Thirty randomised controlled trials (RCTs; n=3,975; 77 treatment arms) were included in the review. Sample sizes ranged from 11 to 1,100 patients.
Twelve studies reported adequate allocation generation, six reported adequate allocation concealment and only two were double-blind, with the remainder being open-label.
Tetracycline-streptomycin versus tetracycline-rifampicin (13 studies): overall failure was significantly higher in patients receiving tetracycline-rifampicin (RR 2.30, 95% CI: 1.65, 3.21, p<0.001), with the main difference originating from differences in relapse rates (RR 2.86, 95% CI: 1.84, 4.43, p<0.001), which translates into a number-needed-to-treat of 11 (95% CI: 8 to 17) with tetracycline-streptomycin to prevent one relapse after treatment with tetracycline-rifampicin. There were no significant differences between groups for therapeutic failure.
Quinolone versus non-quinolone-based regimen (5 studies): overall failure was significantly higher in patients receiving any quinolone regimen compared with those without quinolone (RR 1.83, 95% CI: 1.11, 3.02, p<0.02). Two studies comparing quinolone-rifampicin with doxycycline-streptomycin reported greater overall failure in the quinolone group (RR 2.28, 95% CI: 1.17, 4.46). However, heterogeneity was reported.
Monotherapy versus combination treatment (7 studies): significant heterogeneity was evident among studies comparing monotherapy with combination treatment regimens, thus meta-analysis could not be performed. Separate analyses by type of monotherapy showed mixed results.
Short- versus long-term treatment (6 studies): 4 studies reported significantly higher overall failure, therapeutic failure and relapse with shorter treatment durations; the RRs were 3.08 (95% CI: 1.01, 9.38, p=0.07), 3.02 (95% CI: 1.03, 8.80) and 1.70 (95% CI: 1.19, 2.44), respectively. There were no significant differences in primary outcomes when using short duration doxycycline-streptomycin compared with long duration doxycycline-rifampicin (4 studies). Several analyses showed significant heterogeneity. Two studies reported significantly higher overall failure in short duration doxycycline-streptomycin compared with long duration tetracycline-streptomycin (RR 6.25, 95% CI: 2.44, 16.7).
The results for secondary outcomes were also reported in the review. For other comparisons (10 studies) where the number of trials were limited or the results non significant, secondary outcomes and sensitivity analyses were also reported.
Selection bias was not evident from the funnel plot analysis for overall failure and relapse, but no data were presented.