Table 5

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

StudyPrimary outcomeEndpoint (week)Treatment armNResultP value
csDMARD tapering
Kaeley 2016 (MUSICA)107 Mean DAS28-CRP24ADA 40 mg Q2W+7.5 mg MTX1544.120.014
ADA 40 mg Q2W+20 mg MTX1553.75
Keystone 2016 (CAMEO)144 ΔDAS28-ESR24ETN 50 mg QW; MTX discontinuation980.50.815
ETN 50 mg QW +MTX continuation1070.04
Pope EULAR 2017/ACR 2018/2019108–110 ΔDAS28-ESR76CZP +csDMARD continuation37−2.1NR
CZP +csDMARD discontinuation44−2.1
Burmester ACR 2018 (SEMIRA)111 ΔDAS28-ESR24TCZ ±csDMARDs; GC tapering1310.538<0.001
TCZ ±csDMARDs; GC continuation128−0.075
Pablos 2018 (JUST-ACT)112 ΔDAS28-ESR week 16 week 2828TCZ 8 mg/kg+MTX820.00795% CI −0.40 to 0.27
TCZ 8 mg/kg+PLC820.073
Kremer 2018 (COMP-ACT)113 ΔDAS28-ESR week 24 week 4040TCZ 162 mg s.c. +PLC1470.4695% CI 0.045 to 0.592
TCZ 162 mg s.c. +MTX1470.14
Edwards 2018 (ACT-TAPER)114 Pat. Maintaining EULAR good/moderate response from week 24–6060TCZ 8 mg/kg Q4W+PBO13677%0.036
TCZ 8 mg/kg Q4W+MTX13665%
Stouten 2018 (CareRA)115 116 DAS28-CRP <2.665MTX +LEF->MTX 15 mg/week3294%0.031
MTX+LEF->LEF 20 mg/day2673%
bDMARD tapering
Oba 2017/Tanaka ACR 2018 (RRRR)140 141 1-year sustained discontinuation rate of INF106INF 3 mg/8 mg/10 mg/kg Q8W based on TNF levels17024%0.631
INF standard 3 mg/kg Q8W16721%
Chatzidionysiou 2016 (ADMIRE)142 DAS28 <2.6 at week 2828ADA +MTX continuation1694%0.001
ADA discontinuation; MTX monotherapy1633%
Ghiti Moghadam 2016/2018 (POET)117 118 % of pat. DAS28 ≥3.2 + ΔDAS28 >0.6 for 1 year52Stopping TNFi53151%<0.001
Continuation of TNFi28618%
Atsumi 2017 (C-OPERA)119 ΔmTSS104CZP +MTX continuation1080.660.001
Stopping CZP; MTX+PLC713.01
Kaneko 2018 (SURPRISE)121 TCZ free rate104stopping TCZ; MTX monotherapy4967%0.001
stopping TCZ; No DMARD5329%
Weinblatt 2017 (C-EARLY)120 DAS28-ESR ≤3.2 without flares during week 52–104104CZP 200 mg Q2W+MTX (standard)8449%Reference
CZP 200 mg Q4W+MTX (reduced frequency)12653%0.112
Placebo +MTX (CZP stopped)7939%0.041
Ibrahim 2017 (OPTIRRA)122 Flare rate (ΔDAS28 ≥0.6 + DAS28 >3.2 + ΔSJC OR ΔDAS28 >1.2 + DAS28 >3.2)24TNFi 33% tapering; csDMARD2612%0.873
TNFi 66% tapering; csDMARD2129%0.097
Control; csDMARD continuation5016%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)144TNFi dose reduction extension11517%3%, 95% CI -10% to 15%
Usual care extension5714%
l’Ami 2018124 ∆DAS28-ESR28ADA 40 mg Q3W±MTX27−0.140.01
ADA 40 mg Q2W±MTX270.3
tsDMARD tapering
Takeuchi 2019 (RA-BEYOND)125 CDAI ≤1012Continued BARI 4 mg±csDMARD28193%<0.001
BARI Step-down 2 mg±csDMARD27883%
  • 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.