| Drug Therapy Comparison Category | Study, Yr Risk of Bias Ratings | Study Design N Duration | Comparison (Dose) | Results |
|---|---|---|---|---|
| Corticosteroids vs. csDMARDs | CAMERA-II, 201294 Medium | RCT N=239 2 yrs | PRED (10 mg/day) + MTX (10 mg/week) vs. MTX (10 mg/week) | Overall discontinuation: 28% vs. 29.8% at 2 years Discontinuation due to adverse events: 14% vs. 17% Serious adverse events: 2.0% vs. 4.0% Specific adverse events: Nausea: 19.6% vs. 36.1, p=0.006 ALT > ULN: 12.8% vs. 27.7%, p=0.016 AST > ULN: 6.8% vs. 17.6%, p=0.016 Headache: 19.6% vs. 26% No difference in infections |
| Corticosteroids vs. csDMARDs | CARDERA, 200793 Medium | RCT N=467 2 yrs | PNL (60 mg/day tapered over 34 weeks) + MTX (7.5-15 mg/week) vs. MTX | Overall discontinuation: 47% vs. 16.2% at 2 years Discontinuation due to adverse events: 12.2% vs. 6.8% Serious adverse events: 19.0% vs. 21.0% Specific adverse events: Respiratory tract infection: 49.0% vs. 54.0% Nausea/vomiting: 20.0% vs. 15.0% Abdominal pain: 9.0% vs. 7.0% Headache: 10.0% vs. 6.0% Dizziness: 6.0% vs. 4.0% |
| Corticosteroids vs. csDMARDs | Montecucco et al., 20123 Medium | Open label RCT N=220 12 months | PRED (12.5 mg/day for 2 weeks then taper to 6.25 mg/day) + MTX (10-25 mg/week) vs. MTX (10-25 mg/week) | Overall discontinuation: 8.2% vs. 10.9% Discontinuation due to adverse events: 5.5% vs. 9.1%, p=0.29 Serious adverse events: NR Specific adverse events: NR |
| Corticosteroids vs. csDMARDs | CareRA, 2015,95 2015,98 201799 Medium | Open label RCT N=379 2 yrs | High-risk patients: 1: MTX (15 mg/week) + SSZ (2 g/day) + PRED (60 mg/day tapered to 7.5 mg/day) vs. 2: MTX + PRED (30 mg tapered to 5 mg/day) vs. 3: MTX + LEF (10 mg/day) + PRED (30 mg tapered to 5 mg/day) vs. Low-risk patients: 4: MTX 15 mg/week vs. 5: MTX + PRED (30 mg tapered to 5 mg/day) | Overall discontinuation: 8.2%,9.2%, 8.6%, 6.4%,11.6% Discontinuation due to adverse events: NR No significant serious adverse events: 15.3%, 15.3%, 10.8%, 14.9%, 16.3%, p=NR, NS Specific adverse events: Rash: 4.1%, 3.1%,1.1%, 6.4%, 4.7% |
| Corticosteroids vs. csDMARDs | BARFOT #2, 2005,78 2009,97 2014,138,
140
Medium High for 4-yr outcomes | Open label RCT N=259 2 yrs 4-yr followup | PNL 7.5 mg/day + DMARD (SSZ 2 g/day or MTX 10 mg/week) vs. DMARD (SSZ 2 g/day or MTX 10 mg/week) | Overall discontinuation: 11.8% vs. 19.8% Discontinuation due to adverse events: 1.7% vs. 0.0% Serious adverse events: NR Specific adverse events: Rash: 5% vs. 6.9% |
| High-Dose Corticosteroids | Durez et al., 200718 a b | RCT N=44 1 yr | IFX (3 mg/kg at weeks 0, 2, 6 until 46 weeks) + MTX (7.5-20 mg/wk) vs. Methyl-PNL (1 g weeks 0, 2, 6 and every 8 weeks until 46 weeks) + MTX vs. MTX | Overall discontinuation: 6.7% vs. 6.7% vs. 14.3% Discontinuation due to adverse events: 6.7% vs. 0.0% vs. 0.0% Serious adverse events: 0.0% vs. 0.0% vs. 6.7% Specific adverse events: Benign infection: 80.0% vs. 80.0% vs. 93.3% Mild hepatotoxicity: 14.3% vs. 20.0% vs. 33.5% |
