Comparative Efficacy and Recurrence of Combination Therapies in Keloid Management: A Systematic Review and Network Meta-analysis

Abstract

Background: Combination therapies are increasingly recognized in keloid management, which has been challenging due to high recurrence and variable individual responses. This Network Meta-Analysis (NMA) aimed to identify the most effective combinations with the lowest recurrence rates.

Methods: The protocol was registered in PROSPERO (CRD42024594922). Relevant Randomized Controlled Trials (RCT) evaluating all combination therapies for keloid were extracted from Cochrane, PubMed, and Scopus, until January 7, 2025.

Results: A total of 1398 cases from 22 RCTs comparing different treatment combinations for keloid were included. The NMA revealed that only combinations involving Triamcinolone Acetonide (TAC) and 5-Fluorouracil (5-FU) displayed significantly higher efficacy than TAC monotherapy: TAC + 5-FU + Pulsed Dye Laser (PDL) (RR 2.98; 95% CI: 1.26 to 7.02) and TAC + 5-FU (RR 1.43; 95% CI: 1.05 to 1.93). The lowest recurrence rates were found in TAC + bleomycin (RR 0.04; 95% CI: 0.00 to 0.84) and TAC + 5-FU + brachytherapy (RR 0.23; 95% CI: 0.07 to 0.73). No other combinations showed statistically significant differences. Funnel plot analysis revealed no publication bias.

Conclusions: Combination therapies, particularly TAC + 5-FU with PDL or brachytherapy, and TAC + bleomycin, outperform TAC alone in efficacy and recurrence reduction. These findings support tailored, multimodal approaches for optimal keloid management and improved patient outcomes.

Fig. 1.

PRISMA flow diagram: overview of the study selection process. PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-analyses.

Fig. 2.

Network plot of studies of efficacy. The size of the nodes and the line thickness represent the number of studies that analyzed an intervention and compared 2 given interventions, respectively.

Fig. 3.

Forest plot for the pairwise comparison of the therapeutic efficacy. This graph shows that only interventions involving TAC + 5-FU combinations are significantly better than TAC injection alone (TAC + 5-FU + PDL and TAC + 5-FU).

Fig. 4.

RRs for therapeutic efficacy.

Fig. 5.

Funnel plot of the included efficacy studies.

Fig. 6.

SUCRA diagram displaying predicted ranking by therapeutic efficacy. Cumulative ranking curves nearer the top left and higher SUCRA values indicate better performance, whereas the radial SUCRA’s size of nodes represents the number of participants, and the line thickness indicates the number of trials conducted.

Fig. 7.

Network plot of studies of recurrence. The size of the nodes and the line thickness represent the number of studies that analyzed an intervention and compared 2 given interventions, respectively.

Fig. 8.

Forest plot for the pairwise comparison of the recurrence. This graph demonstrates that TAC + bleomycin and TAC + 5-FU + brachytherapy result in significantly lower recurrence than TAC monotherapy.

Fig. 9.

RRs for recurrence.

Fig. 10.

Funnel plot of the included studies of recurrence.

Fig. 11.

SUCRA diagram displaying predicted ranking by recurrence. Cumulative ranking curves nearer the top left and higher SUCRA values indicate lower recurrence; the size of nodes represents the number of participants, and the line thickness indicates the number of trials conducted.