Real‐world long‐term effectiveness of ustekinumab in Crohn's disease: results from the ENEIDA registry

Abstract

Summary Background Data on the long‐term administration of ustekinumab in recommended doses are limited. Aim To assess the real‐world, long‐term effectiveness of ustekinumab in refractory Crohn's disease (CD). Methods Multi‐centre study of CD patients starting ustekinumab at the recommended dose, followed for 1 year. Values for the Harvey‐Bradshaw Index (HBI), endoscopic activity, C‐reactive protein (CRP), and faecal calprotectin (FC) were recorded at baseline and at weeks 26 and 52. Demographic and clinical data, previous treatments, adverse events (AEs) and hospitalisations were documented. Potential predictors of remission were examined. Results A total of 407 patients were analysed. The initial maintenance dose of 90 mg SC was administered every 12, 8 and 4 weeks in 56 (14%), 347 (85%) and 4 (1%) patients, respectively. After 52 weeks, treatment was discontinued in 112 patients (27.5%). At baseline, 295 (72%) had an HBI >4 points. Of these, 169 (57%) and 190 (64%) achieved clinical remission at weeks 26 and 52, respectively. FC levels returned to normal in 44% and 54% of patients at weeks 26 and 52, and CRP returned to normal in 36% and 37% of patients at weeks 26 and 52, respectively. AEs were recorded in 60 patients. The use of fewer previous anti‐TNFα agents and ileal localisation were associated with clinical remission, and endoscopic severity was associated with poor response. No factors correlated with endoscopic remission. Conclusion After 52 weeks, ustekinumab demonstrated effectiveness in inducing clinical and endoscopic remission in patients with refractory CD.

A nationwide real-world study on dynamic ustekinumab dosing and concomitant medication use among Crohn’s disease patients in Finland

“…This is a considerably higher proportion likely due to a more diseaserefractory patient population when compared to the patients of IM-UNITI trial where only 23% needed dose adjustment from q12w to q8w [21]. Our data on dosing patterns support the findings of other real-world registry studies of ustekinumab maintenance treatment where the majority or all the patients commenced their ustekinumab maintenance therapy with q8w dosing [6,10,12,13,22]. Interestingly, data on recapturing or improvement of ustekinumab response in CD patients with q4w dosing is emerging [11,[22][23][24][25].…”

“…However, some recent studies report clinical outcomes derived from specific real-world cohorts consisting of only dose optimized patients [11,[23][24][25]. Where reported, 22-52% of patients needed dose intensification, which appeared successful in around half of the patients [10,11,[22][23][24][25].In the present study, one-third of patients on ustekinumab maintenance therapy required dose intensification. Among patients initiating maintenance therapy with q12w dosing, two-thirds shortened the interval.…”

“…These proportions are slightly less compared to the proportion reported in IM-UNITI long-term extension where 35.4% of patients on q8w dosing were taking concomitant immunosuppressants through 92 weeks [37]. Iborra et al report that 28% of the patients who were using concomitant immunosuppressants at baseline were able to discontinue them completely during the follow-up, although these data were not stratified based on dose intensification status [10]. It is important also in refractory CD patients to achieve comparable treatment efficacy with biological monotherapies as with combination therapies because potential adverse effects of thiopurines are well known.…”

“…While the analysis of dosing patterns in IM-UNITI trial suggested regaining clinical response in 55% of patients following dose intensification from q12w to q8w [3,21], data on dose optimization in real-world situations remains scarce [10,22]. However, some recent studies report clinical outcomes derived from specific real-world cohorts consisting of only dose optimized patients [11,[23][24][25].…”

“…Furthermore, the patients have typically experienced several drug switches due to primary or secondary loss of response or intolerance [2]. While ustekinumab real-world studies have shown clinical benefit even in treatment-refractory CD patient cohorts, data on dosing patterns and dose optimization remain limited [6][7][8][9][10][11][12][13].…”