Introduction
Materials and methods
Systematic review
Data collection
Network meta-analyses
Base-case and sensitivity analyses
Results
Systematic review
Study design and patient characteristics
Trial (reference) | Compared interventions | Trial design; Patient population | Inclusion criteria | Endpoints | Study period |
---|---|---|---|---|---|
Exclusion criteria
| |||||
Abatacept studies
| |||||
PBO + MTX; ABA 10 mg/kg every four weeks + MTX | Phase 3 RCT; Active RA despite MTX | Met ACR criteria, > = 18 years, RA for > = 1 year, > = 10 SJC, > = 12 TJC, CRP > = 10.0 mg/L, MTX (≥ 15 mg/week) for ≥ 3 months with stable dose for 28 days prior to enrolment | ACR20 at six months; HAQ-DI (≥ 0.3); CFB in joint erosion score at one year | Nov '02 to Oct' 04; 52 weeks | |
Positive tuberculin skin test | |||||
PBO + MTX; ABA 2 mg/kg every four weeks + MTX; ABA 10 mg/kg every four weeks + MTX | Phase 3 RCT; Active RA despite MTX. | Met ACR criteria, > = 10 SJC, > = 12 TJC, CRP > 1 mg/dl, MTX (10 to 30 mg/week) for > = 6 months with stable dose for 28 days prior to enrolment | ACR20 at six months | Date n/s; 52 weeks + 6 months | |
n/s | |||||
ATTEST trial [15] | PBO + MTX; ABA 10 mg/kg every four weeks + MTX; INF 3 mg/kg every eight weeks + MTX | RCT, double-dummy, PBO and active (INF)-controlled; RA and MTX-IR | Met ACR criteria, > = 18 years, RA for > = 1 year, > 10 SJC, > 12 TJC, CRP > 1 mg/dl, MTX > 15 mg/week for > 3 months prior to randomisation, other DMARDs washed out | Reduction in DAS28 with abatacept vs placebo at six months | Feb '05 to June '06; 52 weeks PBO arm = PBO for six months followed by ABA |
Prior experience with abatacept or an other approved biologic RA therapy, failed on > 4 conventional DMARDs | |||||
Adalimumab studies
| |||||
ARMADA [25] | PBO + MTX; ADA 20 mg every other week + MTX; ADA 40 mg every other week + MTX; ADA 80 mg every other week + MTX | RCT; Active RA despite MTX | Met ACR criteria; > = 18 years, > 9 TJC, > 6 SJC, MTX for > = 6 months and stable weekly dose for > = 4 weeks before enrolment, failed treatment with > = 1 DMARD besides MTX, but not > 4 DMARDs | ACR20 | Date n/s; 24 weeks |
Prior anti-CD4 therapy or TNF-α antagonists, history of active listeriosis or mycobacterial infection, any major infection | |||||
DE019 [24] | PBO + MTX; ADA 20 mg weekly + MTX; ADA 40 mg every other week + MTX | RCT; Active RA treated with MTX. | Met ACR criteria; > = 18 years, > = 9 TJC, > = 6 SJC, CRP > 1 mg/dl, either rheumatoid factor positivity or > = 1 joint erosion on radiographs of hands + feet, MTX for > = 3 months at stable dose of 12.5 to 25 mg/week for > = 4 weeks | ACR20 at week 24 | Date n/s; 52 weeks |
