Biological DMARD strategy studies addressing biological DMARD dose reduction or stopping—study outcomes
| Patient group | Biologic | Study (n=total number enrolled) | Outcome | Result |
|---|---|---|---|---|
| DMARD-naive | ADA | Detert 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) | |||
| IFX | van 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 8 | 14/12/8/18 (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 naïve | ADA | Smolen 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) | |||
| ETN | Emery EULAR 2013 (PRIZE)††68 (n=306) | Week 39 after achieving remission | Groups: ETN25+MTX vs MTX vs placebo | |
| Sustained DAS remission | 63.5 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 IR | ETN | Smolen 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 weeks | 82.6 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) | |||
| TCZ | Huizinga 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 IR | CZP | Smolen EULAR 2011/EULAR 2012 (CERTAIN)71 86 (n=194) | Week 52 CDAI remission in patients who achieved CDAI remission at weeks 20 and 24 | Remission retained in 3/17 prior CZP vs 2/6 placebo patients |
| Established RA | ADA & ETN | Fautrel ACR 2012/EULAR 2013 (STRASS)72 87 88 (n=137) | 18 months | Groups: 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) | |||
| ETN | van Vollenhoven ACR 2012/ EULAR 2013 (DOSERA)73 89 (n=91) | Week 48 | Groups: ETN50 vs ETN25 vs placebo | |
| Non-failure** (%) in patients on ETN 50 mg weekly+MTX and LDA or DAS28 remission for ≥11 months | 52 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.