We read with interest the study by Reena Khanna and colleagues describing early combined immunosuppression (ECI) for the management of Crohn's disease (REACT trial). The authors aimed to compare the effectiveness of ECI treatment (an anti-TNF drug with antimetabolite treatment) with a conventional step-up approach in a real-life setting

Herfarth, H.H.

Kappelman, M.D.

Long, M.D.

Carolina Digital Repository

Immunosuppression for management of Crohn’s disease We read with interest the study by Reena Khanna and colleagues1 d e s c r i b i n g  e a r l y  c o m b i n e d immunosuppression (ECI) for the management of Crohn’s disease (REACT trial). The authors aimed to compare the eff ectiveness of ECI treatment (an anti-TNF drug with antimetabolite treatment) with a conventional step-up approach in a real-life setting. The ECI was based on the results of the so-called top-down versus step-up trial2 and the SONIC trial.3 However, there are important differences in the patient population of the REACT trial compared with these two earlier studies. Specifi cally, the earlier studies included only patients who were immunomodulator naive and anti-TNF naive, whereas in the REACT trial 30% of patients received an immunomodulator, 20% received an anti-TNF drug, and 12% of patients received a combination treatment at the time of enrolment.Additionally,  in the RE ACT study, the mean disease duration before study enrolment was more than 12 years. Because the study population in the REACT trial was not a newly diagnosed population and more than 60% of patients were already receiving some form of immunosuppression and nearly 50% had undergone surgery at the time of enrolment, we question the appropriateness of assessing “early” combined immunosuppression. Perhaps the effi  cacy of ECI would have been more pronounced in a newly diagnosed patient population naive to immunomodulators and anti-TNF drugs. Therefore, we wonder if additional analyses restricted to this population would provide additional insights. The results of these analyses would also better reflect what one would defi ne as combined immunosuppression early in the course of Crohn’s disease. MDK reports grants from AbbVie, Janssen, and J&J; and MDL reports grants from AbbVie, outside the submitted work. HHH is a consultant for Janssen.*Hans H Herfarth, Millie D Long, Michael D Kappelman hherf@med.unc.edu Department of Medicine and Department of Pediatrics, University of North Carolina, Chapel Hill, NC 27599–7080, USA1 Khanna R, Bressler B, Levesque BG, et al. Early combined immunosuppression for the management of Crohn’s disease (REACT): a cluster randomised controlled trial. Lancet 2015; 386: 1825–34.2 D’Haens G, Baert F, van Assche G, et al. Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn’s disease: an open randomised trial. Lancet 2008; 371: 660–67.3 Colombel JF, Sandborn WJ, Reinisch W, et al. Infl iximab, azathioprine, or combination therapy for Crohn’s disease. N Engl J Med 2010; 362: 1383–95.

Immunosuppression for management of Crohn's disease

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Immunosuppression for management of Crohn's disease

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