Table 1.
Head-to-head studies comparing bDMARDs specifically targeting IL-6 receptor or ligand to tumour necrosis factor alpha inhibitors
| Population | Study | Design | Risk of bias (RoB) | Treatment arm | No. of patients (n) | Primary endpoint | P value (primary endpoint) |
ACR20 (%) |
ACR50 (%) |
ACR70 (%) |
DAS28 <2.6 (%) |
CDAI≤2.8 (%) |
ACR/EULAR Boolean remission (%) | ΔHAQ (mean) | |
| MTX-IR | Gabay et al (2013) (ADACTA)40 | Superiority trial | High | ADA 40 mg Q2W | 162 | ΔDAS28-ESR at week 24 | −1.8 | <0.0001 | 49.4 | 27.8 | 17.9 | 10.5 | 9.3* | NR | −0.5 |
| TCZ 8 mg/kg Q4W | 163 | −3.3 | 65.0 | 47.2 | 32.5 | 39.9 | 17.2* | NR | −0.7 | ||||||
| MTX-IR | Burmester et al (2017) (MONARCH) 41 | Superiority trial | High | ADA 40 mg Q2W | 185 | ΔDAS28-ESR at week 24 | −2.2 | <0.0001 | 58.4 | 29.7 | 11.9 | 7.0 | 2.7 | NR | −0.43 |
| SAR 200 mg Q2W | 184 | −3.28 | 71.7 | 45.7 | 23.4 | 26.6 | 7.1 | NR | −0.61 | ||||||
| MTX-IR | Taylor et al (2018) (SIRROUND-H)42 | Superiority trial | High | ADA 40 mg Q2W | 186 | ΔDAS28-ESR+ACR 50 (%) at week 24 | −2.19 | Reference | 56.5 | 31.7 | 12.9 | 7.5 | NR | 3.8 | −0.52 |
| SRK 50 mg Q4W | 186 | −2.58 | 0.013 | 53.8 | 26.9 | 11.8 | 12.9 | NR | 3.8 | −0.51 | |||||
| SRK 100 mg Q2W | 187 | −2.96 | <0.001 | 58.8 | 35.3 | 15.5 | 20.3 | NR | 3.7 | −0.53 | |||||
| MTX-IR | Weinblatt et al (2015)44‡ | Dose-ranging study with active comparator (ADA) | Unclear | Placebo+MTX | 61 | ACR 20 (%) at week 12 | 39.3 | Reference | 37.7† | NR | 6.6† | 1.6 | 3.3 | 3.3 | −0.62† |
| ADA 40 mg Q2W+MTX | 59 | 76.3 | <0.05* | 66.1† | NR | 18.6† | 20.3 | 8.5 | 5.1 | −0.66† | |||||
| CLZ 25 mg Q4W+MTX | 59 | 76.3 | <0.05 | 81.4† | NR | 27.1† | 35.6 | 11.9 | 8.5 | −0.68† | |||||
| CLZ 100 mg Q4W+MTX | 60 | 73.3 | <0.05 | 65.0† | NR | 40.0† | 35.0 | 8.3 | 10.0 | −0.79† | |||||
| CLZ 200 mg Q4W+MTX | 60 | 60.0 | <0.05 | 66.7† | NR | 30.0† | 26.7 | 3.3 | 5.0 | −0.71† | |||||
| CLZ 100 mg Q4W+Placebo | 60 | 55.0 | <0.05 | 58.3† | NR | 16.7† | 21.7 | 8.3 | 6.7 | −0.64† | |||||
| CLZ 200 mg Q4W+Placebo | 59 | 61.0 | <0.05 | 57.6† | NR | 25.4† | 25.4 | 3.4 | 1.7 | −0.60† | |||||
Results of secondary efficacy outcomes are depicted at the time point of the primary endpoint. ADACTA-H, MONARCH-H and SIRROUND-H trial were judged as being at high RoB due to inclusion of acute phase reactants in the outcome of the primary endpoint.
*Posthoc analysis.
†Efficacy outcome at week 24.
‡Study not powered to compare CLZ with ADA.
ACR, American College of Rheumatology; ADA, adalimumab; CDAI, Clinical Disease Activity Index; CLZ, clazakizumab; DAS28, Disease Activity Score of 28 joints; ESR, erythrocyte sedimentation rate; HAQ, Health Assessment Questionnaire; MTX, methotrexate; NR, not reported; Q2W, every other week; Q4W, once every 4 weeks; SAR, sarilumab; SRK, sirukumab; TCZ, tocilizumab; Δ, change from baseline.