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

ABSTRACT: BACKGROUND:Evidence remains contradictory regarding second-line therapy in patients with Kawasaki disease (KD) refractory to initial intravenous immunoglobulin (IVIg). The objective of this study aims to evaluate the efficacy and safety of three treatments [i.e. a second IVIg infusion, methylprednisolone (IVMP), and infliximab (IFX)] in patients with refractory KD. METHODS:A systematic search of PubMed, Embase, Cochrane, and ClinicalTrials.gov using predefined MeSH terms was performed from 1990 through 2017. Relevance screening was performed by two independent reviewers. Inclusion criteria included English-only, original clinical data. Eight studies met the inclusion criteria. Fever resolution, coronary lesions, and adverse event outcomes were extracted and pooled for analysis. RESULTS:Of the 388 patients included from the 8 studies analyzed, a majority received a second IVIg dose (n?=?263, 68%). Fever resolution was comparable between IVIg (72%) and IVMP (73%). IFX (88%) significantly increased fever resolution by approximately 20% compared to IVIg re-dose (RR 1.2; [95% CI: 1.1-1.4]; p?=?0.03) and IVMP (RR 1.2; [95% CI: 1.0-1.5]; p?=?0.04). Clinical significance of differences in coronary outcomes remains unclear. CONCLUSIONS:This combined analysis was limited due to variability in design and data reporting methods between the studies and risk of bias. In the absence of a clinical trial, IFX monotherapy as second-line treatment should be considered in patients who fail to respond to initial IVIg. This conclusion is based on a systematic review of the literature with pooled outcome data analysis suggesting IFX is more effective in fever resolution compared to a second IVIg dose and IVMP.

SUBMITTER: Crayne CB

PROVIDER: S-EPMC6882052 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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

Crayne Courtney B CB Mitchell Chace C Beukelman Timothy T

Pediatric rheumatology online journal 20191127 1

<h4>Background</h4>Evidence remains contradictory regarding second-line therapy in patients with Kawasaki disease (KD) refractory to initial intravenous immunoglobulin (IVIg). The objective of this study aims to evaluate the efficacy and safety of three treatments [i.e. a second IVIg infusion, methylprednisolone (IVMP), and infliximab (IFX)] in patients with refractory KD.<h4>Methods</h4>A systematic search of PubMed, Embase, Cochrane, and ClinicalTrials.gov using predefined MeSH terms was perfo ...[more]

PMID: 31775898

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Project description:BackgroundThere 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.MethodsPubMed, 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.ResultsTwelve 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).ConclusionsInfliximab, 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 registrationThe study has been registered on PROSPERO ( CRD42016039693 ).

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

Publications

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

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