Infliximab, azathioprine, or combination therapy for Crohn's disease
Jean Frédéric Colombel, William J Sandborn, Walter Reinisch, Gerassimos J Mantzaris, Asher Kornbluth, Daniel Rachmilewitz, Simon Lichtiger, Geert D'Haens, Robert H Diamond, Delma L Broussard, Kezhen L Tang, C Janneke van der Woude, Paul Rutgeerts, SONIC Study Group, N Ahluwalia, C Antonson, G Arnold, M Astroff, G Aumais, F Baert, I Bassan, S Becker, R Befrits, F Bendtsen, M Bigard, B Bokemeyer, S Bologna, B Bonaz, M Bradette, R Braun, J Cappa, J F Colombel, J Dahlerup, W Denton, J Deus, O Dewit, G D'Haens, A Dignass, A Sturm, J Dimitroff, B Dolin, I Dotan, J Dupas, A Eliakim, J Fallingborg, M Fleisher, G Fraser, J Goff, V Gonzalez, L Menchen Viso, G Gordon, S Ghosh, M Gould, R Hansen, J Hanson, W Harlan 3rd, E Hertervig, J Hinojosa, W Holderman, S Howaldt, D Hueppe, J Jahnsen, S Katz, B Kaufman, M Kestell, G Kitis, F Konikoff, A Kornbluth, I Kouroumalis, G Koval, T Kucharzik, A Luegering, D Laharie, M Lémann, S Lichtiger, E Louis, P Malfertheiner, G Mantzaris, R Matsuyama, P Miner, J Moreau, T Ochsenkuehn, F Opper, B Oubre, M Parkes, M Perkel, F Portela, M Priebe, C Probert, D Rachmilewitz, A Raedler, C Randall, E Ricart Gomez, E Garcia Planella, D Rosenberg, P Rutgeerts, W J Sandborn, S Schreiber, U Seidler, I Shafran, D Stanton, M Stern, H Tilg, G Van Assche, C Janneke van der Woude, D Weinberg, A Williams, E Williams, R Wohlman, J Wolosin, Jean Frédéric Colombel, William J Sandborn, Walter Reinisch, Gerassimos J Mantzaris, Asher Kornbluth, Daniel Rachmilewitz, Simon Lichtiger, Geert D'Haens, Robert H Diamond, Delma L Broussard, Kezhen L Tang, C Janneke van der Woude, Paul Rutgeerts, SONIC Study Group, N Ahluwalia, C Antonson, G Arnold, M Astroff, G Aumais, F Baert, I Bassan, S Becker, R Befrits, F Bendtsen, M Bigard, B Bokemeyer, S Bologna, B Bonaz, M Bradette, R Braun, J Cappa, J F Colombel, J Dahlerup, W Denton, J Deus, O Dewit, G D'Haens, A Dignass, A Sturm, J Dimitroff, B Dolin, I Dotan, J Dupas, A Eliakim, J Fallingborg, M Fleisher, G Fraser, J Goff, V Gonzalez, L Menchen Viso, G Gordon, S Ghosh, M Gould, R Hansen, J Hanson, W Harlan 3rd, E Hertervig, J Hinojosa, W Holderman, S Howaldt, D Hueppe, J Jahnsen, S Katz, B Kaufman, M Kestell, G Kitis, F Konikoff, A Kornbluth, I Kouroumalis, G Koval, T Kucharzik, A Luegering, D Laharie, M Lémann, S Lichtiger, E Louis, P Malfertheiner, G Mantzaris, R Matsuyama, P Miner, J Moreau, T Ochsenkuehn, F Opper, B Oubre, M Parkes, M Perkel, F Portela, M Priebe, C Probert, D Rachmilewitz, A Raedler, C Randall, E Ricart Gomez, E Garcia Planella, D Rosenberg, P Rutgeerts, W J Sandborn, S Schreiber, U Seidler, I Shafran, D Stanton, M Stern, H Tilg, G Van Assche, C Janneke van der Woude, D Weinberg, A Williams, E Williams, R Wohlman, J Wolosin
Abstract
Background: The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for Crohn's disease are unknown.
Methods: In this randomized, double-blind trial, we evaluated the efficacy of infliximab monotherapy, azathioprine monotherapy, and the two drugs combined in 508 adults with moderate-to-severe Crohn's disease who had not undergone previous immunosuppressive or biologic therapy. Patients were randomly assigned to receive an intravenous infusion of 5 mg of infliximab per kilogram of body weight at weeks 0, 2, and 6 and then every 8 weeks plus daily oral placebo capsules; 2.5 mg of oral azathioprine per kilogram daily plus a placebo infusion on the standard schedule; or combination therapy with the two drugs. Patients received study medication through week 30 and could continue in a blinded study extension through week 50.
Results: Of the 169 patients receiving combination therapy, 96 (56.8%) were in corticosteroid-free clinical remission at week 26 (the primary end point), as compared with 75 of 169 patients (44.4%) receiving infliximab alone (P=0.02) and 51 of 170 patients (30.0%) receiving azathioprine alone (P<0.001 for the comparison with combination therapy and P=0.006 for the comparison with infliximab). Similar numerical trends were found at week 50. At week 26, mucosal healing had occurred in 47 of 107 patients (43.9%) receiving combination therapy, as compared with 28 of 93 patients (30.1%) receiving infliximab (P=0.06) and 18 of 109 patients (16.5%) receiving azathioprine (P<0.001 for the comparison with combination therapy and P=0.02 for the comparison with infliximab). Serious infections developed in 3.9% of patients in the combination-therapy group, 4.9% of those in the infliximab group, and 5.6% of those in the azathioprine group.
Conclusions: Patients with moderate-to-severe Crohn's disease who were treated with infliximab plus azathioprine or infliximab monotherapy were more likely to have a corticosteroid-free clinical remission than those receiving azathioprine monotherapy. (ClinicalTrials.gov number, NCT00094458.)
2010 Massachusetts Medical Society
Source: PubMed