Efficacy of biologic agents in improving the Health Assessme(7)

Efficacy of biologic agents in improving the Health Assessment Questionnaire (HAQ) score in established and early rheumatoid arthritis a meta-analysis with indirect comparisons

Fig. 4. Difference in mean change in HAQ in DMARD-naive or MTX-naïve patients with biologic agents compared to control.

In the anti-TNF-failure group, all drugs showed benefit compared to the control group, which met MCID. A small num-ber of studies included patients with ERA. Only one study investigating in-fliximab had no previous exposure to DMARDs. Therefore, there is insuffi-cient evidence in support of the use of biologic therapies in DMARD-naïve pa-tients for HAQ improvement. For MTX-naïve ERA trials, where patients were ex-posed to other DMARDs (predominate-ly sulfasalazine), the different biologics (adalimumab, etanercept and rituximab) were equally efficacious at improving HAQ compared to control. Mean dif-ference in change in HAQ was -0.23 for biologics compared to DMARD, which was similar to the studies investigating DMARD-failures in established RA. Patients in these ERA studies had failed at least 1 DMARD and had similar age and baseline HAQ to the patients in the DMARD-failure established RA group. The ERA studies in this meta-analysis represent a population of ERA patients with severe disease, which may explain why the HAQ was not more modifiable in ERA studies.

Indirect comparisons using meta-anal-ysis have several limitations. Although data are from RCTs, comparative analyses can be considered observa-tional studies and subject to biases and confounders. We have tried to reduce biases by selecting subgroup analyses and the outcome of interest a priori. We accounted for possible sources of heterogeneity including patient age, disease duration, baseline HAQ, drug doses, follow-up time, co-intervention, percentage of cross-over from control to intervention arms, publication date and Jadad score. By subgroup analyses

Table II. Subgroup analyses on mean difference in change in HAQ for biologic therapies compared to control ( HAQB-HAQC).

Prior treatment failure: DMARD Anti-TNF

DMARD/MTX-naïve Co-interventionDMARD None Follow-up 6 months 12 months

Number of studies

19 4 5 23 5 19 9

HAQB-HAQC

(95% CI) -0.26 (-0.31, -0.22) -0.36 (-0.42, -0.30) -0.19 (-0.26, -0.13) -0.23 (-0.25,-0.21) -0.27 (-0.35, -0.19) -0.23 (-0.26, -0.21) -0.22 (-0.27, -0.18)

p-value I2 (%)between groups

0.001

0.987

0.1731

55.00058.687.265.628.5

or meta-regression, these variables were not found to affect the comparative change in HAQ. Nevertheless there are other potential sources of heterogeneity that we did not control for because of incomplete information. Also, some of the analyses included a small number of trials, which may have been underpow-ered to detect effects. Although we did not detect any publication bias, several RCT were excluded because of insuf-ficient information to determine change in HAQ.

In conclusion, biologics improve physi-cal function in established RA patients failing DMARDs and anti-TNF agents. The mean improvement in HAQ at 6-12 months follow-up compared to DMARDs is at least the minimally clini-cally important difference for HAQ of 0.22. The role of biologic agents in im-proving HAQ in DMARD/methotrexate-naïve ERA is unclear. In the absence of head-to-head randomised controlled tri-als comparing biologic agents, compara-tive meta-analysis provides a means for examining differences in biologic effi-cacy. We found that in anti-TNF failures, the included biologics (abatacept, tocili-zumab and rituximab) appeared equally efficacious. In DMARD-failures, there were differences in HAQ reduction for some biologics. These differences should be interpreted in the context of the doses used, the populations studied and the design of the included studies. Future studies should confirm the differ-ences with head-to-head comparisons.

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