Indirect-comparison meta-analysis of treatment options for patients with refractory Kawasaki disease

Abstract

Background There is limited information available regarding the clinical management of intravenous immunoglobulin-resistant Kawasaki disease (KD). We aimed to evaluate the optimal treatment options for patients with refractory KD by presenting an indirect-comparison meta-analysis. Methods PubMed, EMBASE, Web of Science, and the Cochrane Database were searched on August 31, 2018. Unpublished studies were also searched in ProQuest Dissertations & Theses and through manual retrieval strategies. Randomized concurrent controlled trials (RCTs), high-quality non-randomized concurrent controlled trials (non-RCTs), and retrospective studies associated with AEs were included. The quality of all eligible studies was assessed using Cochrane collaboration’s tool and non-randomized study guidelines. Risk ratios (RR) with 95% confidence intervals (CIs) for dichotomous outcomes were estimated in our analysis. GRADE profiler 3.6.1 was used to assess the evidence profile. Results Twelve studies involving 372 immunoglobulin-resistant KD patients were identified and analyzed. Neither infliximab nor intravenous pulse methylprednisolone (IVMP) was significantly more effective than second IVIG infusion with respect to lowering coronary artery lesions (CALs) (infliximab, 0.85, 0.43–1.69; IVMP, 0.99, 0.52–1.88) and treatment resistance (infliximab, 0.43, 0.21–0.89; IVMP, 1.16, 0.33–4.13). No significant differences were found between infliximab and IVMP in the incidence rate of CALs (0.70, 0.27–1.81), the treatment resistance (0.37, 0.09–1.60), the rates of coronary artery aneurysm (4.13, 0.38–45.22) and the coronary artery dilatation (0.45, 0.10–1.99). Furthermore, compared with second IVIG infusion, both infliximab and IVMP showed significant effectiveness in antipyretic effects (infliximab, 1.52, 1.16–1.99; IVMP, 1.29, 0.77–2.15). However, Infliximab was noninferior to IVMP on antipyretic effects (1.18, 0.66–2.15). IVMP treatment showed significant association with fewer AEs than second IVIG infusion (0.49, 0.26–0.94) and infliximab (2.34, 1.07–5.09). No significant differences were noted between infliximab treatment and second IVIG infusion (1.06, 0.69–1.63). Conclusions Infliximab, IVMP, and second IVIG infusion showed no significant differences in the cardioprotective effect or the rate of treatment resistance. Infliximab and IVMP treatment were more effective than second IVIG infusion regarding antipyretic effects. IVMP treatment may have an advantage due to its lower total rate of AEs associated with drug infusion. Trial registration The study has been registered on PROSPERO ( CRD42016039693 ). Electronic supplementary material The online version of this article (10.1186/s12887-019-1504-9) contains supplementary material, which is available to authorized users.

Is there an association between intravenous immunoglobulin resistance and coronary artery lesion in Kawasaki disease?—Current evidence based on a meta-analysis

“…However, KD patients who fail to respond to 2 doses of IVIG present a unique challenge [ 80 ]. A meta-analysis comprising 372 refractory KD patients conducted in 2019 by Chan et al [ 81 ] revealed that infliximab, MP, and second IVIG infusion showed no significant differences in the cardioprotective effect or the rate of treatment resistance. So far, there is still no accepted treatment algorithm for refractory KD patients [ 82 ].…”

Low-Dose Prednisone Treatment for IVIG-Resistant Kawasaki Disease with Severe Arthritis and Joint Effusion in Two 3-Year-Old Children

“…Rather, low-dose prednisone managed the symptoms well. It has been reported that by comparing with a second IVIG infusion, infliximab and intravenous methylprednisolone (IVMP) were more effective in terms of antipyretic effects [ 6 ]. We propose here that, for the IVIG-resistant KD, longer period of low-dose corticosteroids may be a better treatment option instead of a second dose of IVIG.…”

Comparison of second-line therapy in IVIg-refractory Kawasaki disease: a systematic review

“…Seven of the studies included in this study were also included in the Chan et al meta-analysis. The differences in results are likely due to the variations in methodology [18].…”