Table 4

Biological DMARD strategy studies addressing biological DMARD dose reduction or stopping—study outcomes

Patient groupBiologicStudy (n=total number enrolled)OutcomeResult
DMARD-naiveADADetert 2013 (HIT HARD)21 (n=172)Primary EP:Groups: ADA+MTX/ MTX vs Placebo MTX/MTX*
Week 48 DAS28 (mean (SD))3.2 (1.4) vs 3.4 (1.6) (p=0.49)
Other:
ACR responses (%)ACR 50: 52.6 vs 51.4 (p=0.88), ACR 70: 40.5 vs 34.0 (p=0.40)
DAS28 remission (%)42.4 vs 36.8 (p=0.47)
Horslev–Petersen EULAR 2013 (OPERA)53 (n=180)Year 2:Groups: ADA+MTX/ MTX vs placebo+MTX/MTX†
DAS28CRP (median (95% CI))2.0 (1.7 to 4.4) vs 2.0 (1.7 to 4.5) (p=0.97)
Remission (DAS28CRP<2.6)66% vs 69% (p=0.79)
IFXvan der Kooij 200966/Klarenbeek 2011)84/Dirven 2011 (BeSt)64 (n=508)


van der Kooij 2009 (BeSt)63 (n=508)
Groups: 1 to 4‡
DFR (%) year 4; year 814/12/8/18 (p=0.14); 18/19/17/15 (p=0.9)
4 year joint damage progression>SDC (%) 51/54/38/31 (p<0.05 for group 4 vs groups 1 and 3 and for group 3 vs group 2)
Groups: Initial vs delayed IFX:
Discontinuation of IFX due to sustained DAS44 ≤2.4 2 years after IFX initiation (%)56 vs 29 (OR(95% CI) 2.56 (1.27 to 5.16) p=0.008))
van den Broek 2011 (BeSt)85 (n=508)Groups: Initial vs delayed IFX
Discontinuation of IFX due to sustained DAS ≤ 2.4 (for 6 months) (n)77/120 vs 27/109
Sustained DAS remission after IFX cessation (n(%))43/77 (56) vs11/27 (41)
DFR (n(%))15 (27) vs 0 after at least 1 year of follow-up
Predictor of restarting IFX (for DAS>2.4)HR (95% CI) 1.8 (0.9 to 3.7)
Nam 2013 (IDEA)54 (n=112)Week 78: stopped IFX due to sustained remission (n(%))§14/55 (25) of the IFX group
MTX naïveADASmolen EULAR 2012 (OPTIMA)78 (n=1032)Groups: ADA_continue vs ADA withdrawal
Maintenance of DAS28<3.2 from week 52 to 78 in patient who achieved LDA at with ADA+MTX at weeks 22 and 26 (%)87 vs 65 (p=0.002)
Emery EULAR 2011 (OPTIMA)79 (n=1032)Week 78 outcomes in patient who achieved LDA with ADA+MTX at weeks 22 and 26:Groups: ADA_continue vs ADA_withdrawal
ACR20/50/70 (%)95/89/77 vs 94/80/65 (p=0.72/ 0.11/ 0.05)
DAS28 <3.2(%)81 vs 91 (p=0.04)
DA28 <2.6(%)66 vs 86 (p=0.001)
ΔmTSS≤0.5(%)89 vs 81 (0.06)
ETNEmery EULAR 2013 (PRIZE)††68 (n=306)Week 39 after achieving remissionGroups: ETN25+MTX vs MTX vs placebo
Sustained DAS remission63.5 vs 38.5 vs 23.1 (ETN25+MTX vs MTX p=0.0051; ETN25+MTX vs placebo p<0.0001, MTX vs placebo 0.0595)
ΔmTSS≤0.5(%)87.9 vs 96.4 vs 89.8 (ETN25+MTX vs MTX 0.1124; ETN25+MTX vs placebo 0.7609; MTX vs placebo 0.1929)
MTX IRETNSmolen 2013 (PRESERVE)71 (n=834)Primary EP:Groups: ETN50+MTX vsETN25+MTX vs placebo+MTX
Week 88 LDAS28 (%) in patients who achieved sustained LDA with ETN 50 mg weekly+MTX for 36 weeks82.6 vs 79.1 vs 42.6
ETN50+MTX vs PBO+MTX (mean difference (95% CI) 40.8 (32.5 to 49.1, p<0.0001)
ETN25+MTX vs PBO+MTX (mean difference (95% CI) 35.9 (27.0 to 44.8), p<0.0001)
TCZHuizinga EULAR 201370 (ACT-RAY) (n=556)Week 104:Groups: TCZ add-on vs switch
TCZ discontinuation after achieving the protocol-defined sustained remission (%)57 vs 47 (p=0.13)
Flare (%)85 vs 87 (p=0.075)
Study DFR (%)5.1 vs 1.8 (0.037)
Mixed DMARD IRCZPSmolen EULAR 2011/EULAR 2012 (CERTAIN)71 86 (n=194)Week 52 CDAI remission in patients who achieved CDAI remission at weeks 20 and 24Remission retained in 3/17 prior CZP vs 2/6 placebo patients
Established RAADA & ETNFautrel ACR 2012/EULAR 2013 (STRASS)72 87 88 (n=137)18 monthsGroups: S (spacing ADA & ETN injections) vs M (maintain full dose ADA & ETN)¶
Taper an and stopping TNFi (n (%))S-arm: 47 (73.4) tapered TNFi, of whom 24 (37.5) stopped
Relapse occurred at least once (%)81vs. 56, p=0.0009
Structural damage progression (n (%))In 4 (6.7) and 3 (4.5) patients (p=0.3)
ETNvan Vollenhoven ACR 2012/ EULAR 2013 (DOSERA)73 89 (n=91)Week 48Groups: ETN50 vs ETN25 vs placebo
Non-failure** (%) in patients on ETN 50 mg weekly+MTX and LDA or DAS28 remission for ≥11 months52 vs 44 vs 13
ETN50 vs placebo :OR 7.2 (1.7–29.8 (p=0.007) ETN50
ETN 25 vs placebo: OR 4.2 (1.0–17.0 (p=0.44) vs PBO, ETN25 vs ETN50 NS
  • *HIT HARD comparator groups: ADA+MTX vs placebo+MTX for 24 weeks. After 24 weeks, both groups treatment with MTX only.

