| Drug Therapy Comparison Category | Study, Yr Risk of Bias Rating | Study Design N Duration | Comparison (Dose) | Results (Patient-Reported Outcomes, Functioning, Quality of Life) |
|---|---|---|---|---|
| Corticosteroids vs. csDMARDs | CAMERA-II, 201294 Medium | RCT N=239 2 yrs | PRED (10mg/day) + MTX (10mg/wk) vs. MTX (10mg/wk) | Higher mean HAQ score in MTX vs. MTX + PRED at 2 yrs (0.7 vs. 0.5), Mean difference (95% CI): −0.18 (−0.34 to −0.02) (p=0.027). Similar statistically significant differences were found at 3, 6, 12, and 18 months. |
| Corticosteroids vs. csDMARDs | CARDERA, 200793 Medium | RCT N=467 2 yrs | PNL (60 mg/day tapered over 34 wks) + MTX (7.5-15 mg/wk) vs. MTX | At 2 yrs, no difference in HAQ mean change in MTX + PNL vs. MTX (−0.28 vs. −0.29, p=NR) Mean increase in SF-36 PCS was 5.8. No difference in the SF-36 PCS mean change between MTX and MTX + PNL (p=NR). No difference in SF-36 MCS or EQ-5D between groups. |
| Corticosteroids vs. csDMARDs | Montecucco et al., 20123 | 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) | More improvement in patient-reported pain (VAS, mean change) in the PRED + MTX group than in the MTX group at 4 and 12 months, but not 6 or 9 months |
| Corticosteroids vs. csDMARDs | CareRA, 2015,95,
98 201799 Medium | RCT N=379 2 yrs | High-risk patients: 1: MTX (15 mg/wk) + 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/wk vs. 5: MTX + PRED (30 mg tapered to 5 mg/day) | No differences in functional capacity among the groups at 16 weeks and 54 weeks as measured by clinically meaningful change in HAQ change (p= NS). Fewer patients had a HAQ score of 0 in the MTX-TSU group (23.4%) than in the COBRA Slim group (51.2%) (p=0.006). |
| Corticosteroids vs. csDMARDs | BARFOT #2, 2005,78 2009,97 2014,138,
140 Medium (1, 2, 10 yr outcomes) High (4 yr outcomes) | RCT N=259 2 yrs 4-yr followup | PNL 7.5 mg/day + DMARD (SSZ 2 g/day or MTX 10 mg/wk) vs. DMARD (SSZ 2 g/day or MTX 10 mg/wk) | Significant improvement in physical function as measured by mean decrease in HAQ from baseline between the PNL + csDMARD group compared with the csDMARD group at all time points including 3, 6, 12, 18 months and 2 yrs (p=0.003). Significant difference between groups still present at 4 yrs (p=0.034). Patients in remission at 2 yrs had significantly lower HAQ scores at both 2 and 4 yrs. |
| High-dose corticosteroids | Durez et al., 200718
b Medium | RCT N=44 1 yr | IFX 3 mg/kg 0,2,6 and every 8 wks + MTX (7.5-20 mg/wk) vs. MTX + Methyl-PNL (1 g at 0,2,6 and every 8 wks) vs. MTX | At 52 weeks, significantly greater HAQ improvements over time in IFX + MTX and methyl-PNL + MTX groups than in the MTX group (p=0.001) |
| High-dose corticosteroids | IDEA, 201496 Medium | RCT N=112 26 weeks 50-week open label | IFX (3 mg/kg at wks 0, 2, 6, 14, 22) + MTX (10 to 20 mg/wk) vs. Methyl-PNL (250 mg single dose) + MTX | At 26 and 78 weeks, no difference in functional capacity (HAQ-DI mean change: IFX + MTX, −0.85 vs. methyl-PNL + MTX: −0.79, p=0.826) |
| csDMARD Monotherapy vs. 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/wk) vs. SSZ (2-3g/day) + PNL (up to 10 mg/day) | At 2 yrs, no difference in function between groups (HAQ mean change from baseline: −0.35 vs. −0.38, p=0.752) |