Prior anti-CD4 therapy or TNF antagonists; history of: other active inflammatory arthritide, active listeriosis/mycobacterial infection, lymphoma/leukemia within five years; any major infection | |||||
Certolizumab Pegol studies
| |||||
PBO + MTX; CZP 200 mg every other week + MTX; CZP 400 mg every other week + MTX | Phase 3 RCT; Active RA with MTX-IR | > = 18 years, active RA for > = 6 months + < 15 years, > = 9 TJC + SJC with either ESR > = 30 m/hour or CRP > 15 mg/l, MTX for > = 6 months with a stable dosage of > = 10 mg/week for > = 2 months. | ACR20 at week 24; mean CFB in modified total Sharp score at week 52 | Feb '05 to Oct' 06; 52 weeks. ACR20 non-responders at weeks 12 + 14 were withdrawn | |
History of: tuberculosis, malignancy; PPD positive skin test; biologic therapy within 6 months, prior failure to respond to anti-TNF agent | |||||
PBO + MTX; CZP 200 mg every other week + MTX; CZP 400 mg every other week + MTX | Phase 3 RCT; Active RA despite > = 6 months of MTX | Met ACR criteria, > 18 years, RA > 6 months duration but < 15 years, MTX for > 6 months (stable dose > 10 mg/week for > 2 months at baseline) | ACR20 at week 24 | June '05 to Sept' 06; 24 weeks ACR20 non-responders at weeks 12 + 14 were withdrawn | |
Biologic agent in previous six months, severe reaction to biologic agents, no response to previous anti-TNF therapy, history of tuberculosis, PPD positive skin test | |||||
Etanercept studies
| |||||
Weinblatt et al. 1999 [32] | PBO + MTX; ETN 25 mg 2x week + MTX | Double-blind, randomised; Active RA despite > = 6 months of MTX | Met ACR criteria, > = 18 years, > = 6 SJC + TJC, MTX for > = 6 months at stable dose of 15 to 25 mg/week for last 4 weeks, discontinued sulfasalazine + hydroxychloroquine > = 2 weeks + DMARDs other than MTX > = 4 weeks prior to study | ACR 20 at 24 weeks | Date n/s; 24 weeks |
n/s | |||||
PBO + MTX; ETN 25 mg 2x week; ETN 25 mg 2x week + MTX | Randomised, double-blind, parallel group study; RA patients with DMARD-IR | Met ACR criteria, > = 18 years, active disease for 6 months-20 years, > 10 SJC, > 12 painful joints, IR to > = 1 DMARD other than MTX, previous MTX (without toxic effects/lack of response), no MTX within 6 months of enrolment | ACR response (ACR-N) AUC for the first 24 weeks | Oct '00 to July' 01; 52 weeks | |
Prior therapy with ETN or other TNF antagonists, immunosuppressive drugs within 6 months; investigational drug or biologic agent within 3 months, any other DMARDs or corticosteroid within 4 weeks, presence of relevant co morbidity | |||||
Golimumab studies
| |||||
