Biological therapy in Crohn's disease: Is it an issue of how hard you strike or how fast you strike?

✍ Scribed by Remo Panaccione

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 49 KB
• Volume: 15
• Category: Article
• ISSN: 1078-0998
• DOI: 10.1002/ibd.20627

✦ Synopsis

D 'Haens et al recently published the results of an open label, randomized, multicenter study evaluating 2 distinct treatment algorithms in 129 patients with moderately to severely active Crohn's disease (CD) (Crohn's Disease Activity Index [CDAI] 220-450) who were within 4 years of diagnosis and had never been treated with systemic steroids, immunomodulators, or biologic therapy. Patients were randomized to treatment using either the traditional step-up approach or a more aggressive early combined immunosuppressive (top-down) approach. In the conventional step-up approach, patients were treated with corticosteroids (prednisone or budesonide) as first-line therapy and azathioprine was added to the regimen for patients who required repeated courses of steroids or became steroid-dependent. Infliximab was eventually added if these therapeutic interventions failed (i.e., immunosuppression failure). In the top-down approach, patients received infliximab as a 3-dose induction regimen (infliximab 5 mg/kg; 3 infusions at weeks 0, 2, and 6) along with azathioprine (2.0 -2.5 mg/kg) followed by infliximab in an on-demand fashion if symptoms recurred or worsened. Patients who were intolerant to azathioprine were switched to methotrexate 25 mg SC weekly. Systemic steroids were only added if patients did not respond to the combination of infliximab and azathioprine.

The co-primary endpoints of the study were corticosteroid-free remission (CDAI Ͻ150) without need for surgery at week 26 and week 52. In the top-down group remission rates were significantly higher at both timepoints (week 26; 60% versus 36%, P ϭ 0.006; week 52; 62% versus 42%, P ϭ 0.03). Furthermore, after 2 years of treatment patients assigned to the top-down strategy were more likely to achieve complete endoscopic remission than those who received stepup treatment (73% versus 30%, P ϭ 0.003).

Drug exposure was different between the 2 strategies, as would be expected. At 1 year, no patients in the top-down group were on corticosteroids as compared to the step-up group, where at the end of 1 year 17% were still receiving treatment with corticosteroids at an average dose of methylprednisolone Ͼ20 mg. Ninety percent of patients in the top-down group was on immunosuppressive therapy at 1 year compared to 62% in the step-up group. At 1 year the rate of infliximab use was similar.