| csDMARD Monotherapy vs. csDMARD Monotherapy | NOR-DMARD, 201228 High | Observational N=1,102 3 yrs | SSZ (2 g/day) vs. MTX (10mg-15 mg/wk) | At 6 months, significant difference in function between SSZ group and MTX group (mean modified HAQ [0-3] change from baseline: −0.13 vs. −0.26, p=0.002). This difference was not significant after adjusting for propensity score quintile and physician global VAS (p=0.13). At 6 months, no difference in quality of life as measured by mean SF-36 PCS change from baseline, MCS change from baseline. At 6 months, no significant difference in patient-reported pain (VAS, mean change from baseline) or patient-reported fatigue (VAS, mean change from baseline) in MTX group vs. SSZ group. |
| csDMARD Combination Therapy vs. csDMARD Monotherapy | Dougados et al., 199921 Maillefert et al., 2003104 Medium | RCT N=209 1 yr (5-yr followup) | SSZ (2-3g/day) + MTX (7.5 to 15 mg/wk) vs. SSZ vs. MTX | At 1 yr, no difference in HAQ change from baseline: −0.32 (95% CI, −0.53 to −0.10) vs. −0.46 (95% CI, −0.68 to −0.25) vs. −0.51 (95% CI, −0.76 to −0.26) or 5 yrs (mean HAQ 0.6 vs. 0.6, p=0.9). |
| csDMARD Combination Therapy vs. csDMARD Monotherapy | Haagsma et al., 199723 Medium | RCT N=105 1 yr | SSZ (1-3 g/day) + MTX (7.5-15 mg/wk) vs. MTX vs. SSZ | At 52 weeks, no differences in function between groups (HAQ change from baseline: SSZ, −0.32 (95% CI, −0.53 to −0.10) vs. MTX, −0.46 (95% CI, −0.68 to −0.25) vs. SSZ + MTX, −0.51 (95% CI, −0.76 to −0.26) |
| csDMARD Combination Therapy vs. csDMARD Monotherapy | COBRA, 1997,24 2002,100 2009141 Medium High for 11-yr radio-graphic outcomes | RCT N=155 5 yrs | PNL (60 mg tapered over 28 wks) + MTX (7.5 mg/wk stopped after 40 wks) + SSZ (2 g/day) vs. SSZ | At 28 weeks, more improvement in function (HAQ, mean change) and in patient-reported pain (VAS, mean change) in the PNL + MTX + SSZ group than in the SSZ group At 56 weeks and 5 yrs, no difference in mean change in function or pain |
| csDMARD Combination Therapy vs. csDMARD Monotherapy | COBRA-Light, 201425,
105 Medium | RCT N=164 1 yr | PNL (60 mg tapered over 28 wks) + MTX (7.5 mg/wk) + SSZ (2,000 mg/day) (“COBRA”) vs. PNL (30 mg tapered over 28 wks), MTX (7.5 mg to 25 mg/wk) “COBRA Light”) At 26 wks, each group could get ETN 50 mg subcutaneous wkly if no DAS <1.6 | At 26 weeks and at 52 weeks, no difference in functional capacity between groups (respectively: HAQ, mean change from baseline: −0.8 vs. −0.8, p=0.49; HAQ, mean scores: 0.57 vs. 0.61, p=0.35) |
| csDMARD Combination Therapy vs. csDMARD Monotherapy | FIN-RACo, 1999,22 2004,101,
102 2010,142,
145 2013143 Medium | RCT N=199 2 yrs | MTX (7.5-10 mg/wk) + 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) | At 2 yrs, no significant difference in improvement of physical function between groups (HAQ, mean change −0.6 vs. −0.6) At 2 yrs, significantly less work disability in the combination group than the monotherapy group (median work disability days per patient-observation yr, 12.4 vs. 32.2, p=0.008) |
| csDMARD Combination Therapy vs. csDMARD Monotherapy | tREACH, 2013,4 2014,146 2016147,
148 Medium | RCT N=515 1 yr | MTX (25 mg/wk) + SSZ (2 g/day) + HCQ (400 mg/day) + glucocorticoid IM vs. MTX + SSZ + HCQ + glucocorticoid oral taper (15 mg/day tapers off at 10 wks) vs. MTX + glucocorticoid oral taper | At 3, 6, and 9 months and 1 yr, no significant difference in function between groups (mean HAQ or mean change in HAQ from baseline) At 3, 6, and 9 months and 1 yr, no significant difference in EQ-5D between groups |