PBO + MTX; GOL 100 mg every four weeks; GOL 50 mg every four weeks + MTX; GOL 100 mg every four weeks + MTX | Phase 3 RCT; active RA despite MTX | Met ACR criteria, > 18 years, RA > = 3 months, tolerated stable MTX dose of 15-25 mg/week for > = 3 months prior to screening, > = 4 SJC & TJC, met the tuberculosis screening criteria | ACR20 at week 14 and improvement from baseline in HAQ-DI score at week 24. | Dec '05 to Sept' 07; 52 weeks. At week 16, patients < 20% CFB in TJC and SJC had medication adjusted | |
Hypersensitivity to GOL, previous anti-TNF agent, RTX, natalizumab, cytotoxic agents, anakinra, DMARDs other than MTX, corticosteroids within four weeks, alefacept or efalizumab within three months. | |||||
Infliximab studies
| |||||
PBO + MTX; INF 3 mg/kg every eight weeks + MTX; INF 3 mg/kg every four weeks + MTX; INF 10 mg/kg every eight weeks + MTX; INF 10 mg/kg every four weeks + MTX | International Phase 3 RCT; Active RA despite MTX | Met ACR criteria, > = 6 SJC + TJC, MTX for > = 3 months not stopped for > 2 weeks, MTX at stable dose > 12.5 mg/week for > = 4 weeks, oral corticosteroids or NSAIDs on stable dose for > = 4 weeks | ACR20 at week 30 | Date n/s; 54 weeks | |
DMARD (not MTX) or non-oral corticosteroids in four weeks before screening, alkylating agents, any other agent to reduce TNF, allergic to murine proteins, serious infections in previous three months, chronic infectious disease | |||||
Rituximab studies
| |||||
PBO + MTX; RTX 500 mg x2 injections + MTX; RTX 1,000 mg x2 injections + MTX | Phase 2b international RCT, double-dummy; Active RA with DMARD-IR and MTX-IR. | Met ACR criteria, 19 to 79 years, RA > 6 months, MTX at 10 to 25 mg/week for > = 12 weeks before randomization, stable dose for last 4 weeks, > 8 SJC + TJC, either ECR > = 28 mm/hour or CRP > = 1.5 mg/dl, IR to 1 to 5 DMARDs (other than MTX) and/or biologic agents discontinued > = 4 weeks before randomization and INF, ADA, leflunomide > = 8 weeks before randomization | ACR20 for RF-positive patients at week 24 | Date n/s; 24 weeks | |
Significant systemic involvement secondary to RA, other illnesses or laboratory abnormalities, severe allergic or anaphylactic reactions to monoclonal antibodies, previous treatment with RTX or any lymphocyte-depleting therapies, recurrent significant infection | |||||
N/S | |||||
Strand et al. 2006 [41] | PBO + MTX; RTX 1,000 mg x2 injections; RTX 1,000 mg x2 injections + cyclophosphamide; RTX 1,000 mg x2 injections + MTX | RCT; Active RA despite MTX | Met ACR criteria, > 21 years, MTX > = 10 mg/week, > = 8 SJC + TJC, CRP > = 15 mg/l and/or ESR > = 28 mm/h, and/or morning stiffness > 45 minutes, plasma rheumatoid factor level > 20 IU/ml | ACR 50 at week 24 | Date n/s; 48 weeks |
