Efficacy of biologic agents in improving the Health Assessme(5)

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

Table I. Characteristics of included studies.

Study Anti-TNF: Adalimumab: Bejarano et al. (18)

Breedveld et al. (PREMIER) (19) Van de Putte et al. (20)

Weinblatt et al. (ARMADA) (21) Keystone et al. (22) Miyasaka et al. (CHANGE) (23) Kim et al. (24)

Total Age Disease Previous* number (years) duration treatment

(years) 148 47 0.75 MTX-naïve 799 52 0.7 MTX-naïve 544 53 11 DMARD 271 56 12 DMARD

619 56 11 DMARD 352 56 7 DMARD 128 49 7 DMARD 982 52 6 DMARD 619 52 6 DMARD 220 54 10 DMARD 542 51 0.75 MTX-naïve 234 52 12 DMARD 89 50 13 DMARD 254 51 7 DMARD 444 50 8 DMARD 508 54 0.5 DMARD-naïve 428 53 8 DMARD

652 51 9 DMARD 339 55 10 DMARD 1450 52 10 DMARD 391 53 12 Anti-TNF

755 48 1 MTX-naïve 520 53 12 Anti-TNF 465 51 10 Anti-TNF

673 51 6 DMARD 623 51 7 DMARD 1220 53 10 DMARD 499 53 12 Anti-TNF

Baseline Follow-up Jadad

HAQ (months) score

1.3 12 51.5 12 41.9 6 31.6 6 31.9 12 31.6 6 31.3 6 2 1.7 12 31.6 6 31.5 6 4 1.7 12 41.7 6 41.5 6 41.7 6 3 1.4 12 5 1.4 12 31.7 6 4 1.7 6 51.0 6 51.5 12 21.8 6 2 1.8 12 51.9 6 31.8 6 2 1.6 6 31.6 6 41.5 6 31.7 6 4

Certolizumab:

Keystone et al. (RAPID1) (25) Smolen et al. (RAPID2) (26)

Fleischmann et al. (FAST4WARD) (27) Etanercept: Emery et al. (COMET) (28) Moreland et al. (29) Weinblatt et al. (30) Combe et al. (31)

Golimumab:

Keystone et al. (GO-FORWARD) (32) Infliximab:

Goekoop-Ruiterman et al. (BeSt) (33) Maini et al. (ATTRACT) (34) Anti-CTLA4: Abatacept: Kremer et al. (AIM) (35) Kremer et al. (36)

Weinblatt et al. (ASSURE) (37) Westhovens et al. (ATTAIN) (38) Anti-CD20: Rituximab: Tak et al. (IMAGE) (39) Cohen et al. (REFLEX) (40) Emery et al. (DANCER) (41) Anti-IL-6 Tocilizumab:

Jones et al. (AMBITION) (42) Smolen et al. (OPTION) (43) Genovese et al. (TOWARD) (44) Emery et al. (RADIATE) (45)

*All MTX-naïve and DMARD-naïve populations were also biologic-naïve; MTX-naïve populations included patients treated with other DMARDs

Exposure to previous biologic <10%. HAQ: Health Assessment Questionnaire; MTX: methotrexate; DMARD: disease-modifying anti-rheumatic drug.

for some subjects the lower doses were suboptimal, this could have underesti-mated the effect of infliximab on HAQ. Subgroup analysis of the different in-fliximab doses was conducted and we did not find a difference, but the sample size was small (data not shown).

The other anti-TNF agents were not significantly different in improving HAQ in DMARD failures. A recently published meta-analysis by Schmitz et al. (6) found that etanercept was supe-rior to adalimumab at improving HAQ. Results of meta-analyses may vary de-pending on inclusion criteria, analyses used and the outcome selected. Our re-sults may also differ because Schmitz et al. used a Bayesian approach and a dif-ferent outcome for HAQ: % change in HAQ to account for variations in base-line HAQ values. We used meta-regres-sion and did not find that baseline HAQ affected our outcome of interest. Simi-lar to Shmitz et al., we found no benefit

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of certolizumab over other anti-TNF agents for HAQ improvement (6). Oth-er studies demonstrated an increased likelihood of achieving ACR20/50 re-sponses with certolizumab (7, 9, 11, 12). Two of the certolizumab trials had a different study design where patients who did not achieve an ACR20 at 12 weeks were considered non-respond-ers and were withdrawn from the trial, which could overestimate the effect of active treatment. In contrast, some tri-

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