| csDMARD + TNF Biologic vs. TNF Biologic | PREMIER, 2006,15 2008,103 2010,115,
149 2012,116 2013,117 2014,118 2015119
c Medium | RCT N=799 2 yrs | ADA (40 mg biwkly) + MTX (20 mg/wk) vs. ADA vs. MTX | At 3 months and 6 months, no significant differences in function or HRQOL between groups At 1 yr, HAQ-DI mean change was greater in the ADA + MTX group than in both the ADA group (p=0.0002) and the MTX group (p=0.0003) At 76 weeks, no significant difference in SF-36 scales or pain At 2 yrs: Function improved significantly more in the ADA + MTX group than in the MTX group (HAQ-DI mean change: -1 vs. −0.9, p<0.05; HAQ-DI response, p=NS). Significantly more patients in the ADA + MTX group had a HAQ-DI score of 0 than in either monotherapy group (33% vs. 19% vs. 19%, p<0.001) SF-36 PCS improved more in ADA + MTX group than in MTX group (p<0.0001); no difference in MCS SF36 MCS improved more in the ADA group than the MTX group (p=0.015). Patient-reported pain (VAS, mean) was lower in the ADA + MTX group than the ADA group (p<0.0001). No difference between the ADA and MTX groups. More days of employment and fewer missed work days in the ADA + MTX group than in the MTX group |
| csDMARD + Non-TNF Biologic vs. csDMARD | AVERT, 20157
d Medium | RCT N=351 2 yrs | ABA (125 mg/wk) + MTX (7.5-15 mg/wk) vs. ABA vs. MTX | At 12 and 18 months: nonsignificant but higher percentages of patients in the ABA + MTX group than in the ABA group and the MTX group with HAQ-DI response (respectively by time points, 65.5% vs. 52.6% vs. 44%; 21.8% vs. 16.4% vs. 10.3%) |
| csDMARD + Non-TNF Biologic vs. csDMARD | FUNCTION, 201632
d Medium | RCT N=1,162 2 yrsa | TCZ (4 mg/kg monthly) + MTX (20 mg/wk) vs. TCZ (8 mg/kg monthly) + MTX vs. TCZ vs. MTX | At 52 weeks, significantly greater improvement in mean HAD-DI scores from baseline in TCZ 8 mg + MTX group than in MTX group (p=0.0024) At 24 weeks and at 52 weeks: Significantly greater change in SF-36 PCS scores in the TCZ 8 mg/kg + MTX group than in the MTX group (p=0.0014 and p=0.0066 for both time points) No differences in SF-36 PCS scores between the TCZ 4 mg/kg + MTX group and the MTX group or between TCZ and MTX group No differences in SF-36 MCS scores |
| csDMARD + Non-TNF Biologic vs. csDMARD | U-Act-Early, 201633
d Medium | RCT N=317 2 yrs | TCZ (8 mg/kg IV monthly) + MTX 10-30 mg/wk) vs. TCZ vs. MTX | At 24 weeks, physical function differed significantly (HAQ Dutch) between TCZ + MTX group and each monotherapy group (p=0.0275) At 52 weeks and 2 yrs, physical function did not differ significantly (from baseline measures) between groups Significantly greater improvement in mean SF-36 PCS over time in TCZ + MTX group and TCZ monotherapy group vs. MTX monotherapy group (p=0.044 and p=0.012, respectively). No differences in SF-36 MCS over time between groups. Significantly greater improvement in mean EQ-5D scores over time in TCZ + MTX group vs. MTX monotherapy group (p=0.018). No significant difference between TCZ and MTX monotherapy groups. |
| csDMARDs vs. tsDMARDs | Conaghan et al., 201629 Medium | RCT N=108 1 yr | TOF (20 mg/d) + MTX (10-20 mg/wk) vs. TOF vs. MTX | At 3, 6, and 12 months, no significant differences in improvement in function (HAQ-DI) between the TOF + MTX group and either the MTX or the TOF groups |