| csDMARD Monotherapy Versus csDMARD Monotherapy | BARFOT #1, 200327 High | RCT N=245 2 yrs | PNL (7.5-15 mg/day for 1-3 months) + MTX (5-15 mg/week) vs. SSZ (2-3 g/day) + PNL (up to 10 mg/day) | Overall discontinuation: 19.5% vs. 47.7% Discontinuation due to adverse events: 11.5% vs. 33.3% Serious adverse events: NR Specific adverse events: NR |
| csDMARD Monotherapy Versus csDMARD Monotherapy | NOR-DMARD 201228 High | Obser-vational N=1,102 3 yrs | MTX (10 mg-15 mg/week) vs. SSZ (2 g/day) | Overall discontinuation: 48.1% vs. 78.9% Discontinuation due to adverse events: 15.4% vs. 36% Serious adverse events: NR Specific adverse events: Infections: 34.1% vs. 20.0%, p<0.001 Nausea: 18.9% vs. 13.1%, p<0.07 Abdominal pain: 4.0% vs. 8.0%, p<0.03 Rash: 2.7% vs. 9.1%, p<0.001 |
| csDMARD Monotherapy Versus csDMARD Monotherapy | NOR-DMARD 201228 High | Obser-vational N=1,102 3 yrs | MTX (10 mg-15 mg/week) vs. SSZ (2 g/day) | Overall discontinuation: 48.1% vs. 78.9% Discontinuation due to adverse events: 15.4% vs. 36% Serious adverse events: NR Specific adverse events: Infections: 34.1% vs. 20.0%, p<0.001 Nausea: 18.9% vs. 13.1%, p<0.07 Abdominal pain: 4.0% vs. 8.0%, p<0.03 Rash: 2.7% vs. 9.1%, p<0.001 |
| csDMARD Combination Therapy vs. csDMARD Monotherapy | Dougados et al., 199921,104
a Medium | RCT N=209 1 yr 5-yr followup | SSZ (2-3 g/day) + MTX (7.5 to 15 mg/week) vs. SSZ vs. MTX | Overall discontinuation: 29.2%, 30.9%, 21.7% Discontinuation due to adverse events: 12.5%, 14.7%, 10.1% Serious adverse events: 1.0%, 0.0%, 2.0% Specific adverse events: Nausea: 49.0%, 32.0%, 23.0%, p=0.007 |
| csDMARD Combination Therapy vs. csDMARD Monotherapy | Haagsma 199723
a Medium | RCT N=105 1 yr | SSZ (1-3 g/day) vs. MTX (7.5-15 mg/week) vs. MTX + SSZ | Overall discontinuation: 35.3%, 5.7%, 16.7% Discontinuation due to adverse events: 26.5%, 5.7%, 13.9% Serious adverse events: 8.8%, 0.0%, 0.0% Specific adverse events: Nausea: 29.4%, 25.7%, 63.9% Upper respiratory infection: 17.6%, 20.0%, 27.8% |
| csDMARD Combination Therapy vs. csDMARD Monotherapy | Nijmegen RA Inception 200926 Medium High for 12 months | Obser-vational N=230 1 yr | (SSZ failures) Switch from SSZ to MTX (7.5 mg-30 mg/week) vs. MTX and continue SSZ (750-3,000 mg/day) | Overall discontinuation:33.9% vs. 50.0%, p=0.013 Discontinuation due to adverse events: 18.5%, 11.3% Serious adverse events: NR Specific adverse events: NR |
| csDMARD Combination Therapy vs. csDMARD Monotherapy | COBRA 1997,24 2002100,