Other autoimmune disease, ARA functional class IV disease, active rheumatoid vasculitis, history of systemic diseases associated with arthritis, chronic fatigue syndrome, serious and uncontrolled coexisting diseases | |||||
PBO + MTX; RTX 500 mg x2 injections + MTX; RTX 1,000 mg x2 injections + MTX | Phase 3 RCT; Active RA with MTX-IR and naïve to prior biologic therapy | ≥ 8 SJC + TJC, elevated CRP (≥ 0.6 mg/dL) and/or ESR (≥ 28 mm/h) despite MTX for ≥ 12 wks | ACR20 at week 24 | Date n/s; 48 weeks | |
N/S | |||||
Tocilizumab studies
| |||||
PBO + MTX; TCZ 4 mg/kg every four weeks + MTX; TCZ 8 mg/kg every four weeks + MTX | Phase 3 RCT, parallel group; RA with MTX-IR | Met ACR criteria, adults, RA > 6 months, MTX-IR, > = 6 SJC, > = 8 TJC, CRP > 10 mg/L or ESR > = 28 mm/h, MTX for > = 12 weeks before start of study (stable dose of 10 to 25 mg/week for > = 8 weeks), discontinuation of other DMARDs: leflunomide > = 12 weeks, anakinra > = 1 week, etanercept > = 2 weeks, infliximab or adalimumab > = 8 weeks prior to start of study | ACR20 at 24 weeks | Date n/s; 24 weeks. At week 16, patients < 20% CFB in TJC and SJC were eligible for rescue therapy with TCZ 8 mg/kg | |
other autoimmune diseases, significant systemic involvement secondary to RA, functional class IV RA, inflammatory joint disease other than RA, recurrent infections, active liver disease, anti-TNF agent failure | |||||
Not stated | |||||
LITHE [42] | PBO + MTX; TCZ 4 mg/kg every four weeks + MTX; TCZ 8 mg/kg every four weeks + MTX | Phase 3 RCT, double-blind; RA with MTX-IR | N/S | CFB in Genant-modified Sharp score and AUC in the HAQ-DI at Week 52 | two years A switch to blinded rescue treatment was available at weeks 16 and 28, if required. |
Trial (reference) | Treatment arm | RF status (% positive) | Gender (% F) | Mean age (years) | Mean years since diagnosis | Mean n of prior DMARDs | % pts on NSAIDs | % pts on corticoid steriods | Mean TJC | Mean SJC | Mean pts pain1 (100-mm VAS) | Mean pts GA 2 (100-mm VAS) | Mean phs GA3 (100-mm VAS) | Mean HAQ-DI | Mean CRP (mg/l) | Mean ESR (mm/h) |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Abatacept studies
| ||||||||||||||||
PBO + MTX; ABA 10 mg/kg every four weeks + MTX | 81.8 | 77.8 | 51.5 | 8.5 | 1.3 | 85.5 | 72.1 | 31.0 | 21.4 | 63.3 | 62.7 | 68.0 | 1.70 | 33 | nr | |
78.5 | 81.7 | 50.4 | 8.9 | 1.2 | 82.6 | 68.5 | 32.3 | 22.1 | 65.9 | 62.8 | 67.4 | 1.70 | 28 | |||
PBO + MTX | 90.0 | 66.0 | 54.7 | 8.9 | 21% | nr | 67.2 | 29.2 | 21.8 | 65.2 | 62.8 | 63.3 | 1.00 | 32 | nr | |
ABA 2 mg/kg every four weeks + MTX | 90.0 | 63.0 | 54.4 | 9.7 | 18.1% | 67.6 | 28.2 | 20.2 | 64.5 | 59.4 | 61.0 | 1.00 | 32 | |||
