Table 4

Comparison of induction therapy with bDMARD±MTX followed by step-down and MTX monotherapy on clinical and radiographic outcomes in patients with early arthritis

Study (LoE)	Trial	Systematic bDMARD withdrawal	Withdrawal from	Population (DMARD naïve)	Initial therapy	Clinical outcome after step-down		Radiographic outcome after step-down		Risk of bias
Detert et al (1b)39	HIT HARD	Yes	Week 24	Pts with ERA n=87	ADA+MTX	DAS28 remission at week-48	42%	Week-48 mTSS	2.6	Low
			NA	n=85	MTX+PBO		37%		6.4*
Atsumi et al (1b)44	C-OPERA	Yes	Week 52	Pts with high risk† ERA n=108	CZP+MTX	SDAI remission at week 104	41%	Percentage of patients with year 2 ΔmTSS ≥0.5	16%	Unclear‡
			NA	n=71	MTX+PBO		29%*		32%***
Hørslev-Petersen et al (2b)45	OPERA	LDA only	Week 54	Pts with ERA n=89	ADA+MTX	DAS28CRP <2.6 at 24 months	69%	Per centage of pts with year 2 ΔmTSS ≥1	84%	Low
			NA	n=91	MTX+PBO		66%		80%
Smolen et al (2b)46	OPTIMA	LDA only	Week 26	Pts with ERA n=102	ADA+MTX	DAS28CRP <2.6 at 78 weeks	66%	Percentage of pts with week78 ΔmTSS ≥0.5	81%	Low
			NA	n=112	MTX+PBO		68%**		78%
Emery et al (2b)43	AVERT	LDA only	Week 54	Pts with ACPA+ERA n=119	ABA+MTX	DAS28-CRP <2.6 at 18 months	18%	None		Low
			Week 54	n=116	ABA+PBO		12%
			NA	n=116	MTX+PBO		9%*

p Value for comparison bDMARD+MTX versus MTX *<0.05; **<0.01; ***<0.001.
†High-risk ERA defined as high titres of ACPA/RF or erosions.
‡Abstract only.
ACPA, anticitrullinated protein antibody; ADA, adalimumab; CZP, certolizumab-pegol; DB, double-blind; ERA, early rheumatoid arthritis; LDA, low disease activity; LoE, level of evidence; MTX, methotrexate; NA, not applicable; pts, patients; RF, rheumatoid factor; SJC, swollen joint count; SSZ, sulfasalazine; ΔmTSS, variations in modified total Sharp score.