| TNF Biologic vs. csDMARDMono therapy | HIT HARD, 201334 Medium High for SHS | RCT N=172 48 weeks | ADA (40 mg biwkly for 24 wks) + MTX (15 mg/wk) vs. MTX | At 24 weeks: Significantly greater physical function in ADA+MTX group than in MTX group (HAQ-DI mean 0.49 vs. 0.72, p=0.0014) Significantly greater SF-36 PCS (44.0 vs. 39.8, p=0.0002) No difference in SF-36 MCS at 24 weeks At 48 weeks: no difference between groups in function or quality of life measures |
| TNF Biologic vs. csDMARD Monotherapy | HOPEFUL 1, 201435,
150 Medium | RCT N=334 1 yr | ADA (40 mg biwkly) + MTX (6-8 mg/wk) vs. MTX | At 26 weeks, significantly greater improvement from baseline in physical function in ADA + MTX group than in MTX group (decrease from baseline in mean HAQ-DI score: 0.6±0.6 vs. 0.4±0.6, p<0.001) At 26 weeks, significantly more patients in ADA + MTX group than in MTX group achieved normal functionality (HAQ-DI score <0.5: 60.0% vs. 36.8%, p=0.001) |
| TNF Biologic vs. csDMARD Monotherapy | OPTIMA, 2013,32 2014,151 2016152 Low | RCT N=1,032 78 weeks | ADA (40 mg biwkly) + MTX (7.5-20 mg/wk) vs. MTX | At week 26: Significantly greater functional improvements in ADA + MTX group than in MTX group (HAQ-DI mean score: 0.7 vs. 0.9, p<0.001) Significantly greater proportion of ADA + MTX patients than MTX patients had normal function (40.0% vs. 28.0%, respectively, p<0.001) |
| TNF Biologic vs. csDMARD Monotherapy | PREMIER, 2006,15 2008,103 2010,115,
149 2012,116 2013,117 2014,118 2015119
c Medium | RCT N=799 2 yrs | ADA (40 mg biwkly) + MTX (20 mg/wk) vs. ADA vs. MTX | At 3 months and 6 months, no significant differences in function or HRQOL between groups At 1 yr, HAQ-DI mean change was greater in the ADA + MTX group than in both the ADA group (p=0.0002) and the MTX group (p=0.0003) At 76 weeks, no significant difference in SF-36 scales or pain At 2 yrs: Function improved significantly more in the ADA + MTX group than in the MTX group (HAQ-DI mean change: -1 vs. −0.9, p<0.05; HAQ-DI response, p=NS). Significantly more patients in the ADA + MTX group had a HAQ-DI score of 0 than in either monotherapy group (33% vs. 19% vs. 19%, p<0.001) SF-36 PCS improved more in ADA + MTX group than in MTX group (p<0.0001); no difference in MCS SF36 MCS improved more in the ADA group than the MTX group (p=0.015). More days of employment and fewer missed work days in the ADA + MTX group than in the MTX group |
| TNF Biologic vs. csDMARD Monotherapy | PROWD, 2008,16,
152 2016151 Medium (16-week outcomes) High (56-week outcomes) | RCT N=148 54 weeks | ADA 40 mg subcutaneous every 2 wks + MTX (7.5-25 mg/wk) vs. MTX (7.5-25 mg/wk) | At 16 weeks, fewer patients in the ADA + MTX group than in the MTX had job loss, although difference was statistically NS (12 [16%] vs. 20 [27.3%], p=0.092). At 56 weeks, job loss was significantly lower with ADA + MTX (−18.6%) than MTX (−39.7%, p<0.005) At 56 weeks, function from baseline improved significantly in the ADA + MTX group compared with the MTX group (change in HAQ from baseline: −0.7 vs. −0.4, p=0.005) |
| TNF Biologic vs. csDMARD Monotherapy | C-OPERA, 2016,13 2017153 Medium (24-week outcomes) High (52 week outcomes) | RCT N=316 2 yrs | CZP (400 mg biwkly × 4 wks, then 200 mg biwkly) + MTX (8-12 mg/wk) vs. MTX | At 52 weeks, significantly greater improvement in HAQ-DI in the CZP + MTX group than in the MTX group At 2 yrs, no significant difference in HAQ remission between groups (73.0% vs. 63.7%, p=0.09) |