141 Medium | RCT N=155 5 yrs | PNL (60 mg tapered over 28 weeks) + MTX (7.5 mg/week stopped after 40 weeks) + SSZ (2,000 mg/day) vs. SSZ | Overall discontinuation: 8.0% vs. 29.1%, p=0.0008 Discontinuation due to adverse events: 2.6% vs. 7.6% Serious adverse events: 2.6% vs. 7.6% Specific adverse events: GI complaints: 14.5% vs. 12.7% |
| csDMARD Combination Therapy vs. csDMARD Monotherapy | COBRA Light, 201425,
105 Medium | RCT N=164 1 yr | PNL (60 mg tapered to 7.5 mg/day) + MTX 7.5 mg/week) + SSZ (2 g/day) vs. PNL (30 mg/d tapered to 7 mg/day + MTX (25 mg/week) ETN intensification in both groups if DAS>1.6 at week 25 or 39 | Overall discontinuation: 3.7% vs. 4.9% Discontinuation due to adverse events: NR Serious adverse events: 11.1% vs. 19.8% Specific adverse events: Leukopenia: 1.0% vs. 4.0% |
| csDMARD Combination Therapy vs. csDMARD Monotherapy | FIN-RACO 1999,22 2010,142 2013,143 2004,101 2004,102 2010145 Medium | RCT N=199 2 yrs 5-yr followup | MTX (7.5-10 mg/week) + HCQ (300 mg/day) + SSZ (2 g/day) + PNL (5-10 mg/day) vs. DMARD (SSZ could be changed to MTX if adverse event or lack of response) | Overall discontinuation: 10.3% vs. 7.1% Discontinuation due to adverse events: 23.7% vs. 22.4% Serious adverse events: 3.1%, 5.1% Specific adverse events: Elevated liver enzymes (AAT and AP > 2x normal): 11.3% vs. 23.5%, p=0.026 |
| csDMARD Combination Therapy vs. csDMARD Monotherapy | tREACH 2013,4 2014,146 2016147 Medium | RCT N=515 1 yr | MTX (25 mg/week) + SSZ (2 g/day) + HCQ (400 mg/day) + GCs intramuscularly vs. MTX + SSZ + HCQ + GC oral taper (15 mg/day tapers off at 10 weeks) vs. MTX + GC oral taper | Overall discontinuation: 15% vs. 9.7% vs. 10.3% Discontinuation due to adverse events: 1.1%, 0.0%, 2.1% Serious adverse events: 5.0%,11.0%, 10.0% Specific adverse events: Headache: 11.0% vs. 14.0% vs. 13.0% |
| TNF Biologic + csDMARD vs. TNF biologic | PREMIER 2006,15 2008,103 2010,149 2010,115 2012,116 2013,117 2014,118 2015119
c Medium | RCT N=799 2 yrs | ADA (40 mg biweekly) + MTX (20 mg/week) vs. ADA vs. MTX | Overall discontinuation: 24.3% vs. 39.1% vs. 34.2%, p<0.001 Discontinuation due to adverse events: 11.9% vs. 9.5% vs. 7.4%, p=0.21 Serious adverse events: 18.5%, 21.1%, 15.9%, p=0.192 Specific adverse events: Higher serious infections (n per 100 pt-years) in ADA + MTX vs. ADA: 2.9, 0.7, p<0.05 |
| Non-TNF Biologic + csDMARD vs. Non-TNF Biologic | AVERT, 20157
a
d Medium | RCT N=351 2 yrs | ABA (125 mg/week) + MTX (7.5-20 mg/week) vs. ABA vs. MTX | Overall discontinuation: 13.4%, 21.6%, 17.2% Discontinuation due to adverse events: 1.7%, 4.3%, 2.6% Serious adverse events: 6.7%, 12.1%, 7.8% Specific adverse events: Serious infection: 0.8% vs. 3.4% vs. 0% |
| Non-TNF Biologic + csDMARD vs. Non-TNF Biologic | FUNCTION 201632
a