  • †OPERA comparator groups: ADA+MTX vs placebo+MTX for 1 year. After 1 year, both groups treatment with MTX only.

  • ‡BeSt comparator groups: Group 1 sequential monotherapy; Group 2 step-up combination therapy; Group 3 initial combination with prednisone; Group 4 initial combination with IFX.

  • §Sustained remission=DAS<1.6 for 6 months.

  • ¶STRASS comparator groups: Patients in stable DAS28 remission (DAS28≤2.6 for ≥6 months) on ETN or ADA for ≥ 1 year with no structural damage progression on X-rays since last X-ray assessment, patients randomised to one of 2 arms: S (spacing ADA & ETN injections) vs M (maintain ADA & ETN as full regimen).

  • **Failure=DAS28 ≥3.2 and an increase of SDAS28 ≥0.6 or disease progression as determined by the investigator or patient.

  • ††Sustained DAS remission=DAS28<2.6 at weeks 76 and 91, no corticosteroid boost between weeks 52–64.

  • ADA, adalimumab; csDMARD, conventional synthetic disease modifying antirheumatic drug; CZP, certolizumab pegol; DFR, drug free remission; ETN, etanercept; IFX, infliximab; LDA, low disease activity; mTSS, van der Heijde modified sharp scores; MTX, methotrexate; NS, non-significant; SDC, smallest detectable change; TCZ, tocilizumab.