Italy’s Ulcerative Colitis Costs Driven by Hospital Stays as Mesalazine Adherence Falls Short

The retrospective observational study, published in the journal Drugs – Real World Outcomes, drew on administrative databases covering approximately four million beneficiaries served by six Local Health Units spread across northern, central, and southern Italy. Records from January 2010 through May 2023 were searched to identify patients with ulcerative colitis and Crohn’s disease using discharge diagnosis codes and disease-specific exemption codes, and the investigators then followed new users of mesalazine, the aminosalicylate that remains a cornerstone of mild-to-moderate ulcerative colitis management.

The study also reported epidemiological estimates for ulcerative colitis and Crohn's disease. At the end of December 2023, the estimated prevalence of ulcerative colitis was 272 per 100,000 health-assisted individuals, with a 95 percent confidence interval of 267 to 278, while Crohn’s disease prevalence stood at 166 per 100,000 (95 percent CI 162 to 170). In the same year, incidence was estimated at 18.9 per 100,000 for ulcerative colitis (95 percent CI 18 to 20) and 10.8 per 100,000 for Crohn’s disease (95 percent CI 10 to 12). When projected to the national population, these rates translate to roughly 160,625 Italians living with prevalent ulcerative colitis and 98,074 with prevalent Crohn’s disease at the end of 2023, with 11,144 new ulcerative colitis cases and 6387 new Crohn’s disease cases projected for that year alone. The authors note that previous Italian estimates were often outdated or limited to specific geographic areas, which is precisely the gap this nationwide analysis was designed to fill.

To characterize treatment in routine practice, the researchers focused on patients who were naive to mesalazine, defined by at least one year of washout without the drug, and who had at least 12 months of data available before and after starting treatment. This new-user approach is intended to minimize bias from prior exposure and to allow a homogeneous assessment of early treatment dynamics. Of 13,415 patients with ulcerative colitis identified during the inclusion period, 5320, or 40 percent, were mesalazine users, and 2552, or 48 percent of those, were classified as mesalazine-naive. Among the naive users, 1999 patients, or 78 percent, received oral mesalazine, with 116 treated with a time-dependent formulation and 1883 with a pH-dependent formulation. Oral mesalazine was also preferred over topical formulations among patients with Crohn’s disease, where 88 percent of naive mesalazine users received the oral form.

The demographic and clinical profile of the 2552 mesalazine-naive patients with ulcerative colitis revealed a population older than classical textbook descriptions suggest. The mean age at diagnosis was 50.6 years, with a standard deviation of 22.6, and the mean age at the index date was 52.5 years. Most patients fell within the 65 to 74 age group, and the sex distribution was essentially balanced, with 51.8 percent male. The most common comorbidity was infection, recorded in 1845 patients, or 72 percent, followed by hypertension in 1046 patients, or 41 percent, and diabetes in 307 patients, or 12 percent. The mean Charlson Comorbidity Index score was 0.7. Before starting mesalazine, 41.5 percent of patients had been hospitalized with ulcerative colitis as the primary diagnosis. Among extraintestinal immune-mediated conditions, endocrine disorders were the most frequent, affecting 4.7 percent of patients, followed by joint diseases at 1.2 percent.

Adherence emerged as a central concern. Using the proportion of days covered during the first year of follow-up, with adherence defined as coverage of at least 80 percent of the assumed one-tablet-per-day regimen, 69.6 percent of patients on time-dependent mesalazine met the threshold, compared with 56.1 percent of those on the pH-dependent formulation. The authors are careful to stress that these figures are descriptive rather than comparative, since the study was not designed to compare the two formulations and differences may reflect underlying differences in patient characteristics, prescribing patterns, or dosing regimens. They also caution that the 80 percent cutoff is a methodological convention commonly used in administrative database studies rather than a threshold specifically validated for mesalazine in inflammatory bowel disease, and that dispensing records do not confirm actual intake, so the measure may overestimate or underestimate true exposure.