d Medium | RCT N=1,162 1 yr | TCZ (4 mg/kg monthly) + MTX (20 mg/week) vs. TCZ (8 mg/kg monthly) + MTX vs. TCZ vs. MTX | Overall discontinuation: 20.3%, 22%, 19.2%, 21.8% Discontinuation due to adverse events: 12.1%, 20.3%, 11.6%, 7.4% Serious adverse events: 10%, 10.7%, 8.6%, 8.5% Specific adverse events: NR |
| Non-TNF Biologic + csDMARD vs. Non-TNF Biologic | U-Act-Early 201633
a
d Medium | RCT N=317 2 yrs | TCZ (8 mg/kg monthly) + MTX (10-30 mg/week) vs. TCZ vs. MTX | Overall discontinuation: 26.4%, 21.4%, 27.8% Discontinuation due to adverse events: 8.5%, 9.7%, 7.4%, p=0.82 Serious adverse events: 16%, 18.4%, 12%, p=0.44 Specific adverse events: NR |
| csDMARDs vs. tsDMARDs | Conaghan 201629 Medium | RCT N=108 1 yr | TOF (20 mg/day) + MTX (10-20 mg/week) vs. TOF vs. MTX | Overall discontinuation: 22.2%, 25%, 43.2% Discontinuation due to adverse events: 11.1%, 5.6%, 13.5% Serious adverse events: 5.6%, 2.8%, 5.4% Specific adverse events: Rash: 2.8%, 11.1%, 0.0% Headache: 8.3%, 5.6%, 5.4% Upper respiratory infection: 8.3%, 5.6%, 5.4% Diarrhea: 2.8%, 5.6%, 2.7% |
| TNF Biologic vs. csDMARD Monotherapy | HIT HARD 201334
a Medium (DAS, ACR) High (SHS) | RCT N=172 48 weeks | ADA (40 mg biweekly x 24 weeks) + MTX (15 mg/week) vs. MTX | Overall discontinuation: 12.6% vs. 32.9% Discontinuation due to adverse events: 4% vs. 7% Serious adverse events: 13.7% vs. 19.5% Specific adverse events: NR |
| TNF Biologic vs. csDMARD Monotherapy | HOPEFUL 1 201435,
150 Medium | RCT 334 52 weeks | ADA (40 mg biweekly) + MTX (6-8 mg/week) vs. MTX | Overall discontinuation: 15.2% vs. 22.1% Discontinuation due to adverse events: 4.1% vs. 2.5% Serious adverse events: 0.6% vs. 0.6% Specific adverse events: Injection site reactions: 10.5% vs. 3.7%, p=0.02 |
| TNF Biologic vs. csDMARD Monotherapy | OPTIMA 2013,37 2014,151 2016152
a Low | RCT N=1,032 78 weeks | ADA (40 mg biweekly) + MTX (7.5-20 mg/week) vs. MTX | Overall discontinuation: 22.3% vs. 24.2% Discontinuation due to adverse events: 8.9% vs. 7.9% Serious adverse events: 7.2% vs. 6.2% Specific adverse events: Bronchitis: 0.0%, 0.9% Dizziness: 1.0%, 0.0% |
| TNF Biologic vs. csDMARD Monotherapy | PREMIER 2006,15 2008,103 2010,149 2010,115 2012,116 2013,117 2014,118 2015119
c Medium | RCT N=799 2 yrs | ADA (40 mg biweekly) + MTX (20 mg/week) vs. ADA vs. MTX | Overall discontinuation: 24.3% vs. 39.1% vs. 34.2%, p<0.001 Discontinuation due to adverse events: 11.9% vs. 9.5% vs. 7.4%, p=0.21 Serious adverse events: 18.5%, 21.1%, 15.9%, p=0.192 Specific adverse events: Higher rates of serious infections (n per 100 pt-years) in ADA + MTX vs. ADA: 2.9, 0.7, p<0.05 |
| TNF Biologic vs. csDMARD Monotherapy | PROWD 200816, 2016152 Medium (16 weeks) High (56 weeks) | RCT N=148 56 weeks | ADA (40 mg biweekly) + MTX (7.5-20 mg/week) vs. MTX | Overall discontinuation: 25.0% vs. 37.0% Discontinuation due to adverse events: 8.0% vs. 11.0% Serious adverse events: 17.3% vs. 15.1% Specific adverse events: Abdominal pain: 1.4% vs. 0.0% Nausea: 21.3% vs. 32.9% Diarrhea: 10.7% vs. 8.2% Headache: 10.7% vs. 6.8% |
