P1043 Immunomodulator and advanced therapies for prevention of clinical relapse and loss of response during maintenance phase in Crohn’s disease: A systematic review and network meta-analysis

Abstract

Background
Several effective advanced therapies have been approved for the treatment of Crohn’s disease (CD) in the past two decades. Given lack of adequate head-to head clinical trials it is challenging to position these therapies in the management algorithm. Therefore we performed this network meta-analysis to inform therapeutic decisions.

Methods
We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials between inception and October 2023 for randomised controlled trials (RCTs). Outcomes assessed were clinical relapse (loss of clinical remission), loss of clinical response, adverse events (AE), withdrawal due to AE, and serious AE. We performed random-effects meta-analysis and network meta-analysis (using a frequentist approach), and estimated relative risk (RRs), 95%CI values. We used GRADE to ascertain certainty of evidence.

Results
A total of 32 RCTs comprising 10,924 patients were included in the analysis. On network meta-analysis of 15 interventions based on prevention of clinical relapse, combination of infliximab (IFX) and azathioprine (AZA) (RR 0.31, 95%CI [0.17-0.56]), IFX (RR 0.62, 95%CI [0.5-0.76], moderate certainty), and adalimumab (RR 0.68, 95%CI [0.55-0.84], moderate certainty) were the only agents that were effective compared to placebo (Figure 1). Methotrexate (RR 0.57, 95%CI [0.32-1.03], low certainty) and azathioprine (RR 0.82, 95%CI [0.62-1.1]), very low certainty) were not effective. On analysis based on prevention of clinical response for nine interventions, there was high certainty evidence for ustekinumab (RR 0.73, 95%CI [0.61-0.86]), upadacitinib (RR 0.64, 95%CI [0.57-0.72]), and moderate certainty of evidence for infliximab (RR 0.71, 95%CI [0.59-0.84]), adalimumab (RR 0.68, 95%CI [0.61-0.75]), certolizumab (RR 0.57, 95%CI [0.47-0.7]), CTP13 (RR 0.46, 95%CI [0.38-0.57]), vedolizumab (RR 0.82, 95%CI [0.68-0.99]), natalizumab (RR 0.54, 95%CI [0.43-0.68]). Tofacitinib was not effective and there was no data available for immunomodulators and combination therapies for this outcome. On analysis of serious adverse events advanced therapies were of no difference to placebo (very low certainty).

Conclusion
On network meta-analysis immunomodulators and advanced therapies for maintenance phase, combination of anti-TNFs and immunomodulators followed by anti-TNF monotherapy had large effect size with moderate certainty for prevention of clinical relapse. There was moderate to high certainty evidence to suggest newer advanced therapies are effective in prevention of loss of clinical response.