Among patients who did not meet the adherence threshold, treatment escalation was common but conservative. Switches or add-ons of other ulcerative colitis therapies occurred in 14.7 percent of nonadherent time-dependent users and 21.0 percent of nonadherent pH-dependent users. The overwhelming majority of these changes among pH-dependent users involved systemic corticosteroids, accounting for 79.9 percent of switch or add-on treatments in that group, while only small percentages moved to topical corticosteroids, other 5-aminosalicylic acid formulations, or advanced therapies. The authors interpret this pattern as suggesting that nonadherent patients may be undercontrolled and undertreated, potentially increasing the risk of relapse or disease aggravation. Separately, the mean daily dose of oral mesalazine declined as early as the second month of treatment for both formulations, falling from approximately 4 grams to around 2 grams, a pattern the authors attribute to the transition from higher induction doses to lower maintenance doses, and possibly to remission and physician-driven dose adjustments.

Combination therapy was far from rare. Over the 2019 to 2023 observation window, monotherapy with oral mesalazine was slightly more common, ranging from 52 to 56 percent of oral mesalazine-treated patients with ulcerative colitis, meaning that roughly half of the cohort received mesalazine alongside at least one other ulcerative colitis-related treatment, whether conventional or biologic. Notably, among patients who initiated biologic therapy, 78.7 percent continued taking mesalazine afterward, indicating that clinicians frequently maintain the aminosalicylate even after starting advanced therapy. The authors suggest this reflects mesalazine’s ongoing role in ulcerative colitis management, noting that given the multiple inflammatory pathways involved in the disease, monotherapy may not always provide adequate control.

The economic analysis covered 2019 to 2023 and excluded patients who died and cost outliers, defined as values exceeding the mean by more than three standard deviations. Total mean annual costs per patient remained stable at approximately 4500 euros, ranging from 3975 to 4871 euros across the years. In 2023, the average total annual cost per patient was 4516 euros, and the single largest driver was hospitalization, at 3030 euros, followed by drugs at 1139 euros and outpatient specialist services at 419 euros. When the 2023 figures were stratified, ulcerative colitis-related hospitalizations accounted for 2158 euros, or 71 percent, of hospitalization costs, while drug spending was dominated by non-ulcerative-colitis-related dispensations, which made up 815 euros, or 72 percent, of drug costs, compared with 324 euros for ulcerative colitis-related drugs. The authors observe that hospitalization costs remained nearly three times higher than drug costs in this mesalazine-treated cohort, a finding they attribute partly to the cohort’s composition, since drug-related costs are likely kept relatively controlled by mesalazine therapy itself.

The study’s authors frame these results against a broader European and international context, noting that direct healthcare costs for ulcerative colitis have been estimated at approximately 2000 euros per patient per year in Europe, with a more recent analysis reporting mean annual direct costs of about 9000 US dollars in 2021 terms. They acknowledge important limitations: only costs traceable through administrative data were included, indirect costs such as lost work productivity were not captured, and pre-diagnostic healthcare utilization may not be attributed to inflammatory bowel disease in the records. Disease severity, extent, activity, and endoscopic outcomes could not be assessed, comorbidities were identified through proxy measures that may have resulted in incomplete identification, and the observational design precludes causal inference. Nevertheless, the analysis delivers what the authors describe as updated national estimates and a clear message: despite the arrival of biologics and small molecules, hospitalization remains the dominant cost in this population, and adherence to mesalazine falls short of optimal levels for a substantial share of patients, underscoring the need for strategies to improve adherence and optimize therapeutic pathways in routine Italian care.

Subject of Research: Real-world epidemiology, mesalazine treatment patterns, adherence, and healthcare costs of ulcerative colitis and Crohn's disease in Italy

Article Title: Real-World Epidemiology of Inflammatory Bowel Disease in Italy: Treatment Patterns, Adherence, and Costs in Patients with Ulcerative Colitis Treated with Mesalazine

Article References: Degli Esposti, L., Veronesi, C., Calabria, S., Giannessi, L., Barbieri, A., Bartolini, F., Dell’Orco, S., Ferrante, F., Grego, S., Procacci, C., Bezzio, C., & Armuzzi, A. (2026). Real-World Epidemiology of Inflammatory Bowel Disease in Italy: Treatment Patterns, Adherence, and Costs in Patients with Ulcerative Colitis Treated with Mesalazine. Drugs – Real World Outcomes. https://doi.org/10.1007/s40801-026-00591-5

Image Credits: AI Generated

DOI: 10.1007/s40801-026-00591-5

Keywords: ulcerative colitis, Crohn's disease, inflammatory bowel disease, mesalazine, adherence, healthcare costs, Italy, administrative databases, prevalence, incidence, hospitalizations, real-world evidence