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Adalimumab for treatment of Crohn disease in adults

Authors
Robert M Penner, BSc, MD, FRCPC, MSc
Richard N Fedorak, MD, FRCPC
Section Editor
Paul Rutgeerts, MD, PhD, FRCP
Deputy Editor
Shilpa Grover, MD, MPH

INTRODUCTION

Adalimumab (Humira) is a recombinant human IgG1 monoclonal antibody directed against tumor necrosis factor that has been approved for use in rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and Crohn disease. Unlike infliximab, which requires an intravenous infusion, adalimumab is administered by subcutaneous injection.

This topic review will focus on the role of adalimumab in Crohn disease, while its role in other disorders is presented separately. (See appropriate topic reviews).

EFFICACY FOR INDUCTION AND MAINTENANCE

Regulatory approval for adalimumab was based upon three pivotal studies (CLASSIC-I, CHARM, and GAIN) that focused on its role as induction therapy, maintenance therapy, and therapy in patients who had lost response to or were intolerant of infliximab, respectively. A fourth study (CLASSIC-II) provided follow-up of CLASSIC-I by assessing maintenance therapy in patients who were in remission following induction. EXTEND is an additional trial that examined adalimumab for induction and maintenance therapy. EXTEND differed from previous trials with adalimumab in that its primary objective was mucosal healing.

The CLASSIC-I trial included 299 patients with moderate to severely active Crohn disease despite concomitant therapies (including one or more of mesalamine, glucocorticoid, immunosuppressive agents, and antibiotics) who had no previous exposure to tumor necrosis factor (TNF) antagonists. They were randomly assigned to adalimumab at three different doses or placebo at zero and two weeks [1]. The primary endpoint was induction of clinical remission after four weeks. A linear dose-response curve was demonstrated, with the most effective dose being the highest studied: a loading dose of 160 mg at week 0 followed by 80 mg at week 2. Remission (Crohn disease activity index [CDAI] <150 points) at four weeks was achieved significantly more often in patients receiving the 160 mg/80 mg dose compared with placebo (36 versus 12 percent). Similarly, a response (CDAI decrease of 100 points) at four weeks was achieved significantly more often in patients who received the 160 mg/80 mg dose compared with placebo (50 versus 25 percent).

The CLASSIC-II trial included a total of 276 patients from CLASSIC-I who received open-label adalimumab (40 mg) at weeks 0 and 2 [2]. Fifty-five patients who were in remission at both weeks 0 (week 4 of the CLASSIC-I trial) and 4 were re-randomized to three treatment groups: placebo or adalimumab 40 mg every other week or 40 mg weekly for 56 weeks. Patients who were not in remission at both weeks 0 and 4 received open-label adalimumab 40 mg every other week. In those who did not respond or who had a flare, the dose could be increased to 40 mg weekly. The primary endpoint was clinical remission after 56 weeks.

Of the 55 patients randomized at week 4, remission at week 56 was seen in 79 percent of adalimumab 40 mg every other week, 83 percent of 40 mg weekly, and 44 percent of those treated with placebo. Response at week 56 was seen in 89 percent, 79 percent, and 56 percent, respectively. These data suggest that the maintenance of remission can be achieved in the majority of patients who achieved remission with induction therapy.

Of the 204 who entered the open-label arm, 46 percent were in clinical remission and 65 percent were considered responders at week 56. That the open-label arm had a lower percentage of patients in remission compared with the randomized arm implies that patients in full remission after their induction of adalimumab have a greater chance of staying in remission after one year. Approximately one-half of the patients in the open-label arm had increased the dose of adalimumab from every other week to weekly by week 56.

Patients generally respond within the first week. However, in some patients, the response to adalimumab was not fully achieved until week 12 after induction. This observation suggests a time frame that may be required for assessing the clinical response and need for maintenance therapy.

           

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Literature review current through: Nov 2016. | This topic last updated: Wed Dec 16 00:00:00 GMT+00:00 2015.
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