Patients with active Crohn’s disease refractory to or dependent on corticosteroids are usually treated with more potent anti-inflammatory therapy such immunomodulators or anti-TNF agents. It was the goal of the SONIC trial to find out which therapy would lead to superior outcomes: azathioprine monotherapy, infliximab monotherapy or the combination of both [1,2].
The results of this trial showed an overwhelming benefit in favour of combined therapy (Fig. 1).
Not only were patients on combined treatment better off in terms of clinical remission and corticosteroid tapering, but they were significantly more likely to have mucosal healing at week 26, as well. The clinical benefit was sustained until week 52 (Fig. 2), but no further endoscopic data were collected. The superiority of the combination regimen was most pronounced in patients with elevated CRP levels and presence of ulcers at colonoscopy during baseline evaluation. Adverse events were similar among the three groups, although infusion reactions occurred more frequently with infliximab monotherapy.
Combination therapy is superior
The consequences of this trial for daily IBD management are quite important. Most physicians will still prefer to administer azathioprine/6-mercaptopurine before they embark on anti-TNF therapy, but in patients’ naïve to both drugs of the SONIC combination, it is preferable to initiate them together for a duration of at least one year. It remains unknown if it useful and safe to continue the combination beyond one year.
The SONIC results are applicable to combination therapy with thiopurines such as azathioprine but not with methotrexate. The Canadian COMMIT trial compared the efficacy of infliximab versus infliximab + methotrexate to induce steroid free remission after induction therapy with corticosteroids and failed to demonstrate additional benefit of this immunomodulator .
Furthermore, the situation is quite different for patients who have failed immunomodulators  before they are started on anti-TNF. In this situation, the IMID study by Van Assche et al. did not show benefit of continued immunomodulators beyond 6 months of combined therapy .
Finally, combined induction treatment should be reserved for patients with signs of active inflammatory disease as shown by elevated CRP levels and presence of endoscopic ulcers. It remains to be studied whether the SONIC results are also applicable to other anti-TNF agents.
1 Sandborn WJ et al (2008) SONIC: A randomized, double-blind, controlled trial comparing infliximab and infliximab and azathioprine to azathioprine in patients with Crohn’s disease naïve to immunomodulators and biologic therapy. Am J Gastroenterol 103 (Suppl 1): Abstract 1117
2 Sandborn WJ et al (2009) One year data from the SONIC study: A randomized, double-blind, controlled trial comparing infliximab and infliximab and azathioprine to azathioprine in patients with Crohn’s disease naïve to immunomodulators and biologic therapy. DDW 2009: Abstract 751f
3 Feagan BG, McDonald JWD, Panaccione R, Enns R, Bernstein C, et al (2008) A randomized trial of methotrexate in combination with infliximab for the treatment of Crohn’s disease. Presented at Digestive Disease Week; May 17-22; 2008. San Diego, CA
4 Van Assche G, Magdelaine-Beuzelin C, D‘Haens G, Baert F, Noman M, Vermeire S, Ternant D, Watier H, Paintaud G, Rutgeerts P (2008) Withdrawal of immunosuppression in Crohn‘s disease treated with scheduled infliximab maintenance: a randomized trial Gastroenterology 134: 1861-1868
Geert R. D’Haens MD, PhD
IBD / G.I. Oncology
Imelda G.I. Clinical Research Centre
Imelda General Hospital