INFLAMMATORY BOWEL DISEASE

Adalimumab for maintenance treatment of Crohn’s disease: results of the CLASSIC II trial

W J Sandborn¹, S B Hanauer², P Rutgeerts³, R N Fedorak⁴, M Lukas⁵, D G MacIntosh⁶, R Panaccione⁷, D Wolf⁸, J D Kent⁹, B Bittle¹⁰, J Li¹⁰, P F Pollack¹⁰

¹ Mayo Clinic, Rochester, MN, USA
² University of Chicago, Chicago, IL, USA
³ Universitaire Ziekenhuizen Leuven, UZ Gasthuisberg, Leuven, Belgium
⁴ University of Alberta, Edmonton, Alberta, Canada
⁵ Charles University, Prague, Czech Republic
⁶ Dalhousie University, Halifax, Nova Scotia, Canada
⁷ University of Calgary, Calgary, Alberta, Canada
⁸ Atlanta Gastroenterology Associates, Atlanta, GA, USA
⁹ Abbott Laboratories, Abbott Park, Illinois, USA
¹⁰ Abbott Laboratories, Parsippany, New Jersey, USA

Correspondence to:
Dr William J Sandborn
Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA; sandborn.william{at}mayo.edu

Background: Adalimumab induced clinical remission after four weeks in patients with active Crohn’s disease in the CLASSIC I trial.

Objective: To evaluate long term efficacy and safety of adalimumab maintenance therapy in Crohn’s disease in a follow-on randomised controlled trial (CLASSIC II).

Methods: In the preceding CLASSIC I trial, 299 patients with moderate to severe Crohn’s disease naive to tumour necrosis factor antagonists received induction therapy with adalimumab 40 mg/20 mg, 80 mg/40 mg, or 160 mg/80 mg, or placebo, at weeks 0 and 2. In all, 276 patients from CLASSIC I enrolled in CLASSIC II and received open-label adalimumab 40 mg at weeks 0 (week 4 of CLASSIC I) and 2; 55 patients in remission at both weeks 0 and 4 were re-randomised to adalimumab 40 mg every other week, 40 mg weekly, or placebo for 56 weeks. Patients not in remission at both weeks 0 and 4 were enrolled in an open-label arm and received adalimumab 40 mg every other week. With non-response or flare, these patients could have their dosages increased to 40 mg weekly. Patients in the randomised arm with continued non-response or disease flare could switch to open-label adalimumab 40 mg every other week and again to 40 mg weekly. The primary end point was maintenance of remission (CDAI <150) in randomised patients through week 56.

Results: Of 55 patients randomised at week 4, 79% who received adalimumab 40 mg every other week and 83% who received 40 mg weekly were in remission at week 56, v 44% for placebo (p<0.05). In all, 204 patients entered the open-label arm. Of these, 93 (46%) were in clinical remission at week 56. Adalimumab was generally well-tolerated in all patients.

Conclusions: Adalimumab induced and maintained clinical remission for up to 56 weeks in patients with moderate to severe Crohn’s disease naive to anti-TNF treatment.

Abbreviations: ANA, antinuclear antibodies; CDAI, clinical disease activity index; CLASSIC: Clinical Assessment of Adalimumab Safety and Efficacy Studied as Induction Therapy in Crohn’s Disease trial; IBDQ, inflammatory bowel disease questionnaire; LOCF, last observation carried forward

Keywords: gastroenterology; Crohn’s disease; adalimumab; tumour necrosis factor antagonists; randomised controlled trial

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