Centocor, Inc (HORSHAM, Pennsylvania), a member of the Johnson & Johnson family of companies, announced data from a phase IIIb study of patients with Crohn’s Disease (CD) naïve to immunomodulators and biologic therapy (SONIC) showing that a greater proportion of patients with moderate-to-severe CD receiving Remicade^® (infliximab), either in combination with azathioprine or as monotherapy, experienced steroid-free remission and mucosal healing, a study endpoint, compared with patients receiving azathioprine alone. Azathioprine is not approved in the US for the treatment of CD, however, it is approved in some countries outside the US. Nonetheless, the drug is widely used by gastroenterologists and other physicians in the US to treat CD patients.

At Week 26, a total of 57% of patients receiving Remicade combination therapy and 44% of patients receiving Remicade monotherapy achieved steroid-free remission, the primary endpoint of the study, compared with 31% of patients receiving azathioprine alone (P <.001 Remicade + azathioprine vs azathioprine monotherapy; P = .009 Remicade monotherapy vs azathioprine monotherapy; P = .022 Remicade + azathioprine vs Remicade monotherapy).

SONIC is the first clinical trial of its kind to compare the TNFα therapy with an immunomodulator in patients with moderate-to-severe CD who previously failed 5-aminosalicylate and/or steroids. The trial included >500 subjects from across the US, Europe, and Israel. Results revealed that 44% of patients receiving Remicade combination therapy and 30% receiving Remicade monotherapy achieved mucosal healing compared with 17% of patients receiving azathioprine alone (P <.001 Remicade + azathioprine vs azathioprine monotherapy; P = .023 Remicade monotherapy vs azathioprine monotherapy; P = .055 Remicade + azathioprine vs Remicade monotherapy).
Study data also showed that the safety profile of the TNFα therapy in combination or as monotherapy was similar to azathioprine monotherapy. At week 30, fully 24% of patients receiving azathioprine monotherapy experienced one or more serious adverse events compared with 16% and 14% of patients receiving Remicade monotherapy and Remicade plus azathioprine, respectively. The serious adverse events were reported in two patients receiving azathioprine monotherapy who developed colon cancer, in one receiving azathioprine monotherapy who died following a colectomy, and in one receiving Remicade combination therapy who was diagnosed with tuberculosis. Serious infections were reported were reported in eight patients in the azathioprine monotherapy group, in four receiving Remicade monotherapy, and in six receiving Remicade combination.

SONIC is a multicenter, randomized, double-blind, controlled trial that included 508 patients with CD who were naïve to both biologics and immunomodulators (azathioprine, 6-mercaptopurine, and methotrexate). Patients were randomized to three groups: 170 patients took azathioprine 2.5 mg/kg/day plus placebo infusions; 169 patients took Remicade 5 mg/kg infusions at weeks 0, 2, 6, and every 8 weeks thereafter plus placebo capsules; and 169 patients took Remicade 5 mg/kg plus azathioprine 2.5 mg/kg through 30 weeks. Fully 52% of patients were male, had a median age of 34, median weight of 70 kg, median disease duration of 2.3 years, and median baseline Crohn’s Disease Activity Index score of 275. What’s more, 49% of patients had extra-intestinal manifestations, 18% had a history of fistulas, 21% had bowel resections, 27% had been hospitalized at least once in the year prior to enrollment because of their CD, and 41% of patients were taking steroids at baseline.