ABA 10 mg/kg every four weeks + MTX | 99.0 | 75.0 | 55.8 | 9.7 | 16.5% | 60.0 | 30.8 | 21.3 | 62.1 | 60.1 | 62.1 | 1.00 | 29 | |||
ATTEST [15] | ABA 10 mg/kg every four weeks + MTX | 87.2 | 83.3 | 49.0 | 7.9 | 1.7 | 85.3 | 75.6 | 31.6 | 21.3 | nr | nr | nr | 1.80 | 31 | 49.4 |
PBO + MTX | 77.3 | 87.3 | 49.4 | 8.4 | 1.8 | 84.5 | 70.0 | 30.3 | 20.1 | 1.80 | 27 | 47.0 | ||||
INF 3 mg/kg every eight weeks +MTX | 84.8 | 82.4 | 49.1 | 7.3 | 1.7 | 86.1 | 71.5 | 31.7 | 20.3 | 1.70 | 33 | 47.8 | ||||
Adalimumab studies
| ||||||||||||||||
ARMADA [25] | PBO + MTX | mean IU/liter +- SD reported | 82.3 | 56.0 | 11.1 | 3.0 | nr | nr | 28.7 | 16.9 | 57.2 | 58.0 | 58.9 | 1.64 | 31 | nr |
ADA 20 mg every other week + MTX | 75.4 | 53.5 | 13.1 | 3.0 | 28.5 | 17.6 | 55.1 | 57.6 | 60.5 | 1.52 | 28 | |||||
Adalimumab 40 mg every other week + MTX | 74.6 | 57.2 | 12.2 | 2.9 | 28.0 | 17.3 | 53.0 | 56.9 | 58.7 | 1.55 | 21 | |||||
ADA 80 mg every other week + MTX | 75.3 | 55.5 | 12.8 | 3.1 | 30.3 | 17.0 | 55.0 | 58.8 | 62.6 | 1.55 | 28 | |||||
DE019 [24] | ADA 40 mg every other week + MTX | 81.6 | 76.3 | 56.1 | 11.0 | 2.4 | nr | nr | 27.3 | 19.3 | 55.9 | 52.7 | 62.0 | 1.45 | 18 | nr |
ADA 20 mg weekly + MTX | 81.2 | 75.5 | 57.3 | 11.0 | 2.4 | 27.9 | 19.6 | 55.2 | 51.9 | 61.6 | 1.44 | 14 | ||||
PBO + MTX | 89.5 | 73.0 | 56.1 | 10.9 | 2.4 | 28.1 | 19.0 | 56.3 | 54.3 | 61.3 | 1.48 | 18 | ||||
Certolizumab Pegol studies
| ||||||||||||||||
PBO + MTX | 82.8 | 83.9 | 52.2 | 6.2 | 1.4 | nr | nr | 29.8 | 21.2 | nr | nr | nr | 1.70 | 16 | 45.0 | |
CZP 200 mg every other week + MTX | 79.6 | 82.4 | 51.4 | 6.1 | 1.3 | 30.8 | 21.7 | 1.70 | 16 | 43.5 | ||||||
CZP 400 mg every other week + MTX | 83.6 | 83.6 | 52.4 | 6.2 | 1.3 | 31.1 | 21.5 | 1.70 | 14 | 42.5 | ||||||
PBO + MTX | 78.2 | 84.3 | 51.5 | 5.6 | 1.2 | nr | nr | 30.4 | 21.9 | 59.9 | 59.9 | 65.7 | 1.60 | 14 | 40.8 | |
CZP 200 mg every other week + MTX | 77.5 | 83.7 | 52.2 | 6.1 | 1.2 | 30.1 | 20.5 | 61.8 | 62.4 | 64.3 | 1.60 | 14 | 43.7 | |||
CZP 400 mg every other week + MTX | 75.5 | 78.0 | 51.9 | 6.5 | 1.3 | 30.0 | 21.0 | 60.5 | 61.1 | 62.8 | 1.60 | 13 | 39.1 | |||
Etanercept studies
| ||||||||||||||||
Weinblatt et al. 1999 [32] | PBO + MTX | 90.0 | 73.0 | 53.0 | 13.0 | 2.8 | 80.0 | 70.0 | 28.0 | 17.0 | 56.0 | 60.0 | 65.0 | 1.50 | 26 | 36.0 |
ETN 25 mg twice weekly + MTX | 84.0 | 90.0 | 48.0 | 13.0 | 2.7 | 75.0 | 53.0 | 28.0 | 20.0 | 50.0 | 60.0 | 60.0 | 1.50 | 22 | 25.0 | |
PBO + MTX | 71.0 | 79.0 | 53.0 | 6.8 | 2.3 | 86.0 | 64.0 | 33.1 | 22.6 | nr | nr | nr | nr | 26 | nr | |
ETN 25 mg twice weekly | 75.0 | 77.0 | 53.2 | 6.3 | 2.3 | 88.0 | 57.0 | 35.0 | 23.0 | 32 | ||||||
