In both groups, treatment was escalated in a stepwise manner, from no treatment, to adalimumab induction followed by adalimumab every other week, adalimumab every week, and lastly to both weekly adalimumab and daily azathioprine. This escalation was based on meeting treatment failure criteria, which differed between groups:
• Tight control group before and after random assignment: faecal calprotectin ≥250 μg/g, C-reactive protein ≥5mg/L, CDAI ≥150, or prednisone use in the previous week.
• Clinical management group before random assignment: CDAI decrease of <70 points compared with baseline or CDAI >200; and after random assignment: CDAI decrease of <100 points compared with baseline or CDAI ≥200, or prednisone use in the previous week.
De-escalation was possible for patients receiving weekly adalimumab and azathioprine or weekly adalimumab alone if failure criteria were not met.
The authors note that “CALM is the first study to show that timely escalation with an anti-tumour necrosis factor therapy on the basis of clinical symptoms combined with biomarkers in patients with early Crohn's disease results in better clinical and endoscopic outcomes than symptom-driven decisions alone.” They call for future studies to assess the effects of such a strategy on long-term outcomes such as bowel damage, surgeries, hospital admissions, and disability.
According to a commentary, as in treatment of rheumatoid arthritis, outcomes were improved by enrolling patients with earlier disease when, indirectly, compared with patients in phase 3 trials of tumour necrosis inhibitors. It notes that the concept of using more aggressive steroid-sparing therapies was first advanced by the 2008 “Top-Down, step up” study comparing early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease. Furthermore, in the absence of imaging quantification of transmural disease, the STRIDE consensus recommended a treat-to-target approach for Crohn's disease based on resolution of symptoms and endoscopically assessed ulcerations. The commentator suggests that “despite not yet achieving disease modification, evidence continues to accrue that treating more than just symptoms and targeting biological disease activity with effective steroid-sparing agents can improve long-term clinical outcomes in Crohn's disease.”