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. 2023 Jul 28;83(13):1179–1205. doi: 10.1007/s40265-023-01916-2

Table 2.

Meta-analyses of studies evaluating the efficacy of anti-TNF agents for the prevention of postoperative recurrence in Crohn’s disease

Year of publication Author Main results Conclusions
2012 van Loo [99] Mesalamine is more effective in preventing clinical POR than placebo (p = 0.012), as well as nitro-imidazolic antibiotics (p < 0.001) and thiopurines (p = 0.018). Nitroimidazolic antibiotics (p = 0.037), thiopurines (p = 0.015) and infliximab (p = 0.006) are more effective than placebo in preventing endoscopic POR Mesalamine and infliximab seem to be superior to placebo in preventing clinical and endoscopic POR, respectively
2014 Nguyen [100] There was a higher frequency of clinical remission beyond one year from time of surgery among patients receiving anti–TNF therapy compared with conventional therapy (OR, 6.41; 95% CI, 2.9–14.3). There was also a significantly higher rate of both endoscopic (OR, 26.4; 95% CI, 10.5–66.7) and histologic remission (OR, 9.80; 95% CI, 2.54–37.81) in the anti-TNF therapy group compared with the conventional therapy group Anti-TNF therapy is more effective at preventing clinical, endoscopic, and histologic POR beyond one year from time of surgery compared with conventional therapy
2014 Yang [25] Fifteen trials involving 1507 patients were included in this analysis. Biological agents were associated with a significant reduction of both endoscopic and clinical POR compared with placebo, 5-aminosalicylates, or immunomodulators Biologics are the most effective medications to prevent CD POR
2015 Carla–Moreau [101] Nine controlled trials (n = 362) that evaluated the efficacy of anti-TNF therapy in preventing (n = 7) or treating (n = 2) POR were included. Anti–TNF therapy was more effective at preventing (n = 6) endoscopic POR than the control arms (OR, 0.05; 95% CI, 0.02–0.13). Anti-TNF therapy was more effective at preventing (n = 5) clinical POR than the control arms (OR, 0.10; 95% CI, 0.05–0.21). Anti-TNF therapy was more effective than control arms at treating endoscopic POR (n = 2; OR, 16.6; 95% CI, 2.51–110.3) Anti-TNF agents may be more effective in preventing clinical and endoscopic POR than control treatment (thiopurines or mesalamine)
2015 Zhao [102] Seven controlled trials met the inclusion criteria. At one-year post-operation, the biologic therapies showed significant preventive effects in clinical POR (RR, 0.36; 95% CI, 0.16–0.79), endoscopic POR (RR, 0.16; 95% CI, 0.07–0.34) and severe endoscopic POR (RR, 0.17; 95% CI, 0.04–0.71) when compared with the control arms. This advantage was confirmed at two years. The biological agents were more effective than azathioprine in preventing endoscopic POR (RR, 0.09; 95% CI, 0.02–0.47). Biologics were equally safe as controls Biologics are superior to azathioprine and traditional therapies and are not associated with increased adverse events in the postoperative treatment of CD
2015 Singh [26] Twenty-one trials, comprising 2006 participants comparing seven treatment strategies were included. On network meta–analysis, compared with placebo, mesalamine (RR, 0.60; 95% CI, 0.37–0.88), antibiotics (RR, 0.26; 95% CI, 0.08–0.61), immunomodulator monotherapy (RR, 0.36; 95% CI , 0.17–0.63), immunomodulators with antibiotics (RR, 0.11; 95% CI, 0.02–0.51), and anti-TNF monotherapy (RR, 0.04; 95% CI, 0.00–0.14), but not budesonide, reduced the risk of clinical POR. Likewise, compared with placebo, antibiotics (RR, 0.41; 95% CI, 0.15–0.92), immunomodulator monotherapy ( RR, 0.33; 95% CI, 0.13–0.68), immunomodulators with antibiotics (RR, 0.16; 95% CI, 0.04–0.48), and anti-TNF monotherapy (RR, 0.01; 95% CI, 0.00–0.05), but neither mesalamine nor budesonide, reduced the risk of endoscopic POR. Anti-TNF monotherapy was the most effective pharmacological intervention for POR prophylaxis (clinical POR: RR, 0.02–0.20; endoscopic POR: RR, 0.005–0.04) Based on Bayesian network meta–analysis combining direct and indirect treatment comparisons, anti-TNF monotherapy appears to be the most effective strategy for CD postoperative prophylaxis
2015 Qiu [103] Six prospective studies were included. The rate of endoscopic POR was significantly lower using anti-TNFs (9.2%, 7/76) compared with the non-biologics group (61.5%, 83/135) (OR, 0.05, 95% CI, 0.02–0.13). A significantly lower proportion of patients in the anti-TNFs group developed clinical POR (3.4%, 2/59) compared with the non-biologics arm (41.1%, 49/119; OR, 0.1). The adverse events were similar between the two groups (anti–TNFs 45% vs control 52%; p = 0.69) Anti-TNFs are superior to non–biological agents in preventing endoscopic and clinical POR without causing more adverse events