| TNF Biologic vs. csDMARD Monotherapy | C-EARLY, 201738,
39 Medium High (WPS-RA work productivity outcomes) | RCT N=879 1 yr | CZP (400 mg biwkly X 4 wks, then 200 mg biwkly) + MTX (10-25 mg/wk) vs. MTX | At 52 weeks, significantly greater improvement in function in the CZP + MTX group than in the MTX group (HAQ-DI mean change from baseline −1.00 vs. −0.82, p<0.001) Significantly more patients in the CZP+MTX group than in the MTX group achieved normal function (HAQ-DI <0.5: 48.1% vs. 35.7%, p=0.002) More improvement in fatigue (by BRAF-MDQ) and work productivity (by WPS-RA) in the CZP + MTX group across all questions At all weeks preceding (12, 20, 24, 36, and 40), similar greater improvements in CZP + MTX were seen |
| TNF Biologic vs. csDMARD Monotherapy | COMET, 2008,12 2009,154 2010,108,
109 2012,155 2014156 Medium | RCT N=542 2 yrs | ETN (50 mg/wk) + MTX (7.5 mg/wk) vs. MTX | At 52 weeks: Significantly greater improvement in function in the ETN + MTX group than in the MTX group (HAQ, mean change: −1.02 vs. −0.72, p<0.0001) Significantly more patients in the ETN + MTX group than in the. MTX group achieved normal function (HAQ-DK0.5: 55% vs. 39%, p=0.0004) Significantly higher SF-36 PCS scores in the ETN + MTX group than in the MTX group (13.7 vs.10.7, p=0.003) Improvement in following work-related outcomes favoring the ETN + MTX group: Fewer patients had to stop working: 8.6% vs. 24% (p=0.004) Less absenteeism: 14.2 vs. 31.9 missed workdays |
| TNF Biologic vs. csDMARD Monotherapy | Enbrel ERA, 2000,14 2003,110 2005,112 2006111 Medium | RCT N=632 1 yr 1-yropen-label extension | ETN (25 mg twice wkly) vs. MTX (20 mg/wk) | At 12 months, no difference in function between groups (mean HAQ) In the open-label extension until 24 months, significantly more patients in the ETN group than in the MTX group achieved improvement in function (HAQ improvement >0.5 units: 37% vs. 55%, p<0.001) |
| TNF Biologic vs. csDMARD Monotherapy | Marcora et al., 2006113 Medium | RCT N=26 6 months | ETN (25 mg twice wkly) vs. MTX (7.5-20 mg/wk) | At baseline, HAQ mean was 1.9 vs. 1.2 for ETN and MTX groups, respectively At 12 weeks, HAQ mean was 1.2 vs. 0.6 for ETN and MTX groups, respectively At 24 weeks, HAQ mean was 1.0 vs. 0.6 for ETN vs. MTX groups, respectively |
| TNF Biologic vs. csDMARD Monotherapy | ASPIRE, 2004,17 2006,107 2009,106 2017157 Medium | RCT N=1,049 54 weeks | IFX (3 mg/kg/8 wks) + MTX (20 mg/wk) vs. IFX (6 mg/kg/8 wks) + MTX vs. MTX | At 54 weeks: significantly greater improvements in HAQ scores from baseline in both the IFX (3 mg/kg) + MTX and IFX (6 mg/kg) + MTX groups than in the MTX group (% with HAQ increase >0.22 units from baseline: 76%, 75.5%, 65.2%, p<0.004) From 30-54 weeks: significantly greater HAQ improvements in both IFX (3 mg/kg) + MTX and IFX (6 mg/kg) + MTX groups than in the MTX group (mean decrease in HAQ scores from baseline: 0.88, 0.80, vs. 0.68, p≤0.001) At 54 weeks: Significantly higher SF-36 PCS in both the IFX + MTX groups than in the MTX group (11.7,13.2, vs. 10.1, p=0.003) Significant improvements in IFX (either 3 mg/kg or 6 mg/kg) + MTX group than in the MTX group in employability (OR, 2.4, p<0.001) Fewer patients were unemployable in the IFX (either 3 mg/kg or 6 mg/kg) + MTX group than in the MTX group (8% vs. 14%, p=0.05) No differences between groups in employment rate (0.5% vs. 1.3%, p>0.05) |
