Does treatment schedule matter? Once daily versus divided doses of 5-ASAs

Sulfasalazine was the first 5-ASA used to treat ulcerative colitis (UC). Because of tolerability issues, it was administered in a three times a day schedule in order to try to minimize side effects. With the development of sulfa-free 5-ASA products, the controlled trials used historical clinical experience and in vitro pharmacokinetic studies to dose their therapies to perhaps be in the most favorable light possible. However, it became clear over the years that outside of the context of a clinical trial, t.i.d. or even q.i.d. dosing led to lower patient satisfaction and overall adherence. Research demonstrated that upwards of 40% of patients were not taking their maintenance 5-ASA, and many patients cited unintentional forgetfulness as the reason. It became clear that simplifying the regimen was paramount for acceptable outcomes. Early pilot data and then controlled trials demonstrated the efficacy and safety of twice daily 5-ASA for active and quiescent UC. Now several large controlled trials demonstrate the non-inferiority and increased patient adherence and satisfaction with once daily dosing. MMX mesalamine was the first 5-ASA to receive US FDA approval in a once daily regimen. Results from the PODIUM and QDIEM trials have demonstrated acceptable effectiveness rates with favorable side effect profiles. Adherence rates remain high in real-world settings when medication is given once daily and data now suggest that once daily may be more effective than more frequently. It thus appears that the majority of patients with UC, whether with active or quiescent disease, can be treated with once daily 5-ASA.