LAUSR

Whether to use biologic treatment for inflammatory bowel disease as monotherapy or in combination with immunosuppressives has been a matter of debate in the last years. We aimed to evaluate if immunosuppressants influenced the retention rate of ustekinumab in Sustain, the largest study evaluating its use in clinical practice, having the longest follow-up period reported to date. Retrospective, multicentre study (>60 sites) including patients with active Crohn′s Disease (CD) [(Harvey-Bradshaw (HBI)>4)] who received ≥1 dose of ustekinumab intravenously before July 2018. Data on concomitant immunomodulatory therapy (if any) with azathioprine, mercaptopurine, methotrexate or others at the start of ustekinumab treatment and during follow-up were documented. Clinical remission was defined as HBI≤4 and response as ≥3 points decrease from baseline. Loss of response (LoR) was defined as reappearance of symptoms that led to intensifying the treatment dose, adding another medication to control CD, switching or surgery in patients with short-term remission. The retention rate in patients on ustekinumab receiving or not immunosuppressive treatment was evaluated by descriptive analysis and Kaplan-Meier survival curves. Predictive factors were assessed by Cox-regression. Data quality was assured by remote monitoring. 463 CD patients were included. Prior CD treatments to ustekinumab were collected: the majority of patients received steroids, immunosuppressants and biologics. Figure 1 shows the percentage of patients on treatment with each type of drug and whether or not they continued to receive it when they started ustekinumab, in the case of steroids and immunosuppressants. Reasons for discontinuation of previous immunosuppressive treatments for CD were as follows: failure (37.5%), sustained remission (5.8%), adverse event (47.6%), medical decision (4%), other reasons (5.1%). During ustekinumab treatment, 163 patients (35.2%) received immunosuppressants (listed in figure 2). Sixty-six (14.3%) patients had their immunosuppressant withdrawn during treatment. Retention was observed in 77.9% of patients with concomitant immunosuppressive therapy versus 76.3% of patients without. There weren′t statistically significant differences between the two populations (p=0.712). Figure 3. The patient-year discontinuation rate for patients who didn′t receive concomitant immunosuppressants was 17.5 versus 18.9 in those who received them. No effectiveness differences were seen by adding immunosuppressants to ustekinumab, reinforcing the low immunogenic profile of this drug and reducing the risk of additional side effects and toxicity.