| TNF Biologic vs. csDMARD Monotherapy | Quinn et al., 200541 Medium | RCT N=20 2 yrs | IFX 3 mg/kg 0, 2, 6 and every 8 wks) + MTX (7.5-25 mg/wk) vs. MTX (7.5-25 mg/wk) | At 54 weeks, significant functional benefit (by HAQ) favoring IFX + MTX over MTX (p=0.05) |
| TNF Biologic vs. csDMARD Monotherapy | Durez et al., 200718
b Medium | RCT N=44 1 yr | IFX 3 mg/kg 0,2,6 and every 8 wks + MTX (7.5-20 mg/wk) vs. MTX + Methyl-PNL (1 g at 0,2,6 and every 8 wks) vs. MTX | At 52 weeks, significantly greater HAQ improvements overtime in IFX + MTX and methyl-PNL + MTX groups than in the MTX group (p=0.001) |
| TNF Biologic vs. csDMARD Combination Therapy | IMPROVED, 2013,9 2014,158 2016120 High | RCT N=161 2 yrs | ADA (40 mg biwkly) + MTX (25 mg/wk) vs. MTX + PRED (7.5 mg/day) + HCQ (400 mg/day) + SSZ (2 g/day) | At 4, 8, 12, and 24 months: Mean HAQ scores did not differ between groups (respectively by time points: 0.86 vs. 0.88, p=0.77; 0.74 vs. 0.81, p=0.51; 0.87 vs. 0.81, p=0.6; 0.90 vs. 0.83) SF-36 PCS and MCS did not differ by group at any time point. At 12 months, lower patient-reported pain (VAS, mean) in the ADA +MTX group. |
| TNF Biologic vs. csDMARD Combination Therapy | SWEFOT, 2009,10 2012,122 2013,121,
123,
126 2015,125 2016124 Medium | RCT N=258 1 yr | IFX (3 mg/kg at 0, 2, 6 wks then biwkly) + MTX (20 mg/wk) vs. MTX + SSZ (2 g/day) + HCQ (400 mg/day) | At 12 months, EQ-5D dimensions did not differ significantly between groups |
| TNF Biologic vs. csDMARD Combination Therapy | NEO-RACO, 2013,40 2014,128 2015127 Low | RCT N=99 2 yrs | IFX (3 mg/kg) +MTX (25 mg/wk) + SSZ (2 g/day) + HCQ (35 mg/kg/wk) + PRED (7.5 mg/day) for 26 wks vs. FIN-RACo | At 2 and 5 yrs, mean HAQ scores did not differ significantly between groups |
| Non-TNF Biologic vs. csDMARD Monotherapy | AGREE, 2009,31 2011,129,
130 2015131 Low (ACR response, DAS28 remission, DAS, radio-graphic outcomes, adverse events) Medium (HAQ-DI, SF-36) | RCT N=509 2 yrs | ABA (10 mg/kg) + MTX (7.5 mg/wk) vs. MTX | At 1 yr, significantly greater functional benefit in the ABA + MTX group than in the MTX group (HAQ-DI % change of >0.3 units from baseline: 71.9% vs. 62.1%, p=0.024) At 1 yr, significantly greater improvement in SF-36 scales in the ABA + MTX group than in the MTX group: SF-36 MCS (8.15 vs. 6.34, p=0.046) and SF-36 PCS (11.68 vs. 9.18, p=0.005) |
| Non-TNF Biologic vs. csDMARD Monotherapy | AVERT, 20157
d Medium | RCT N=351 2 yrs | ABA (125 mg/wk) + MTX (7.5-15 mg/wk) vs. ABA vs. MTX | At 12 and 18 months: nonsignificant but higher percentages of patients in the ABA + MTX group than in the ABA group and the MTX group with HAQ-DI response (respectively by time points, 65.5% vs. 52.6% vs. 44%; 21.8% vs. 16.4% vs. 10.3%) |
| Non-TNF Biologic vs. csDMARD Monotherapy | FUNCTION, 201632
d Medium | RCT N=1,162 2 yrsa | TCZ (4 mg/kg monthly) + MTX (20 mg/wk) vs. TCZ (8 mg/kg monthly) + MTX vs. TCZ vs. MTX | At 52 weeks, significantly greater improvement in mean HAD-DI scores from baseline in TCZ 8 mg + MTX group than in MTX group (p=0.0024) At 24 weeks and at 52 weeks: Significantly greater change in SF-36 PCS scores in the TCZ 8 mg/kg + MTX group than in the MTX group (p=0.0014 and p=0.0066 for both time points) No differences in SF-36 PCS scores between the TCZ 4 mg/kg + MTX group and the MTX group or between TCZ and MTX group No differences in SF-36 MCS scores |
