The Current Ulcerative Colitis (UC) Treatment Algorithm: From 5-ASA to Biological Therapies

Background: Ulcerative colitis (UC) is a chronic, relapsing inflammatory condition affecting the colonic mucosa, typically progressing proximally from the rectum. Incidence rates are rising globally. The etiology is multifactorial, involving genetic susceptibility and environmental triggers such as smoking status and diet. Aim: The aim of this article is to provide a comprehensive review of the current therapeutic landscape for ulcerative colitis, evaluating the efficacy and safety of established and novel pharmacological agents based on a systematic review of clinical trials and meta-analyses. Materials and Methods: The review included scientific papers sourced from the PubMed and Google Scholar databases. Results: Treatment strategies vary by disease severity. 5-aminosalicylates (5-ASA) remain the first-line therapy for inducing and maintaining remission in mild-to-moderate UC. For moderate-to-severe disease, corticosteroids are effective for induction but limited by systemic toxicity, leading to the development of second-generation formulations like Budesonide MMX. In steroid-refractory or dependent cases, biological therapies—including anti-TNF agents (infliximab, adalimumab), anti-integrins (vedolizumab), and interleukin inhibitors (ustekinumab) demonstrate significant efficacy. Recently, oral small molecules such as JAK inhibitors (tofacitinib, upadacitinib) and S1P receptor modulators (ozanimod) have emerged as potent, non-immunogenic alternatives. Conclusions: The management of UC has evolved from symptom control to achieving deep endoscopic remission and improving health-related quality of life. While conventional therapies remain foundational, the expansion of biologics and small molecules offers critical options for refractory patients, helping to reduce colectomy rates. Optimal treatment requires balancing therapeutic efficacy with long-term safety profiles.