate with weekly dosing (46.9%) was statistically significantly greater compared with eow dosing (22.5%). There were no significant differences between eow (23.1%) and weekly (37.0%) dosing in the low CRP group. For all subgroups, clinical remission (wk 26) and clinical response (wk 26 and wk 56) patterns were similar to those observed for wk 56 remission.

CONCLUSIONS: These subgroup analyses suggest that in patients with moderately to severely active CD, weekly dosing may be most effective in the anti-TNF-experienced patients with elevated CRP at baseline.