ETN 25 mg twice weekly + MTX | 76.0 | 74.0 | 52.5 | 6.8 | 2.3 | 88.0 | 62.0 | 34.2 | 22.1 | 30 | ||||||
Golimumab studies
| ||||||||||||||||
PBO + MTX | 81.2 | 82.0 | 52.0 | 6.5 | 70.74 | nr | nr | 21.0 | 12.0 | 57.0 | 53.0 | 56.5 | 1.25 | 8 | nr | |
GOL 100 mg every 4 weeks | 83.5 | 78.9 | 51.0 | 5.9 | 75.9 | 22.0 | 11.0 | 60.0 | 56.0 | 58.0 | 1.38 | 9 | ||||
GOL 50 mg every 4 weeks + MTX | 86.5 | 80.9 | 52.0 | 4.5 | 78.7 | 26.0 | 13.0 | 61.0 | 60.0 | 61.0 | 1.38 | 10 | ||||
GOL 100 mg every four weeks + MTX | 84.3 | 80.9 | 50.0 | 6.7 | 75.3 | 23.0 | 12.0 | 64.0 | 59.0 | 61.0 | 1.38 | 9 | ||||
Infliximab studies
| ||||||||||||||||
PBO + MTX | 77.0 | 80.0 | 51.0 | 8.9 | 2.5 | 72.0 | 64.0 | 24.0 | 19.0 | 67.0 | 62.0 | 65.0 | 1.80 | 30 | nr | |
INF 3 mg/kg every eight weeks +MTX | 84.0 | 81.0 | 56.0 | 8.4 | 2.8 | 79.0 | 63.0 | 32.0 | 19.0 | 70.0 | 66.0 | 61.0 | 1.80 | 31 | ||
INF 3 mg/kg every four weeks +MTX | 80.0 | 77.0 | 51.0 | 7.2 | 2.6 | 76.0 | 53.0 | 31.0 | 20.0 | 69.0 | 57.0 | 62.0 | 1.80 | 20 | ||
INF 10 mg/kg every eight weeks +MTX | 82.0 | 77.0 | 55.0 | 9.0 | 2.5 | 77.0 | 57.0 | 30.0 | 20.0 | 67.0 | 64.0 | 64.0 | 1.80 | 25 | ||
INF 10 mg/kg every four weeks +MTX | 82.0 | 73.0 | 52.0 | 8.7 | 2.5 | 68.0 | 65.0 | 35.0 | 23.0 | 66.0 | 60.0 | 60.0 | 1.50 | 24 | ||
Rituximab studies
| ||||||||||||||||
PBO + MTX | 100 (efficacy analyses) | 80.0 | 51.1 | 9.3 | 2.2 | nr | nr | 35.0 | 21.0 | nr | nr | nr | 1.70 | 33 | 40.0 | |
RTX 500 mg * two injections + MTX | 100 | 83.0 | 51.4 | 11.1 | 2.5 | 33.0 | 22.0 | 1.80 | 32 | 45.0 | ||||||
RTX 1,000 mg * two injections + MTX | 100 | 80.0 | 51.1 | 10.8 | 2.5 | 32.0 | 22.0 | 1.70 | 30 | 41.0 | ||||||
Edwards et al. 2004 [41] | PBO + MTX | 100 | 80.0 | 54.0 | 11.0 | 2.6 | nr | nr | 32.0 | 19.0 | nr | nr | nr | nr | 32 | 52.0 |
RTX 1,000 mg * two injections | 100 | 73.0 | 54.0 | 9.0 | 2.5 | 34.0 | 21.0 | 26 | 47.0 | |||||||
RTX 1,000 mg * two injections +cyclophosphamide | 100 | 83.0 | 53.0 | 10.0 | 2.6 | 33.0 | 19.0 | 40 | 55.0 | |||||||
RTX 1,000 mg * two injections + MTX | 100 | 75.0 | 54.0 | 12.0 | 2.5 | 32.0 | 23.0 | 29 | 53.0 | |||||||
Tocilizumab studies
| ||||||||||||||||
PBO + MTX | 78.0 | 78.0 | 50.6 | 7.8 | 1.7 | 68.0 | nr | 32.8 | 20.7 | 57.3 | 63.6 | 63.7 | 1.50 | 24 | 49.7 | |
TCZ 4 mg/kg every four weeks + MTX | 83.0 | 82.0 | 51.4 | 7.4 | 1.5 | 68.0 | 33.2 | 20.0 | 60.7 | 65.6 | 63.6 | 1.60 | 28 | 49.2 | ||
TCZ 8 mg/kg every four weeks + MTX | 71.0 | 85.0 | 50.8 | 7.5 | 1.5 | 66.0 | 31.9 | 19.5 | 59.9 | 64.8 | 64.0 | 1.60 | 26 | 51.2 | ||
LITHE [42] | PBO + MTX | nr | nr | nr | nr | nr | nr | nr | nr | nr | nr | nr | nr | 1.5 | nr | nr |
TCZ 4 mg/kg every four weeks + MTX | 1.5 | |||||||||||||||