| Non-TNF Biologic vs. csDMARD Monotherapy | IMAGE, 2011,30,
133 2012132 Low | RCT N=755 2 yrs | RIT (1 g days 1 and 15) + MTX (7.5-30 mg/wk) vs. RIT (500 mg days 1 and 15) + MTX vs. MTX | At week 52: Significantly greater improvement in physical function (measured by HAQ-DI decrease >0.22) in the RIT 1 g days 1 and 15 + MTX and the RIT 500 mg days 1 and 15 + MTX groups than in the MTX group (HAQ response: 88% and 87% vs. 77%, p<0.05). This difference remained for the RIT 1 g + MTX vs. the MTX group at 2 yrs (p<0.05). Significantly greater improvement in the SF-36 PCS for both the RIT + MTX groups than in the MTX group (mean changes: 10.76 and 10.07 vs. 7.24, p=<0.0001) Nonsignificantly greater changes in SF-36 MCS scores for both the RIT + MTX groups than in the MTX group (mean changes: 6.66 and 6.18 vs. 4.84) Significantly greater improvement in patient-reported pain (VAS, mean change) and in patient-reported fatigue (FACIT-F) in the RIT +MTX groups than in the MTX group. |
| Non-TNF Biologic vs. csDMARD Monotherapy | U-Act-Early, 201633
d Medium | RCT N=317 2 yrs | TCZ (8 mg/kg IV monthly) + MTX 10-30 mg/wk) vs. TCZ vs. MTX | At 24 weeks, physical function differed significantly (HAQ Dutch) between TCZ + MTX group and each monotherapy group (p=0.0275) At 52 weeks and 2 yrs, physical function did not differ significantly (from baseline measures) between groups Significantly greater improvement in mean SF-36 PCS over time in TCZ + MTX group and TCZ monotherapy group vs. MTX monotherapy group (p=0.044 and p=0.012, respectively). No differences in SF-36 MCS over time between groups. Significantly greater improvement in mean EQ-5D scores over time in TCZ + MTX group vs. MTX monotherapy group (p=0.018). No significant difference between TCZ and MTX monotherapy groups. |
| TNF vs. Non-TNF | ORBIT, 20168 High | RCT N=329 1 yr | RIT (1g days 1 and 15 and after day 26 if persistent disease activity) vs. ADA (40 mg biwkly) or ETN 50 mg/wk) | At 6 and 12 months: Function improved more in the RIT group than in the ADA or ETN groups (HAQ mean change from baseline) at 6 months (6 months, −0.44 vs. −0.31, p=0.0391; 12 months, −0.49 vs. −0.38, p=0.0391) The EQ-5D, Hospital Anxiety and Depression Scale anxiety and depression outcomes did not differ by group |
| Combination and Therapy Strategies | BeSt, 2005,79 2007,85 2008,84 2009,83,
86 2010,81 2011,89,
90 2012,80,
91 2013,82 2014,88 201687 Low Medium (10-yr outcomes) | RCT N=508 12 months (10 yrs) | DAS-driven treatment; G1: sequential mono-therapy starting with MTX (15 mg/week) vs. G2: stepped-up combination therapy (MTX, then SSZ, then HCQ, then PRED) vs. G3: combination with tapered high-dose PRED (60 mg/d to 7.5 mg/day) vs. G4: combination (MTX 25-30 mg/week) with IFX (3 mg/kg every 8 weeks, per DAS, could be titrated to 10 mg/kg) | At 3, 6, 9, and 12 months, significantly greater improvement in functional capacity in G1 and G2 vs. G3 and G4 (HAQ score improvement from baseline, p=0.05, p<0.05, p<0.05, and p<0.05 at each time point, respectively) At 3 and 6 months, significantly greater improvement in SF-36 PCS in G1 and G2 than in G3 and G4 (p<0.001); no difference in SF-36 MCS At 2 yrs, no significant differences among groups in functional capacity At 5- and 10-yrfollowup: no significant differences between groups |
