Real-World Evidence of the Effectiveness and Safety of Ustekinumab for the Treatment of Crohn’s Disease: Systematic Review and Meta-Analysis of Observational Studies

Abstract

(1) Background: Evidence on the outcomes of ustekinumab treatment in real-world Crohn’s disease (CD) patients is needed. Our aim was to evaluate the effectiveness and safety of ustekinumab in CD, reported by observational studies. (2) Methods: bibliographical searches were performed (PubMed, EMBASE). Selection: observational studies assessing the effectiveness and safety of ustekinumab in CD. Exclusion criteria: studies using ustekinumab as a prophylaxis for postoperative recurrence or perianal disease. Data synthesis: effectiveness by intention-to-treat (random-effects model). Data were stratified by study design, population included, administered dose, and prior biologic exposure. (3) Results: A total of 63 studies (8529 patients) were included. Response was achieved in 60% (95% CI, 54–67%) in the short term (8–14 weeks); 64% (57–71%) in the medium term (16–24 weeks); and 64% (52–74%) in the long term (48–52 weeks). Remission was achieved in 37% (28–46%) in the short term; 42% (36–49%) in the medium term; and 45% (37–53%) in the long term. The endoscopic remission rate was 33% (25–40%) in the long term. Eighteen percent of patients lost response during follow-up. Nearly one-third of the patients needed dose optimisation, and in 59% of them it was effective. Twenty-five percent of patients developed adverse events, leading to treatment withdrawal in seven percent of the cases. (4) Conclusions: Ustekinumab is an effective and safe therapy in real-world refractory CD patients. Dose optimisation is frequently required, being effective in a high percentage of cases.

Meta‐analysis: Real‐world effectiveness and safety of ustekinumab in patients with ulcerative colitis

“…Other aspects such as clinicians' greater freedom to dose‐escalate biologics or to use concomitant treatments that are prohibited in trials, such as topical treatment, may also improve outcomes in a clinical setting. Rates and results of ustekinumab dose escalation were analysed in this meta‐analysis, indicating that almost 30% of patients needed some type of dose optimisation due to suboptimal clinical response or loss of response, a proportion almost the same as the recently reported need for ustekinumab dose escalation in CD 34 . Ustekinumab dose optimisation was clearly beneficial in our study with 40% of patients recovering clinical remission, which may have contributed to the notable pooled long‐term remission rates.…”

“…Rates and results of ustekinumab dose escalation were analysed in this meta-analysis, indicating that almost 30% of patients needed some type of dose optimisation due to suboptimal clinical response or loss of response, a proportion almost the same as the recently reported need for ustekinumab dose escalation in CD. 34 Ustekinumab dose optimisation was clearly beneficial in our study with 40% of patients recovering clinical remission, which may have contributed to the notable pooled long-term remission rates. The results of a study reporting that patients who achieved endoscopic and histological outcomes at week 16 had higher ustekinumab levels than patients who did not achieve these results may explain the benefit of increasing the dose of ustekinumab to recover response.…”

10 years of biologic use patterns in patients with inflammatory bowel disease: treatment persistence, switching and dose intensification – a nationwide population-based study

“…Although data in the clinical trial of ustekinumab in CD suggested that the long-term clinical remission rate was not different between the 8-and 12-week interval dosing groups, 22 a recent meta-analysis using real-world data reported that nearly one-third of patients with CD who started ustekinumab required dose intensification. 23 Taken together, ustekinumab has benefits in terms of persistence compared to other biologics as a first-line treatment for CD, but the administration at 8-week intervals rather than 12-week intervals may be more appropriate. Some patients prefer ustekinumab because it is known to have the longest administration interval among biologics, but clinicians should keep in mind that even in second-line treatment, the risk of dose intensification with ustekinumab is higher than that with other biologics.…”

Inflammation-Driven Colorectal Cancer Associated with Colitis: From Pathogenesis to Changing Therapy

“…In a multicentre cohort of 142 CD patients, dose escalation of ustekinumab up to every 4 weeks did not increase the risk of adverse events, including malignancies. Over a follow-up period of up to 52 weeks, only one case of cervical intraepithelial neoplasia and NMSC were reported [ 95 ].…”