| TNF Biologic vs. csDMARD Monotherapy | C-OPERA 201613
a Medium (24 weeks) High (52 weeks, 2 yrs) | RCT N=316 2 yrs | CZP (400 mg biweekly x 4 weeks, then 200 mg biweekly) + MTX (8-12 mg/week) vs. MTX | Overall discontinuation: 53.5% vs. 63.7% Discontinuation due to adverse events: 6.3% vs. 3.8% Serious adverse events: 10.7% vs. 11.5% Specific adverse events: Nausea: 27.0% vs. 24.2% Injection site reaction: 3.1% vs. 1.3% Interstitial Lung disease: 4.4% vs. 0.6% Hepatic disorders: 42.8% vs. 44.6% |
| TNF Biologic vs. csDMARD Monotherapy | C-EARLY 201738,
39 Medium | RCT N=879 52 weeks Aggressive RA | CZP (400 mg biweekly) + MTX (10-25 mg/wk) vs. MTX | Overall discontinuation: 24.2% vs. 34.7% Discontinuation due to adverse events: 7.7 vs. 7.8%, p=NS, NR Serious adverse events: 10.6% vs. 9.2%, p=NS, NR Specific adverse events: Nausea: 12.6% vs. 10.1% Upper respiratory tract infection: 10.9% vs. 5.1% Urinary tract infection: 7.3% vs. 7.4% Headache: 6.8% vs. 3.7% |
| TNF Biologic vs. csDMARD Monotherapy | COMET 200812,
108,
109,
154–156
a Medium | RCT N=542 2 yrs | ETN (50 mg/week) + MTX (7.5 mg/week) vs. MTX | Overall discontinuation: 19.3% vs. 29.5% Discontinuation due to adverse events: 10.2% vs. 12.7% Serious adverse events: 12.0% vs. 12.7% Specific adverse events: Malignancy: 1.5% vs. 1.5% Upper respiratory infection: 45.0% vs. 44.0% Nausea: 53.0% vs. 50.0% Infusion/injection site reactions: 1.0% vs. 2.0% |
| TNF Biologic vs. csDMARD Monotherapy | Enbrel ERA 200014,
110–112
a Medium | RCT N=632 1 yr (1-yr open-label extension) | ETN (25 mg twice weekly) vs. MTX (20 mg/week) | Overall discontinuation: 25.6% vs. 40.5% Discontinuation due to adverse events: 7.3% vs. 12.4% Serious adverse events: 12.0% vs. 12.0% Specific adverse events: Injection site reaction: 39.0% vs. 9.0%, p<0.05 Nausea: 20.0% vs. 31.0%, p<0.05 |
| TNF Biologic vs. csDMARD Monotherapy | Marcora et al., 2006113 Medium | RCT N=26 24 weeks | ETN (25 mg twice weekly) vs. MTX (7.5-15 mg/week) | Overall discontinuation: 0.0% vs. 0.0% Discontinuation due to adverse events: NA Serious adverse events: 0.0% vs. 0.0% Specific adverse events: Injection site reaction: 8.3% vs. 0.0% |
| TNF Biologic vs. csDMARD Monotherapy | ASPIRE 200417,
106,
107
a Medium | RCT N=1,049 54 weeks | IFX (3 mg/kg/8 weeks) + MTX (20 mg/week) vs. IFX (6 mg/kg/8 weeks) + MTX vs. MTX | Overall discontinuation: 21.4%, 23.8%, 25.5% Discontinuation due to adverse events: 9.5%, 9.6%, 3.2% Serious adverse events: 11.0%, 14.0%, 14.0% Specific adverse events: Infusion or injection site reaction: 21.0%, 15.0%, 7.0% TB: 0.8%, 0.3%, 0.0% Serious infection: 5.6%, 5.0%, 2.1%, p=0.02 |
