Li X, Tang Y, Ding Y, Chen Y, Hou M, Sun L, Qian G, Qin L, Lv H. Eur J Pharmacol. 2021 Feb 27;899:173985. doi: 10.1016/j.ejphar.2021.173985. Online ahead of print. PMID: 33652059
Take Home Points:
- Infliximab was more effective than the control group, with the total summary odds ratio (OR) of 0.34 (95% confidence interval (CI): 0.19–0.62). The treatment resistance of the infliximab group was lower than the IVIG group (0.36 [95% CI: 0.14–0.92]) when infliximab was combined with IVIG as the initial treatment.
- Infliximab treatment for IVIG resistant KD was more effective than the IVIG group (0.28 [95% CI: 0.12–0.66]). Infliximab improved clinical course in IVIG resistant KD patients.
- Infliximab treatment did not reduce the incidence of coronary artery lesions and did not show any significant increase in the incidence of adverse events.
Commentary from Dr. Manoj Gupta (New York, USA), section editor of Pediatric & Fetal Cardiology Journal Watch:
Kawasaki disease (KD) is a systemic immune vasculitis disease affecting the small and medium arteries. Coronary artery lesions (CALs) are one of the most severe complications in KD patients. A high dose of intravenous immunoglobulin (IVIG) is the mainstream treatment of KD. However, about 10–20% of KD patients show resistance to IVIG treatment. A good number of studies in recent days have shown that infliximab could be an effective treatment for IVIG-resistant KD.
This is a meta-analysis for the comprehensive evaluation of infliximab’s efficacy and safety as initial therapy for patients with KD and IVIG resistant KD by including both prospective and high-quality retrospective studies. Eight studies were included in this meta-analysis study. These studies covered 713 patients, with 327 cases in the infliximab treated group and 386 in the control group.
Effective of infliximab on KD
The total summary OR was 0.34 (95% CI: 0.19 to 0.62) with low heterogeneity (I2 = 30.1%), which showed that infliximab was more effective than the control group. The summary OR of infliximab treatment of IVIG resistant group was 0.28 (95% CI: 0.12 to 0.66), with low heterogeneity (I2 = 0). The results revealed that infliximab treatment was as effective as the initial treatment of KD as well as for IVIG resistant KD.
Coronary artery lesions (CAL)
Six studies reported the CALs complication. The summary OR of infliximab treatment on the IVIG resistant group was 0.88 (95% CI: 0.48 to 1.62), with low heterogeneity (I2 = 0). The summary OR was 0.64 (95% CI: 0.23 to 1.74) for infliximab as initial treatment group, with low heterogeneity (I2 = 0), the summary OR of infliximab as treatment of IVIG resistant group was 1.06 (95% CI: 0.49 to 2.28), with low heterogeneity (I2 = 7.9)
Adverse events (AEs)
Six studies reported the AEs. Analysis revealed that the incidence of AEs between both groups was not significant. The summary OR was 0.71 (95% CI: 0.44 to 1.16), with low heterogeneity (I2 = 45.3%
Infusion reaction was regarded as fever with or without chill requiring transient interruption of infusion. The results showed that the infusion reaction incidence in the infliximab group was significantly lower compared to the IVIG group. The summary OR was 0.11 (95% CI: 0.03 to 0.43), with low heterogeneity (I2 = 0).
Other adverse events
Patients treated with infliximab had a prevalence of transient hepatomegaly of 19% (6/31) versus 1.5% (1/68) in patients who never received infliximab, with an odds ratio of 16.1 (95% CI, 1.8 to 140.3; P = 0 0.004).
A: Comparison of treatment effectiveness between the infliximab group and control group
B: Comparing the treatment effectiveness of infliximab between prospective and retrospective studies, in the retreatment group.
The meta-analysis demonstrated that infliximab, a TNF-α blocker is useful either as a first-line treatment in KD or as a treatment for IVIG resistant KD.
This analysis has shown that infliximab is potently effective in reducing fever; however, it failed to reduce CALs. Infliximab might also increase the risk of TB and hepatitis when infection occurred. Nevertheless, physicians need to confirm the absence of TB lesions before the use of infliximab.
It is highly recommended that pediatricians consider early use of infliximab in cases with refractory KD due to its safety and efficacy.
When infliximab combined with IVIG had been used in the primal treatment of patients with KD, it could reduce the rate of resistance compared with conventional IVIG therapy. However, there was no advantage of reducing the incidence of the coronary artery lesions. Infliximab can improve treatment efficiency in treating children resistant to IVIG. There was no increase in adverse events in the treatment of infliximab. Infliximab might reduce the infusion reaction of IVIG. When patients with IVIG contraindicated or exhibited IVIG resistance, infliximab might be useful.