2017 Feng [104] Fourteen RCTs (877 participants) were included. Two strategies were superior to placebo for preventing endoscopic CD POR at one year after surgery: infliximab and adalimumab. Nine strategies were not effective, including budesonide, mesalazine, and azathioprine Except for infliximab and adalimumab, other strategies were not effective for preventing endoscopic CD POR
2018 Huang [105] A total of seven prospective trials were included in this meta–analysis (N = 455). Compared with the placebo group, infliximab decreased the rates of endoscopic POR (RR, 0.421; 95% CI, 0.328–0.539), and clinical POR in the infliximab-treated group (RR, 0.519; 95% CI, 0.349–0.774) Compared with controls, infliximab is a promising therapeutic agent for the management of POR in CD patients
2019 Burr [28] This network meta-analysis included 10 RCTs, containing 751 patients, in the primary analysis of endoscopic POR at 12 months. Anti-TNF therapies were significantly better than placebo, either alone (RR, 0.13; 95% CI, 0.04–0.39) or in combination with 5-aminosalicylates (RR, 0.30; 95% CI, 0.12–0.75), or 5-nitroimidazoles (RR, 0.40; 95% CI, 0.23–0.69) Anti-TNF therapies alone, or in combination, appear to be the best medications for preventing endoscopic POR
2019 Bakouny [106] In this network meta–analysis, the authors identified nine studies, including 571 patients and five treatment agents, among then two anti-TNF drugs (adalimumab and infliximab). Compared with infliximab, this network meta-analysis yielded the following results on the effect on endoscopic POR: adalimumab (OR, 0.92; 95% CI, 0.18–4.75), thiopurines (OR, 4.11; 95% CI, 0.68–24.8), placebo (OR, 4.39; 95% CI, 0.70–3.68), and mesalamine (OR, 37.8; 95% CI, 3.77–379.4) On the basis of a network meta–analysis combining direct and indirect evidence either adalimumab or infliximab may be used in the postoperative prophylaxis of CD POR
2019 Erős [107] Anti-TNF agents were significantly better in preventing clinical, endoscopic, severe endoscopic and histological POR compared to conventional therapies (OR, 0.508; 95% CI, 0.309–0.834; OR, 0.312; 95% CI, 0.199–0.380; OR, 0.195; 95% CI, 0.107–0.356; and OR, 0.255; 95% CI, 0.106–0.611, respectively). Infliximab and adalimumab proved to be equally effective Anti-TNF agents are more effective in preventing clinical, endoscopic, and histological POR than conventional therapies
2021 Jain [108] Twenty-four studies were included in the meta-analysis. The endoscopic, clinical, and surgical POR rates with the use of anti-TNF agents at one year were 21.7% (95% CI, 16.3–28.4%), 13.1% (95% CI, 8.2–18.9%) and 3.8% (95% CI, 1.4–9.9%), respectively. The 5-year POR rate was 84.2% (95% CI, 72.3–91.6%) and 17.5% (95% CI, 9.2–30.8%) for endoscopic and surgical POR, respectively. Subgroup analyses at one year for the type of anti-TNF agent or the timing of initiation after surgery showed no significant difference in endoscopic, clinical, and surgical POR Anti-TNF agents are effective at preventing clinical, endoscopic, and surgical POR. The timing of initiating biological therapy after surgery has no significant effect on POR. The efficacy of infliximab and adalimumab is similar
2021 Liu [12] Twenty-six studies (including 10 RCTs) with 2136 participants were included. Biologics were more efficient over non-biological treatments in preventing endoscopic, severe endoscopic, and clinical POR without increasing the frequency of adverse events. Anti-TNF agents were better than vedolizumab in preventing endoscopic POR. Moreover, infliximab had a similar curative effect to adalimumab in preventing endoscopic, severe endoscopic, and clinical POR Biologics, especially anti-TNF agents, still play a vital role in preventing POR
2021 Uchino [109] A total of 570 participants, including 254 patients in the intervention group and 316 patients in the control group, in 8 studies, were analysed for POR. The efficacies of anti‐TNF therapy at preventing endoscopic and clinical POR were as follows: RR, 0.34 (95% CI, 0.22–0.53); and RR, 0.60 (95% CI, 0.36–1.02), respectively. The RR of adverse event with anti‐TNF therapy was 1.75 (95% CI, 0.81–3.79) Anti‐TNF therapy displays efficacy at preventing endoscopic POR for 1–2 years, without increasing the incidence of adverse events. However, clinical POR is not significantly reduced
2022 Beelen [110] In this individual participant data meta-analysis, 645 CD participants from six studies were included. In the total population, a superior effect was demonstrated for anti-TNF compared with thiopurine prophylaxis for endoscopic POR (RR, 0.52; 95% CI, 0.33–0.80), clinical POR (RR, 0.50; 95% CI, 0.26–0.96), and severe endoscopic POR (RR, 0.41; 95% CI, 0.21–0.79) Anti-TNF agents are superior to thiopurine prophylaxis for the prevention of endoscopic and clinical POR after ileocolonic resection

CD Crohn’s disease, CI confidence interval, OR odds ratio, POR postoperative recurrence, RCT randomised clinical trial, RR relative risk