| TNF Biologic vs. csDMARD Monotherapy | Quinn et al., 200541
a Medium | RCT N=20 2 yrs | IFX 3 mg/kg 0, 2, 6, and every 8 weeks) + MTX (7.5-25 mg/wk) vs. MTX (7.5-25 mg/week) | Overall discontinuation: NR Discontinuation due to adverse events: 5.0% overall Serious adverse events: NR Specific adverse events: NR |
| TNF Biologic vs. csDMARD Monotherapy | Durez et al., 200718 a b | RCT N=44 1 yr | IFX (3 mg/kg at weeks 0, 2, 6 until 46 weeks) + MTX (7.5-20 mg/wk) vs. MTX | Overall discontinuation: 6.7% vs. 14.3% Discontinuation due to adverse events: 6.7% vs. 0.0% Specific adverse events: Benign infection: 80.0%% vs. 93.3% Mild hepatotoxicity: 14.3% vs. 33.5% |
| TNF Biologic vs. csDMARD Combination Therapy | IMPROVED, 20139,
120,
158 High | RCT N=161 2 yrs | ADA (40 mg biweekly) + MTX (25 mg/wk) vs. MTX + PRED (7.5 mg/day) + HCQ (400 mg/day) + SSZ (2 g/day) | Overall discontinuation: NR Discontinuation due to adverse events: NR Specific adverse events: Increase liver enzymes: 8.4% vs. 4.0% |
| TNF Biologic vs. csDMARD Combination Therapy | SWEFOT, 201310,
121–126 Medium | RCT, open label N=258 1 yr | IFX (3 mg/kg at 0,2,6 weeks then biweekly) + MTX (20 mg/wk) vs. MTX + SSZ (2 g/day) + HCQ (400 mg/day) | Overall discontinuation: 31.5% vs. 18.0%, p = 0.014 Discontinuation due to adverse events: 10.8% vs. 7.8% Specific adverse events: GI symptoms (not specified): 11.5% vs. 0.7% Skin and allergic reactions: 2.3% vs. 8.5% |
| TNF Biologic vs. csDMARD Combination Therapy | NEO-RACo, 201340,
127,
128 Low | RCT N=99 2 yrs | IFX (3 mg/kg) + FIN-RACo [MTX (25 mg/week) + SSZ 2 g/day) + HCQ (35 mg/kg/week) + PRED (7.5 mg/day)] for 26 weeks vs. FIN-RACo | Overall discontinuation: 8% vs. 8.2% Discontinuation due to adverse events: 2.0% vs. 0.0% Serious adverse events: 6.0% vs. 8.0% Specific adverse events: GI: 56.0% vs. 61.0% Respiratory: 56% vs. 67.0% Elevated liver enzymes: 12.0% vs. 16.0% No significant differences between arms overall |
| Non-TNF Biologic vs. csDMARD Monotherapy | AGREE, 200931,
129–131
a Low | RCT N=509 2 yrs | ABA (10 mg/kg) + MTX (7.5 mg/week) vs. MTX | Overall discontinuation: 9.4% vs. 10.3% Discontinuation due to adverse events: 3.1% vs. 4.3% Serious adverse events: 7.8% vs. 7.9% Specific adverse events: Upper respiratory infection: 10.2% vs. 10.3% Low |
| Non-TNF Biologic vs. csDMARD Monotherapy | AVERT, 20157
a
d Medium | RCT N=351 2 yrs | ABA (125 mg/week) + MTX (7.5-20 mg/week) vs. ABA vs. MTX | Overall discontinuation: 13.4%, 21.6%, 17.2% Discontinuation due to adverse events: 1.7%, 4.3%, 2.6% Serious adverse events: 6.7%, 12.1%, 7.8% Specific adverse events: Serious infection: 0.8% vs. 3.4% vs. 0% |
| Non-TNF Biologic vs. csDMARD Monotherapy | FUNCTION 201632
a
