Characteristics of the studies included in the meta-analysis
| Study, year of publication | TNFi (dosage) | Dosage of MTX per trial arm, application route | Female (%), per trial arm | Age ±SD, years per trial arm | Blinding | Disease/symptom duration mean±SD, per trial arm at BL, months | Indicators of disease activity, per trial arm, mean ±SD | HAQ, mean±SD, per trial arm HAQ at BL±SD | Patients per trial arm | Added therapy (corticosteroids) |
|---|---|---|---|---|---|---|---|---|---|---|
| T20 2004 | Infliximab (3 mg/kg given at BL, 2 wks, 6 wks and at 8-wk intervals until 46 wks). | Both arms: 7.5 mg/wk at BL, 15 mg/wk at wk14 | Combo: 60 Mono: 60 | Combo: 51±10 Mono: 53±14 | 54 wks double-blinded, then observational | Combo: 6(3–12)*/7±5† Mono: 5(3–11)*/6±4† | DAS28-ESR by default Combo: 6 Mono: 7 | Combo: 1±1 Mono: 1±1 | Combo: 10 Mono:10 | Glucocorticoids were not permitted for the first 14 wks of study. Thereafter (intra-articular or intramuscular) glucocorticoids were permitted if clinically required (maximum dose: 120 mg methylprednisolone in 3-month study periods). |
| BeST 2005 | Infliximab (3 mg/kg, adjusted after 3 months depending on DAS) Infliximab was increased from 3, 6, 7.5 to 10 mg/kg over 8 wks if persistent DAS over LDA) | Combo: 25–30 mg/wk Mono:15 mg/wk (was increased if LDA) | Combo: 66 Mono: 68 | Combo: 54±14 Mono: 54±13 | Blinded joint assessors | Combo: median 0.5/6(3–12)* Mono: median 0.5/6(4–14)* | DAS44-ESR by default Combo: 4±1 Mono: 5±1 | Combo: 1±1 Mono: 1±1 | Combo: 128 Mono:126 | 22% received intra-articular glucocorticoid injections in mono, while 13% received it in combo. |
| GUEPARD 2009 | Adalimumab (40 mg eow) | Both arms: maximum 20 mg/wk, orally | Combo:79 Mono: 81 | Combo: 46 ±16 Mono: 49±15 | Not blinded | Combo: ≤6/4(3–5)* Mono: ≤6/4(3–5)* | DAS28-ESR by default Combo: 6±1 Mono: 6 ±1 | Combo: 2±1 Mono: 1±1 | Combo: 33 Mono: 32 | A single intra-articular glucocorticoid injection was allowed during the trial. |
| HIT HARD 2012 | Adalimumab (40 mg eow) | Both arms: 15 mg/wk, sc | Combo: 70 Mono: 67 | Combo: 47±12 Mono: 53±14 | Double-blinded | Combo: 2±2/<4 Mono: 2±2/<4 | DAS28-ESR by default Combo: 6(±1) Mono: 6(±1) | Combo: 1±1 Mono: 1±1 | Combo: 87 Mono: 85 | Maximum ≤10 mg/day prednisone |
| OPERA 2014 | Adalimumab (40 mg eow) | Both arms: maximum 20 mg/wk, orally | Combo: 63 Mono: 69 | Combo: 56 (26–78)* Mono: 54 (28–77)* | Double-blinded during 12 months | Combo: <3/not stated Mono: <3/not stated | DAS28-CRP Combo: 6(4–8)* Mono: 6(4–7)* | Combo: 1 (0.2–3)* Mono: 1 (0.2–2)* | Combo: 89 Mono: 91 | Swollen joints injected with triamcinolone when required |
| OPTIMA 2014 | Adalimumab (40 mg eow) | Both arms: maximum 20 mg/wk, orally | Combo: 73 Mono: 67 | Combo: 50±15 Mono: 49±13 | Double-blinded | Combo: 4(3)/not stated Mono: 4(3)/not stated | DAS28-CRP combo: 6±1 mono: 6±1 | Combo: 2 (1) † Mono: 1 (1)† | Combo: 515 Mono: 517 | Co-therapy with non-steroidal anti-inflammatory drugs, or prednisone or equivalent (≤10 mg/day), could continue at a stable dose for 4 wks or more before BL. |
*Median (IQR).
†Mean (SD).
BL, baseline; combo, combination arm; CRP, C reactive protein; DAS28, disease activity score by 28 joints; DAS44, disease activity score by 44 joints; ESR, erythrocyte sedimentation rate; HAQ, Health Assessment Questionnaire; LDA, low disease activity, eow, every other week; mono, MTX monotherapy arm; MTX, methotrexate; sc, subcutaneously; TNFi, tumour necrosis factor inhibitor; wk, week.