Biological agents or small molecule dual therapy: a new strategy for the treatment of "refractory inflammatory bowel disease" | Research Express

Introduction The effective biological agents currently approved for the treatment of Crohn’s disease (CD) and ulcerative colitis (UC) include anti-tumor necrosis factor (TNF)-α, anti-α4β7 integrin, and anti-interleukin (IL) -12 and IL-23.

Tofacitinib is currently the only small molecule therapeutic drug approved for the induction and maintenance of moderate to severe UC.

The safety of new biologics seems to be higher than that of immunomodulators.

Therefore, the new treatment strategy is to use two biological agents at the same time or to combine biological agents and tofacitib in patients with refractory inflammatory bowel disease (IBD).

However, summary data on dual biologics or small molecule therapies is still lacking.

Therefore, Clin Gastroenterol Hepatol recently published a systematic review and meta-analysis aimed at evaluating the safety and effectiveness of dual biologic therapy or combination therapy with tofacitinib in patients with refractory IBD.

Study Introduction Through a systematic search of multiple electronic databases from the establishment of the database to November 9, 2020, cohort studies or case series evaluating the safety and effectiveness of dual biological agents or combination of biological agents and tofacitinib in the treatment of IBD patients are included Reported (>10 patients).

Use summary data to calculate the incidence of adverse events (AE), clinical remission rate and endoscopy remission rate.

The results of the study included a total of 30 studies, reporting 288 dual biologics or small molecule therapy trials in 279 patients (76% of them were CD patients; median treatment time was 24 weeks (IQR25-IQR75 13-32) ].

Dual therapy is mainly suitable for patients with drug-refractory IBD (81%) and patients with extraintestinal manifestations (EIM) or rheumatism (12%).

The most common dual treatment combinations include anti-TNF-α and anti-integrin (48% of all trials), Uselnumab and anti-integrin (19% of all trials).

During a median follow-up of 32 weeks (IQR25-IQR75 24-52), the combined incidence of AEs and serious adverse events was 31% (95%CI 13%-54%) and 6.
5% (95%CI 2.
1%-13.
1) %); clinical and endoscopy combined remission rates were 59% (95% CI 42%-74%) and 34% (95% CI 23%-46%) (Table 1).

Table 1 Meta-analysis results 12% (95% CI 4%-24%) of patients require surgery.

Patients receiving dual treatment due to concurrent EIM have a higher surgical success rate.

Heterogeneity of endoscopy response rate (p=0.
88, I2=0%), endoscopic remission rate (p=0.
44, I2=0%) and incidence of malignant tumors (p=0.
87, I2=0%) Not significant, but there is significant heterogeneity in other outcomes.

Conclusion For patients with highly selective refractory IBD, dual biologics or small molecule therapy may be a feasible treatment.

Before this method can be used more widely, it is necessary to explore a better treatment combination that can significantly improve the quality of the data.

Literature index: Ahmed W, Galati J, Kumar A, et al.
Dual Biologic or Small Molecule Therapy for Treatment of Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis[J].
Clin Gastroenterol Hepatol.
2021 Mar 30:S1542-3565 (21)00344-X.
Contribution email: tougao@medlive.
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