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
MTX-IR	Gabay et al (2013) (ADACTA)40	Superiority trial	High	TCZ 8 mg/kg Q4W	163	ΔDAS28-ESR at week 24	−3.3	<0.0001	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
MTX-IR	Burmester et al (2017) (MONARCH) 41	Superiority trial	High	SAR 200 mg Q2W	184	ΔDAS28-ESR at week 24	−3.28	<0.0001	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.