Background: The natural history of ulcerative colitis (UC) is unpredictable. The current approach is gradual step-up (SU) therapy in the majority of patients. Data on the need for and factors influencing SU therapy beyond 5ASA or steroids are understudied.
The aim of the study is to describe the first year SU therapy in patients with early UC failing on 5-ASA or steroids.
Methods: In this prospective multicentre observational trial patients with UC failing on 5-ASA and/or steroids where followed for 12 months. Patient characteristics, demographics, medical therapy, biomarkers, therapy adherence and quality of life were evaluated at every out-patient visit.
Results: A total of 103 patients (54% male, median age 40 years, median disease duration 17 months) were included. Only 2% were active smokers, while 51% were ex-smokers. Of the 103 patients 34%, 24% and 42% were 5-ASA-refractory, cortico-dependent and cortico-refractory respectively. After 1 year of follow up 81% of patients had mild or inactive UC based on the Mayo score. Sixty percent of patients had been treated with immunomodulators and 30% with biological therapy. Eighteen percent used combination therapy, representing only 54% of patients on anti-TNF therapy. The median time to initiation of immunomodulators and anti-TNF was 1 day and 55 days respectively, with a quicker initiation of anti-TNF treatment in cortico-dependent (34 days; 95% CI: 0–148) and cortico-refractory (57 days; 95% CI: 2–181) patients as compared to 5-ASA-refractory patients (97 days; 95% CI: 17–262). In total, 24/43 (56%) cortico-refractory patients started anti-TNF treatment. This was a significantly higher number compared to 4/25 (16%) of the cortico-dependent group (p=0.002) and 7/35 (20%) of the 5-ASA-refractory group (p=0.002). Biomarkers (CRP and platelet count) and clinical scores were numerically higher at initiation of anti-TNF therapy compared to immunomodulators. Whereas the use of faecal calprotectin was negligible (7%) in therapeutic decision making. Two patients underwent colectomy. Based on the results of the MMAS-8 questionnaire, patients with severe disease at baseline presented a lower median MMAS-8 score throughout the study period and thus were less adherent to therapy.
Conclusions: In patients with early UC a step up approach leads to good clinical outcomes at 1 year. Immunomodulators are initiated very early in patient flaring on 5-ASA or steroids, and up to 30% will be on anti-TNF treatment within 1 year, with cortico-refractory patients having the highest risk. Surprisingly, combination therapy is not used very often in daily clinical practice. The gradual SU and the acceleration of the therapy are based on sanguine biomarkers and clinical scores, not on faecal calprotectin levels.