Introduction
Ustekinumab is a monoclonal antibody that targets the p-40 subunit of the interleukins IL-12 and IL-23 and is used to treat moderate to severe Crohn's disease.
Aims & Methods
The present study aims to capture the experience of a tertiary center regarding the use of ustekinumab in patients with Crohn's disease in clinical practice [real-world] settings. This is a retrospective cohort study. Demographic and disease-related data on the day of ustekinumab initiation were collected. Study primary endpoint of the study was the persistence of treatment at the end of the first year without the administration of corticosteroids (cs-free). Secondary endpoints were the persistence of treatment at the end of the first, second and fourth year with and without the need for corticosteroids. The statistical program SPSS-23 was used for the analysis.
Results
In total, 99 patients have been registered until this point [women, 52.5%; mean age 42 years, SD=16; median disease duration=6 years IQR=1.5-11;A1/A2/A3, 6.1/65.7/28.3%; L1/L2/L3/L4, 58.6/7.1/34.3/12.1%; B1/B2/B3, 51.5/30.3/18.2%; perianal disease 26%]. Among study participants, 68.7% reported history of exposure to at least one biologic agent and 35.4% had undergone a CD-related surgery. At ustekinumab initiation 6.1% were receiving concomitant azathioprine, 4% methotrexate and 32.3%corticosteroids. 75.8% (75/99) continue ustekinumab with a median duration of administration of 14.5 months (range=0.5-66). Cs-free persistence in one-year was observed in 70.1% (54/77), cs-free persistence in two-years in 59.2% (29/49), and cs-free persistence in four-years in 45% (9/20). Simple persistence in one-, two- and four-years was observed in 84.4% (65/77), 61.2% (30/49) and 55% (11/20) respectively. Seven patients (9.3%) required intensification (90mg subcutaneously every 4 weeks) and one (1.3%) required reinduction (one-time weight-adjusted intravenous administration) due to loss of response. Patients that achieved cs-free persistence in one year were associated with higher persistence in two- and four-years compared with those who received corticosteroids during the first year of ustekinumab administration (P<0.001). Patients with a history of CD-related surgery achieved higher percentages of persistence (P<0.05). In univariate logistic regression, cs-free persistence in one-year was found to be associated with Harvey-Bradshaw Index [HBI] (OR=0.81, P=0.025), CRP [mg/L] (OR=0.96, P=0.059), history of CD-related surgery (OR=3.52, P=0.041), and neutrophils>5820/μL (OR=0.19, P=0.021). In multivariate logistic regression, cs-free persistence in one-year was found only to be negatively associated with HBI (OR=0.44, 95%CI: 0.24-0.81, P=0.008). No serious infection or malignancy has been observed.
Conclusion
Our analysis showed that patients with Crohn's disease achieved high rates of persistence on ustekinumab without the need of corticosteroids administration up to 4 years after the initiation of treatment. Patients with more severe diasease at drug initiation experienced lower persistence. Long-term administration of ustekinumab is not associated with any new safety concerns.
Disclosure
GB has acted as advisor/lecturer for Janssen, Pfizer, Takeda, Abbvie, MSD, Mylan, Genesis Pharma, Adacyte Therapeutics, Amgen, Ferring, Cooper; Funding (Grants/Honoraria): Pfizer, Takeda, Abbvie, Aenorasis; Research/Clinical Trials: Abbvie, Takeda. Genesis Pharma, Cooper.