d Medium | RCT N=1,162 1 yr | TCZ (4 mg/kg monthly) + MTX (20 mg/week) vs. TCZ (8 mg/kg monthly) + MTX vs. TCZ vs. MTX | Overall discontinuation: 20.3%, 22%, 19.2%, 21.8% Discontinuation due to adverse events: 12.1%, 20.3%, 11.6%, 7.4% Serious adverse events: 10%, 10.7%, 8.6%, 8.5% Specific adverse events: NR |
| Non-TNF Biologic vs. csDMARD Monotherapy | IMAGE, 201230,
132,
133 Low | RCT N=755 2 yrs | RIT (1 g days 1 and 15) + MTX (7.5-30 mg/week) vs. RIT (500 mg days 1 and 15) + MTX vs. MTX | Overall discontinuation: 15%, 15%, 29% Discontinuation due to adverse events: 2.8%, 3.2%, 6.8% Serious adverse events: 13.2%, 14.9%, 16.9% Specific adverse events: Infusion-related reaction: 18.4% vs. 14.1% vs. 12.4% |
| Non-TNF Biologic vs. csDMARD Monotherapy | U-Act-Early 201633
a
d Medium | RCT N=317 2 yrs | TCZ (8 mg/kg monthly) + MTX (10-30 mg/week) vs. TCZ vs. MTX | Overall discontinuation: 26.4%, 21.4%, 27.8% Discontinuation due to adverse events: 8.5%, 9.7%, 7.4%, p=0.82 Serious adverse events: 16%, 18.4%, 12%, p=0.44 Specific adverse events: NR |
| TNF vs. Non-TNF | ORBIT, 20168 High | RCT N=329 1 yr | RIT (1 g on days 1 and 15 and after 26 if persistent disease activity) vs. ADA (40 mg biweekly) or ETN (50 mg/week) | Overall discontinuation: 18.8% vs. 17.7% Discontinuation due to adverse events: 1.4% vs. 1.3% Serious adverse events:25.7% vs. 17.2% Specific adverse events: Infections: 53.5% vs. 70.9% Injection site reactions less with RIT p=0.003 |
| Combination and Therapy Strategies | BeSt, 200579–91 Low Medium for 10-yr outcomes | RCT N=508 12 months plus 10-yr followup | DAS-driven treatment; 1: sequential monotherapy starting with MTX (15 mg/week) vs. 2: stepped-up combination therapy: MTX, then SSZ, then HCQ, then PRED vs. 3: combination with tapered high-dose PRED (60 mg/d to 7.5 mg/day) vs. 4: combination MTX (25-30 mg/week) with IFX (3 mg/kg every 8 weeks, per DAS, could be titrated to 10 mg/kg) | 5 yrs Overall discontinuation: 12.0%, 22.0%, 15.0%, 9.0%; 2 vs. 4, p=0.05 Discontinuation due to adverse events: NR Serious adverse events: 33.0%, 28.0%, 28.0%, 31.0%, p=0.76 Specific adverse events: NR 10 yrs No significant differences in serious adverse events (SAE per 100 pt yrs) 13.2, 10.9, 12.1, 13.4, p=0.47 |
| Combination and Therapy Strategies | TEAR, 201220,
159 High | RCT N=755 2 yrs | 1: immediate MTX plus ETN vs. 2: immediate MTX plus SSZ plus HCQ vs. 3: step-up MTX to MTX + ETN vs. 4: step-up MTX to MTX + SSZ + HCQ | Overall discontinuation: 42.4%, 34.8%, 39.5%. 34.9% Discontinuation due to adverse events: 1&2: 1.9%, 3&4: 1.3% Serious adverse events: 13.6%, 14.3%, 12.9%, 12.5%, p=0.94 Specific adverse events: NR |
| Combination and Therapy Strategies | GUEPARD 200992 Medium for 12-week outcomes High for 52-week outcomes | RCT N=65 1 yr | 1: ADA 40 mg every 2 weeks plus MTX; treatment adjusted every 3 months to achieve DAS28 <3.2 2: MTX (max 20 mg/wk) | Overall discontinuation: 15.2% vs. 9.4% Discontinuation due to adverse events: NR Serious adverse events: 15.2% vs. 15.6% Specific adverse events: NR |
