Procedures

Depending upon initial PUCAI score, patients were to be initially treated with either mesalamine (mild disease), oral CS (moderate disease), or intravenous (IV) CS (severe disease) based on standardized guidelines but with some physician discretion allowed (Figure 1). The final determination of initial therapy was made by consensus of the treating physician, patient, and family. Guidelines indicated that patients starting on mesalamine should have CS added if disease activity did not improve. Those initiated on oral or IV CS were guided to start mesalamine after 2 weeks of CS if disease activity was controlled. A detailed description of treatment guidelines as well as mesalamine dosing tables, standardized CS tapering schedules, and use of adjunctive medical therapy (e.g., rectal therapy) is provided in the on-line supplemental Appendix Page 5. Additional medical therapy in the first 12 weeks was defined as the use of an immunomodulator (thiopurine, methotrexate), calcineurin inhibitor (cyclosporine, tacrolimus), or anti-TNFα agent. The following guidelines were used to help establish the need for additional medical therapy: refractory to intravenous CS within the first 14 days per physician discretion facilitating rapid step-up therapy when needed for severely ill patients, no response to oral CS within four weeks of starting therapy, PUCAI continued to be ≥34 despite a minimum of 2–4 weeks of ≥1 mg/kg/day prednisone, failure to wean prednisone below 0.5 mg/kg/day by week 6, lack of sustained response/remission with use of mesalamine as a maintenance agent, or an adverse reaction to mesalamine preventing its use as a maintenance agent. Intolerance to mesalamine (paradoxical disease worsening, pancreatitis, hepatitis, or other significant side-effects) that precluded its use as a maintenance agent constituted a treatment failure and prompted the use of additional medical therapy. The choice of additional therapy for any patient regardless of reason was at the discretion of the attending physician. If an anti-TNFα agent and immunomodulator were started concomitantly, the anti-TNFα was considered the primary additional therapy. Patients with medically uncontrollable disease had colectomy. Rectal therapy was used at the discretion of the clinician and patient. All patients on mesalamine received study-supplied Pentasa® (Shire Pharmaceuticals Inc).

PROTECT standardized treatment guidelines.