Dose Escalation Patterns of Advanced Therapies in Crohn’s Disease and Ulcerative Colitis: A Systematic Literature Review

Abstract

Introduction Dose escalation is one of the treatment approaches studied and suggested in advanced therapies for Crohn’s disease (CD) and ulcerative colitis (UC). This study aimed to identify and characterize the dosing escalation patterns of advanced therapies in CD and UC. Methods Two systematic literature reviews (SLRs) were conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE ® , Embase ® , and Cochrane Library were searched for articles published between January 2011 and October 2021 and limited to non-interventional studies in English language. Congress and bibliographic searches were also conducted. Articles were screened by two independent researchers. Dose escalation patterns were described and summarized considering the regional regulatory label recommendation (in North America [NA] or outside of North America [ONA]). Results Among 3190 CD and 2116 UC articles identified in the Ovid searches, 100 CD and 54 UC studies were included in the SLR, with more studies conducted ONA. Most studies reported an initial maintenance dose pattern aligned with the lower starting dose per local regulatory label; however, several ONA studies ( n = 13 out of 14) reported ustekinumab every 8 weeks as starting maintenance pattern in CD. In ONA studies, the median within-guideline escalation rates in CD and UC were 43% in ustekinumab (CD only), 33% and 32% for vedolizumab; 29% and 39% for adalimumab; and 14% and 10% for infliximab. Evidence regarding dose escalation patterns for tofacitinib, certolizumab pegol, and golimumab was limited. Some dose escalation patterns outside of label recommendations were observed including ustekinumab every 8 weeks to every 4 weeks and vedolizumab every 8 weeks to every 6 weeks. Conclusion Dose escalation strategies are widely documented in the literature. The reported dose escalation patterns and escalation rates vary by region and by CD and UC. Most escalation patterns reported were aligned with regulatory recommendations while some reported more diverse or aggressive dose escalation. Prospero Registration CRD42021289251. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-023-02457-6.

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

“…A recent systematic literature review supported our findings by indicating that ustekinumab with an initial regimen of 90 mg every 12 weeks had a dose intensification rate of 43% in patients with CD. 20 Furthermore, dose intensifications in CD patients were reported as 19% for first-line treatment and 37% for second-line treatment with increasing rates observed according to the line of treatment. 21 The consistency between our study results and the literature review underscores the robustness of the observed dose intensification patterns in the treatment of CD using ustekinumab.…”

Cost per Number Needed to Treat (NNT) for upadacitinib in the treatment of bio-exposed patients with moderately-severely active ulcerative rectocolitis

“…3 ) ( 14 ). Dal momento che è peso-dipendente, la dose di 390 mg somministrata per via endovenosa (IV) di UST durante l’induzione ( 11 ) è stata calcolata facendo riferimento a un paziente standard con un peso medio corporeo di 70 kg ( 22 ), mentre, nel mantenimento, è stato considerato lo schema posologico più utilizzato nella pratica clinica che prevede la somministrazione sottocute (SC) di UST 90 mg QW8 ( 11 , 18 , 23 , 24 ). Per vedolizumab, nella fase di induzione, è stata considerata la dose raccomandata di 300 mg somministrata mediante infusione endovenosa alle settimane 0, 2 e 6, mentre, nella fase di mantenimento, è stata considerata una dose raccomandata di 300 mg somministrata mediante infusione endovenosa ogni Q8W ( 10 ), anche se, nella pratica clinica, circa il 20-25% dei pazienti ricorre a una somministrazione ogni 4 settimane (Q4W) ( 25 , 26 ).…”