| Combination and Therapy Strategies | OPERA 2017160–163 Medium | RCT N=180 2 yrs | ADA (40 mg biweekly) + MTX (7.5-20 mg/week) vs. MTX | Overall discontinuation: 10.1% vs. 16.5% Discontinuation due to adverse events: 2.2% vs. 1.1% Serious adverse events: 4% vs. 11% Specific adverse events: Bronchitis: 1.1% vs. 1.1% Leukopenia: 0% vs. 1.1% |
| Combination and Therapy Strategies | Bili et al., 201411 High | Observational N=2,101 10 yrs | 1: TNFa inhibitors alone or in combination with MTX 2: MTX alone or in combination with other nonbiologic DMARDs 3: Non-MTX, nonbiologic DMARDs | Overall discontinuation: NR Discontinuation due to adverse events: NR Serious adverse events: NR Specific adverse events: Incident coronary artery disease (adjusted hazard ratio): 0.45 (CI, 0.21 to 0.96) vs. 0.54. (CI, 0.27 to 1.09) vs. reference group |
| Combination and Therapy Strategies | ERAN Inception Cohort, 2013137 High | Observational N=766 2 yrs | 1: Initial SSZ 2: Initial MTX 3: MTX + SSZ+ HCQ | Overall discontinuation: NR Discontinuation due to adverse events: NR Serious adverse events: NR Changed DMARD due to adverse drug reaction: 59% vs. 23% vs. 2% |
Included in network meta-analysis (NWMA)
This study evaluates comparisons in both the High-Dose Corticosteroid and TNF Biologic vs. csDMARD monotherapy categories.
This study evaluates comparisons in both the csDMARD vs. TNF Biologic and TNF Biologic vs. csDMARD monotherapy categories.
These studies evaluate comparisons in both the csDMARD vs. Non-TNF Biologic and Non-TNF Biologic vs. csDMARD monotherapy categories.
AAT = alanine aminotransferase; ABA = abatacept; ACR = American College of Rheumatology; ADA = adalimumab; ALT = alanine transaminase; AP = alkaline phosphatase; AST = aspartate aminotransferase; csDMARD = conventional synthetic disease-modifying antirheumatic drug CZP = certolizumab pegol; DAS = Disease Activity Score (based on 44 joints); DMARD = disease modifying antirheumatic drug; ETN = etanercept; g = grams; GC = glucocorticoid; GI = gastrointestinal; HCQ = hydroxychloroquine; IFX = infliximab; kg = kilograms; LEF = leflunomide; methyl-PNL = methylprednisolone; mg = milligram; mg/d = milligrams per day; MTX = methotrexate; N = number; NR = not reported; PNL = prednisolone; PRED = prednisone; pt-years = patient-years; RCT = randomized controlled trial; RIT = rituximab; SHS = Sharp/van der Heijde Score; SSZ = sulfasalazine; TB = tuberculosis; TCZ = tocilizumab; TNF = tumor necrosis factor; TOF = tofacitinib; ULN = upper limit of normal; vs. = versus; wk = week.
From: Results
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