Table 5

Primary outcomes of studies investigating csDMARD, bDMARD and tsDMARD tapering and stopping

Study	Primary outcome	Endpoint (week)	Treatment arm	N	Result	P value
csDMARD tapering
Kaeley 2016 (MUSICA)107	Mean DAS28-CRP	24	ADA 40 mg Q2W+7.5 mg MTX	154	4.12	0.014
Kaeley 2016 (MUSICA)107	Mean DAS28-CRP	24	ADA 40 mg Q2W+20 mg MTX	155	3.75	0.014
Keystone 2016 (CAMEO)144	ΔDAS28-ESR	24	ETN 50 mg QW; MTX discontinuation	98	0.5	0.815
Keystone 2016 (CAMEO)144	ΔDAS28-ESR	24	ETN 50 mg QW +MTX continuation	107	0.04	0.815
Pope EULAR 2017/ACR 2018/2019108–110	ΔDAS28-ESR	76	CZP +csDMARD continuation	37	−2.1	NR
Pope EULAR 2017/ACR 2018/2019108–110	ΔDAS28-ESR	76	CZP +csDMARD discontinuation	44	−2.1	NR
Burmester ACR 2018 (SEMIRA)111	ΔDAS28-ESR	24	TCZ ±csDMARDs; GC tapering	131	0.538	<0.001
Burmester ACR 2018 (SEMIRA)111	ΔDAS28-ESR	24	TCZ ±csDMARDs; GC continuation	128	−0.075	<0.001
Pablos 2018 (JUST-ACT)112	ΔDAS28-ESR week 16 week 28	28	TCZ 8 mg/kg+MTX	82	0.007	95% CI −0.40 to 0.27
Pablos 2018 (JUST-ACT)112	ΔDAS28-ESR week 16 week 28	28	TCZ 8 mg/kg+PLC	82	0.073	95% CI −0.40 to 0.27
Kremer 2018 (COMP-ACT)113	ΔDAS28-ESR week 24 week 40	40	TCZ 162 mg s.c. +PLC	147	0.46	95% CI 0.045 to 0.592
Kremer 2018 (COMP-ACT)113	ΔDAS28-ESR week 24 week 40	40	TCZ 162 mg s.c. +MTX	147	0.14	95% CI 0.045 to 0.592
Edwards 2018 (ACT-TAPER)114	Pat. Maintaining EULAR good/moderate response from week 24–60	60	TCZ 8 mg/kg Q4W+PBO	136	77%	0.036
Edwards 2018 (ACT-TAPER)114		60	TCZ 8 mg/kg Q4W+MTX	136	65%	0.036
Stouten 2018 (CareRA)115 116	DAS28-CRP <2.6	65	MTX +LEF->MTX 15 mg/week	32	94%	0.031
Stouten 2018 (CareRA)115 116	DAS28-CRP <2.6	65	MTX+LEF->LEF 20 mg/day	26	73%	0.031
bDMARD tapering
Oba 2017/Tanaka ACR 2018 (RRRR)140 141	1-year sustained discontinuation rate of INF	106	INF 3 mg/8 mg/10 mg/kg Q8W based on TNF levels	170	24%	0.631
Oba 2017/Tanaka ACR 2018 (RRRR)140 141	1-year sustained discontinuation rate of INF	106	INF standard 3 mg/kg Q8W	167	21%	0.631
Chatzidionysiou 2016 (ADMIRE)142	DAS28 <2.6 at week 28	28	ADA +MTX continuation	16	94%	0.001
Chatzidionysiou 2016 (ADMIRE)142	DAS28 <2.6 at week 28	28	ADA discontinuation; MTX monotherapy	16	33%	0.001
Ghiti Moghadam 2016/2018 (POET)117 118	% of pat. DAS28 ≥3.2 + ΔDAS28 >0.6 for 1 year	52	Stopping TNFi	531	51%	<0.001
Ghiti Moghadam 2016/2018 (POET)117 118	% of pat. DAS28 ≥3.2 + ΔDAS28 >0.6 for 1 year	52	Continuation of TNFi	286	18%	<0.001
Atsumi 2017 (C-OPERA)119	ΔmTSS	104	CZP +MTX continuation	108	0.66	0.001
Atsumi 2017 (C-OPERA)119	ΔmTSS	104	Stopping CZP; MTX+PLC	71	3.01	0.001
Kaneko 2018 (SURPRISE)121	TCZ free rate	104	stopping TCZ; MTX monotherapy	49	67%	0.001
Kaneko 2018 (SURPRISE)121	TCZ free rate	104	stopping TCZ; No DMARD	53	29%	0.001
Weinblatt 2017 (C-EARLY)120	DAS28-ESR ≤3.2 without flares during week 52–104	104	CZP 200 mg Q2W+MTX (standard)	84	49%	Reference
			CZP 200 mg Q4W+MTX (reduced frequency)	126	53%	0.112
			Placebo +MTX (CZP stopped)	79	39%	0.041
Ibrahim 2017 (OPTIRRA)122	Flare rate (ΔDAS28 ≥0.6 + DAS28 >3.2 + ΔSJC OR ΔDAS28 >1.2 + DAS28 >3.2)	24	TNFi 33% tapering; csDMARD	26	12%	0.873
			TNFi 66% tapering; csDMARD	21	29%	0.097
			Control; csDMARD continuation	50	16%	Reference
Bouman 2017 (DRESS)145	Incidence of major flare (ΔDAS28-CRP >1.2 or ΔDAS28-CRP >0.6+DAS28-CRP ≥3.2 for >12 weeks)	144	TNFi dose reduction extension	115	17%	3%, 95% CI -10% to 15%
Bouman 2017 (DRESS)145		144	Usual care extension	57	14%	3%, 95% CI -10% to 15%
l’Ami 2018124	∆DAS28-ESR	28	ADA 40 mg Q3W±MTX	27	−0.14	0.01
l’Ami 2018124	∆DAS28-ESR	28	ADA 40 mg Q2W±MTX	27	0.3	0.01
tsDMARD tapering
Takeuchi 2019 (RA-BEYOND)125	CDAI ≤10	12	Continued BARI 4 mg±csDMARD	281	93%	<0.001
Takeuchi 2019 (RA-BEYOND)125	CDAI ≤10	12	BARI Step-down 2 mg±csDMARD	278	83%	<0.001

Δ, change from baseline; ACR, American College of Rheumatology; ADA, adalimumab; BARI, baricitinib; bDMARD, biological disease-modifying antirheumatic drug; CDAI, Clinical Disease Activity Index; CRP, C-reactive protein; csDMARDs, conventional synthetic disease-modifying antirheumatic drugs; CZP, certolizumab pegol; DAS28, Disease Activity Score of 28 joints; ESR, erythrocyte sedimentation rate; ETN, etanercept; EULAR, European League against Rheumatism; GC, glucocorticoid; INF, infliximab; LEF, leflunomide; mTSS, modified total Sharp Score; MTX, methotrexate; MTX, methotrexate; PLC, placebo; SJC, swollen joint count; TCZ, tocilizumab; TNFi, tumour necrosis factor inhibitor; tsDMARD, targeted synthetic DMARD.