Head-to-head studies comparing biological DMARDs to other biological DMARDs
| Population | Study | Risk of bias | Treatment | n | Primary endpoint | Result | P / 95% CI | ACR20 (%) | ACR50 (%) | DAS28≤3.2 (%) | DAS28<2.6 (%) | CDAI≤2.8 (%) | ΔHAQ |
| csDMARD naïve early RA | Hetland 2020 (NORD-STAR)32 | High (single-blinded) | GC+MTX/ SSZ + HCQ + GC i.a.+MTX | 200 | Adjusted difference of CDAI ≤2.8 (week 24) | – | Reference | 127 (71.3) | 84 (47.2) | ||||
| CZP 200 mg Q2W+MTX | 203 | 3.9 | −5.5 to 13.2 | 139 (77.2) | 97 (53.9) | ||||||||
| ABA 125 mg QW+MTX | 204 | 9.4 | 0.1 to 18.7 | 142 (74) | 107 (55.4) | ||||||||
| TCZ 8 mg/kg Q4W or TCZ 162 mg QW+MTX | 188 | −0.6 | −10.1 to 8.9 | 119 (73) | 77 (46.7) | ||||||||
| MTX-IR | Feist ACR 2021 / Smolen 2022 (CREDO 2)29 30 | Low | Placebo+MTX | 243 | ACR20 (week 12) | 108 (44.4) | – | 108 (44.4) | 55 (22.6)* | 31 (12.8) | 148 (31.9) * | 10 (4.1)* | −0.42* |
| OKZ 64 mg Q2W+MTX | 464 | 326 (70.3) | 0.034 | 326 (70.3) | 234 (50.4)* | 210 (45.3) | 168 (35.1) * | 52 (11.2)* | −0.64* | ||||
| OKZ 64 mg Q4W+MTX | 479 | 342 (71.4) | 0.045 | 342 (71.4) | 240 (50.1)* | 219 (45.7) | 132 (28.6) * | 58 (12.1)* | −0.61* | ||||
| ADA 40 mg Q2W+MTX | 462 | 309 (66.9) | Reference | 309 (66.9) | 214 (46.3)* | 177 (38.3) | 26 (10.7)* | 60 (13.0)* | −0.61* | ||||
| TNF-IR (B-cell poor based on histology) | Humby 2021 (R4RA)31 | High (open-label) | B-cell poor: RTX 1000 mg (d1, d15) + csDMARDs | 38 | CDAI50% response (week 16) | 17 (45%) | Reference | 12 (32%) | 7 (18) | −0.3±0.1 | |||
| B-cell poor: TCZ 8 mg/kg Q4W+csDMARDs | 41 | 23 (56%) | 0.31 | 19 (46%) | 13 (32) | −0.4±0.1 |
Results of secondary efficacy outcomes are shown at the timepoint of the primary endpoint.
*Week 24.
ABA, abatacept; ACR, American College of Rheumatology; ADA, adalimumab; CDAI, Clinical Disease Activity Index ; csDMARD, conventional synthetic DMARD; CZP, certolizumab-pegol; DMARD, disease-modifying antirheumatic drug; GC, glucocorticoids; HAQ, health assessment questionnaire; HCQ, hydroxychloroquine; i.a., intra-articular; IR, insufficient response; MTX, methotrexate; OKZ, olokizumab; PBO, placebo; QW, weekly; Q2W, every 2 weeks; Q4W, every 4 weeks; RTX, rituximab; SSZ, sulfasalazine; TCZ, tocilizumab; TNF, tumour necrosis factor alpha.