| Combination and Therapy Strategies | TEAR, 2012,20 2013159 High | RCT N=755 2 yrs | Immediate MTX (20 mg/wk) plus ETN (50 mg/wk) vs. Immediate MTX plus SSZ (1-2 g/day) plus HCQ (400 mg/day) vs. Step up MTX to combo (MTX plus ETN) vs. Step up MTX to combo (MTX plus SSZ plus HCQ) | At 48 and 102 weeks, no difference in functional capacity among groups |
| Combination and Therapy Strategies | GUEPARD, 200992 Medium (12-wk outcomes) High (52-wk outcomes) | RCT N=65 1 yr | 1: ADA 40 mg every 2 wks + MTX (max 20 mg/wk); treatment adjusted every 3 months to achieve DAS28 <3.2 2: MTX | At 1 yr, no difference between groups in functional capacity, SF-36 PCS or MCS scores, pain, fatigue, or patient global assessment |
| Combination and Therapy Strategies | OPERA, 2013160 2014,36 2015,161 2016,162 2017163 Medium | RCT N=180 2 yrs | ADA (40 mg biwkly) + MTX (7.5-20 mg/wk) vs. MTX (also used intra-articular triamcinolone therapy in both groups) | At 1 yr, significantly greater improvement in functionality in ADA + MTX group than in MTX group (HAQ median change: −0.88 vs. −0.63, p=0.012) At 1 yr: Significantly greater improvement in SF-12 PCS median change in ADA + MTX group than in MTX group (13.2 vs. 10.6, p=0.015) Significantly greater improvement in pain in ADA + MTX group than in MTX group (VAS median: 7 vs. 20, p=0.007) No differences between groups in changes in SF-12 MCS or EQ-5D At 2 yrs, no differences between groups in physical function, quality of life, pain, or fatigue |
Although the FUNCTION trial lasted a total of 2 yrs, the latest time point at which KQ 2-eligible outcomes were reported was 1 yr.
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.
ABA = abatacept; ACR = American College of Rheumatology; ADA = adalimumab; BRAF-MDQ = Bristol Rheumatoid Arthritis Fatigue - Multidimensional Questionnaire; CI = confidence interval; csDMARD = conventional synthetic DMARD; CZP = certolizumab pegol; DAS = Disease Activity Score (based on 44 joints); DAS28 = Disease Activity Score 28; DMARD = disease-modifying antirheumatic drug; EQ-5D = EuroQoL standardized instrument; ETN = etanercept; g = gram; G = group; HAQ = Health Assessment Questionnaire; HAQ-DI = Health Assessment Questionnaire-Disability Index; HCQ = hydroxychloroquine; HRQOL = health related quality of life; 1FX = infliximab; IM = intramuscular; kg = kilogram; max = maximum; LEF = leflunomide; mg = milligrams; MCS = mental component score; methyl-PNL = methylprednisolone; MTX = methotrexate; N = number (of patients); NR = not reported; NS = not significant; OR = odds ratio; PCS = physical component score; PNL = prednisolone; PRED = prednisone; RCT = randomized controlled trial; RIT = rituximab; SF-12 = 12-Item Short Form Survey; SF-36 MCS = Short Form 36 Health Survey Mental Component Score; SF-36 PCS = Short Form 36 Health Survey Physical Component Score; SHS = Sharp/van der Heijde Score; SSZ = sulfasalazine; TCZ = tocilizumab; TNF = tumor necrosis factor; TOF = tofacitinib; TSU = tight step-up; VAS = visual analogue scale; vs. = versus; wk(s) = week(s); WPS-RA = Work Productivity Survey - Rheumatoid Arthritis; yr(s) = year(s).
From: Results
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