Comparison of Two Adalimumab Treatment Schedule Strategies for Moderate-to-Severe Crohn's Disease: Results From the CHARM Trial

• Published in: The American journal of gastroenterology Vol. 104; no. 5; pp. 1170 - 1179
• Main Authors: COLOMBEL, Jean-Frédéric, SANDBORN, William J, RUTGEERTS, Paul, KAMM, Michael A, YU, Andrew P, WU, Eric Q, POLLACK, Paul F, LOMAX, Kathleen G, JINGDONG CHAO, MULANI, Parvez M
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.05.2009; Wolters Kluwer Health Medical Research, Lippincott Williams & Wilkins
• Subjects: Adalimumab; Adolescent; Adult; Aged; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal, Humanized; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Canada; Crohn Disease - diagnosis; Crohn Disease - drug therapy; Dose-Response Relationship, Drug; Drug Administration Schedule; Europe; Female; Follow-Up Studies; Gastroenterology; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Immunomodulators; Injections, Subcutaneous; Male; Maximum Tolerated Dose; Medical sciences; Middle Aged; Other diseases. Semiology; Pharmacology. Drug treatments; Probability; Quality of Life; Reference Values; Risk Assessment; Severity of Illness Index; Statistics, Nonparametric; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Treatment Outcome; Tumor Necrosis Factor-alpha - antagonists & inhibitors; United States; Young Adult; Canada; United States; Europe; Cytokine; Antipsoriatic agent; Monoclonal antibody; Anti-Tumor Necrosis Factor-alpha; Inflammatory disease; Immunomodulator; Crohn disease; Treatment; Anticytokine; Gastroenterology; Digestive diseases; Intestinal disease; Antirheumatic agent; Adalimumab; Tumor necrosis factor α; Comparative study
• ISSN: 0002-9270; 1572-0241
• DOI: 10.1038/ajg.2009.59

To compare outcomes of induction dosing followed by continuous adalimumab treatment with those of induction dosing with reinitiation of adalimumab (in the event of clinical deterioration) for patients with moderate-to-severe Crohn's disease (CD) who participated in the Crohn's Trial of the Fully Human Antibody Adalimumab for Remission Maintenance (CHARM). In the CHARM trial, all patients received open-label induction therapy with adalimumab 80 mg and 40 mg at weeks 0 and 2, respectively. In total, 778 patients were randomized at week 4 to one of three groups: (1) placebo after initial induction doses (followed by reinitiation of adalimumab therapy); (2) continuous maintenance treatment with adalimumab 40 mg every other week (e.o.w.); and (3) continuous maintenance treatment with adalimumab 40 mg every week. At/after week 12, patients receiving placebo with flare or non-response could reinitiate open-label adalimumab 40 mg e.o.w., and patients receiving continuous blinded adalimumab therapy could switch to open-label 40 mg e.o.w. Patients in all groups could switch to weekly therapy with continued flare/non-response. In the previously published primary analysis, results for only those patients who had responded at week 4 (decrease in Crohn's Disease Activity Index (CDAI) of > or = 70 points, referred to as "randomized responders") and remained on blinded therapy were analyzed. In this analysis, data from all randomized patients were analyzed based on original randomized treatment using an intention-to-treat analysis, regardless of whether they subsequently switched to open-label therapy. Disease activity, clinical remission, number of flares, Inflammatory Bowel Disease Questionnaire (IBDQ) score, number of CD-related surgeries, and hospitalization incidence were compared between the continuous and induction only/reinitiation adalimumab groups. Results for all outcome measures were superior for both continuous groups compared with the induction only/reinitiation group. On the basis of median CDAI and IBDQ results, patients in both continuous treatment groups achieved statistically significantly greater improvements vs. the induction only/reinitiation group (P < 0.05). At week 56, a significantly greater percentage of patients who had received continuous adalimumab (51% for e.o.w. and 49% for weekly) were in clinical remission vs. the induction only/reinitiation group (38%, P < 0.05). Continuous adalimumab therapy was also associated with fewer flares and fewer CD-related surgeries (P < 0.05). Patients in both continuous adalimumab groups had significantly lower risks of CD-related and all-cause hospitalizations than did patients in the induction only/reinitiation group (P < 0.05). For patients with active CD, continuous treatment with adalimumab was more effective than a strategy of induction dosing followed by reinitiation of adalimumab with clinical deterioration for maintenance of clinical remission, improved quality-of life outcomes, reduced flares, and a decrease in number of surgeries and risk of hospitalization.