Among the total population of 3.8 million INHS beneficiaries in the catchment area of the eight Italian LHUs, 9255 adults with a diagnosis of UC and 4747 adults with CD met the inclusion criteria of the study.

The analysis showed that the prevalence of UC, calculated for 31 December 2020, was 269.4 per 100,000 beneficiaries (302.1 for men and 238.4 for women) and for CD it was 141.3 per 100,000 beneficiaries (151.9 and 131.2, respectively, for men and women).

The estimated average incidence of UC, based on the overall inclusion criteria, for the period 2018 to 2020 was 20.2 per 100,000 beneficiaries and ranged between 11.1 and 25.0 per 100,000 beneficiaries.

The estimated average incidence of CD, based on the overall inclusion criteria, for the period 2018 to 2020 was 11.5 per 100,000 beneficiaries and ranged between 5.7 and 14.9 per 100,000 beneficiaries.

Considering baseline demographics characteristics of patients with UC, the mean (SD) age at inclusion (index date) was 54.0 (18.4) years, 55.1% were male, and the mean (SD) CCI was 0.6 (1.1) with a median (interquartile range [IQR]) value of 0.0 (0.0–1.0). Patients with CD were numerically younger (48.6 years; SD 18.1) and more evenly split between genders (52.2% male) than those with UC, although the CCI was similar between these IBD cohorts (Table 1). During the characterisation period, the most common comorbidities observed for patients with UC and CD were hypertension (36.6% and 29.0%, respectively), chronic obstructive pulmonary disease (19.6% and 18.6%, respectively) and dyslipidaemia (17.5% and 12.1%, respectively) (Table 1).

Prior to enrolment (i.e. during the characterisation period), more than three-quarters of patients with UC (78.7%) and CD (75.9%) were prescribed at least one IBD-related drug (Table 1). The most frequently prescribed drug category was conventional treatments: mesalazine and topical corticosteroids prescribed to patients with UC (67.4%) and CD (61.1%) and immunomodulators and systemic corticosteroids prescribed to 43.2% of patients with UC and 47.7% of patients with CD. At baseline, biologic treatments were prescribed to 2.1% and 5.1% of patients with UC and patients with CD respectively. During this period, 17.9% of patients with UC and 25.0% of those with CD had hospitalisation(s) related to the gastrointestinal tract/digestive system (Table 1).

During a mean follow-up (observation) period of 5.1 years (SD 2.6), the proportion of patients with UC who were prescribed drug treatment with at least one therapeutic agent increased to 89.3%, including 10.4% who were prescribed at least one biologic treatment. Mesalazine and topical corticosteroids were prescribed most frequently (80.7%) followed by immunomodulators and systemic corticosteroids (59.3%) (Fig. 1).

Treatment during follow-up period. IBD inflammatory bowel disease

Similarly, over a mean follow-up period of 5.3 years (SD 2.6), 88.9% of patients with CD were prescribed one or more IBD-related drug treatments, and the proportion of patients prescribed at least one biologic treatment reached 19.7%. Mesalazine and topical corticosteroids were prescribed most frequently (76.3%) followed by immunomodulators and systemic corticosteroids (63.3%) (Fig. 1).

Details regarding persistence, discontinuation, add-on and switch among patients with IBD receiving first (index) treatment with each of the three previously described drug categories are provided in Table 2. More than half of patients with UC and almost half of those with CD were persistent with index treatment comprising mesalazine and topical corticosteroids and with biologic index treatment during the follow-up period. Fewer than one-quarter of patients with IBD were persistent with immunomodulators as index treatment.

Among the 967 patients (10.4%) with UC who were prescribed a biologic treatment during the follow-up period, adalimumab (38.2%) and infliximab (31.6%) were most prescribed, followed by vedolizumab (14.1%), golimumab (12.8%) and ustekinumab (3.3%). These agents were available in Italy throughout the study follow-up period, aside from vedolizumab, which was first approved for medical use in May 2014 in the European Union. Tofacitinib was not included in this analysis as it was only reimbursed in Italy from December 2020 and at the time of enrolment fewer than 10 patients were identified receiving tofacitinib treatment.

For the 937 biologic-treated patients (19.7%) with CD, the most prescribed biologic during follow-up was adalimumab (62.3%), followed by infliximab (26.7%), vedolizumab (7.0%) and ustekinumab (3.9%).

Evaluation of treatment patterns for each biologic treatment showed that 16.2–25.2% of patients with UC who were prescribed a biologic were switched to another biologic treatment (Table 3). Among biologic treatments, the mean duration to switch (period between the first (index) biologic prescription and the switch to a different biologic treatment) ranged from 15.0 to 26.6 months. These results exclude ustekinumab, as only 32 patients received this biologic as an index drug. Regarding predictors of switching to another biologic, by controlling baseline variables assessed in the current analysis, index treatment with infliximab versus adalimumab was the only significant baseline variable associated with a significantly increased risk to switch (OR 1.82; 95% CI 1.01–3.30; P < 0.05) (Fig. S1). Ustekinumab was not included in these results as fewer than four patients were observed switching. Persistence to biologic index medication ranged from 60.8% to 68.5%, and dose escalation was reported in 6.3–38.5% of patients with UC (including ustekinumab). No baseline variables were identified as predictors of biologic treatment persistence (Fig. S2). Dose escalation was most likely with adalimumab (38.5% of patients), infliximab (30.1%) and vedolizumab (26.5%), and least likely with golimumab (14.5%) and ustekinumab (6.3%) (Table 3).

Switch from biologic index medication to another biologic during the follow-up period occurred in 13.6–23.6% of patients with CD. Among baseline variables, the CCI and presence of hypertension were significant predictors of switching to another biologic (OR 1.29, 95% CI 1.01–1.66 and OR 1.63, 95% CI 1.02–2.60; P < 0.05) while the presence of dyslipidaemia significantly decreased the risk to switch (OR 0.39; 95% CI 0.16–0.93; P < 0.05) (excluding ustekinumab because of very low patient numbers) (Table 3 and Fig. S1). Persistence to biologic index medication ranged from 65.2% to 78.1%, dyslipidaemia and psoriatic arthritis were significant predictors of treatment persistence (OR 2.41, 95% CI 1.02–5.73 and OR 0.25, 95% CI 0.08–0.80; P < 0.05) (Fig. S2). Dose escalation occurred in 18.9–46.6% of patients with CD (including ustekinumab). Dose escalation was most likely with adalimumab (46.6% of patients), followed by infliximab (26.4%) and vedolizumab (25.8%) and was least likely with ustekinumab (18.9%) (Table 3).

Healthcare resource consumption generally decreased during the follow-up period in both IBD cohorts, even though patients who died and outlier values were excluded. Patient numbers were further reduced after the first year because not all patients were followed up beyond the first year (Table 4), which may have affected results. Overall, during the entire follow-up period and for all 9157 patients with UC, the mean (SD) annual number of prescriptions/drugs was 15.5 (16.8), mean (SD) annual number of hospitalisations was 1.3 (15.3), and mean (SD) annual number of outpatient specialist services was 5.4 (8.8). Results were generally similar for patients with CD (Table 4).

The mean/median annual total direct cost per patient with UC was €7678/€1627 and that with €6925/€1991 was CD. The median costs for drugs and hospitalisations accounted for 34–44% and 22–28% of annual total costs per patient, respectively (Fig. 2).

Mean annual direct healthcare costs per patient during follow-up (outliers excluded). Data are median (interquartile range)