TCZ 8 mg/kg every four weeks + MTX | 1.5 |
Trial | N | Mean HAQ CFB at 24 weeks (SD) | Mean HAQ CFB at 52 weeks (SD) | ACR-50 r at 24 weeks | ACR-50 r at 52 weeks | DAS28 < 2.6 r at 24 weeks | DAS28 < 2.6 r at 52 weeks |
---|---|---|---|---|---|---|---|
Placebo + MTX
| |||||||
219 | -0.40 (0.59) | -0.37 (0.59) | 37 | 40 | 6 | 4 | |
119 | -0.14 (0.49*) | -0.10 (0.83*) | 14 | 24 | 11 | 12 | |
ATTEST [15] | 110 | -0.29 (0.22) | 22 | 3 | |||
ARMADA [25] | 62 | -0.27 (0.57) | 5 | ||||
DE019 [24] | 200 | -0.24 (0.52) | -0.25 (0.56) | 19 | 19 | ||
199 | -0.17 (0.56) | -0.18 (0.56) | 15 | 15 | |||
127 | -0.14 (0.45) | 4 | 1 | ||||
Weinblatt et al. 1999 [32] | 30 | -0.40 (0.49*) | 1 | ||||
228 | -0.63 (1.08*) | -0.63 (1.41*) | 92 | 91 | 31 | 39 | |
133 | -0.13 (0.58) | 18 | 8 | ||||
88 | -0.19 (0.49*) | -0.17 (0.60*) | 8 | ||||
122 | -0.28 (0.50) | 16 | |||||
Strand et al. 2006 [41] | 40 | -0.40 (0.62*) | -0.30 (0.64*) | 5 | 2 | ||
172 | -0.19 (0.56*) | -0.19† (0.60*) | 15 | 15 | 3 | 3 | |
204 | -0.34 (0.83*) | 22 | 1 | ||||
LITHE [42] | 393 | 39 | 12 | ||||
Abatacept + MTX
| |||||||
433 | -0.59 (0.62) | -0.66 (0.62) | 173 | 209 | 64 | 103 | |
115 | -0.42 (0.49*) | -0.47 (0.83*) | 42 | 48 | 30 | 40 | |
ATTEST [15] | 156 | -0.68 (0.22) | -0.67 (0.62) | 63 | 71 | 18 | 29 |
Adalimumab + MTX
| |||||||
ARMADA [25] | 67 | -0.62 (0.63) | 37 | ||||
DE019 [24] | 207 | -0.56 (0.52) | -0.59 (0.57) | 81 | 86 | ||
Certolizumab + MTX
| |||||||
393 | -0.58 (0.59) | -0.60 (0.59) | 146 | 147 | |||
246 | -0.50 (0.47) | 80 | 23 | ||||
Etanercept + MTX
| |||||||
Weinblatt et al. 1999 [32] | 59 | -0.70 (0.49*) | 23 | ||||
231 | -0.89 (1.08*) | -0.97 (1.41*) | 136 | 180 | 70 | 88 | |
Golimumab + MTX
| |||||||
89 | -0.47 (0.55) | 33 | 18 | ||||
Infliximab + MTX
| |||||||
ATTEST [15] | 165 | -0.53 (0.29) | -0.59 (0.64) | 61 | 60 | 21 | 20 |
86 | -0.31 (0.49*) | -0.32 (0.60*) | 21 | ||||
Rituximab + MTX
| |||||||
122 | -0.49 (0.55) | 41 | |||||
Strand et al. 2006 [41] | 40 | -0.60 (0.92*) | -0.60 (0.88*) | 17 | 14 | ||
170 | -0.42 (0.54*) | -0.47 (0.60*) | 44 | 61 | 15 | 19 | |
Tocilizumab + MTX
| |||||||
205 | -0.55 (0.82*) | 90 | 47 | ||||
LITHE [42] | 398 | 145 | 127 |
Network Meta-analysis results (Tables 4 and 5)
HAQ change from baseline at 24 and 52 weeks
Treatment effect relative to Abatacept + MTX | Difference in mean HAQ CFB at 24/26 weeks (95% CrL)* | Difference in mean HAQ CFB at 48/54 weeks (95% CrL)** | OR for ACR-50 at 24/26 weeks (95% CrL)* | OR for ACR-50 at 48/54 weeks (95% CrL)** | OR for DAS28 < 2.6 at 24/26 weeks (95% CrL)* | OR for DAS28 < 2.6 at 48/54 weeks (95% CrL)* |
---|---|---|---|---|---|---|
Placebo + MTX | -0.30 (-0.41; -0.18) | -0.29 (-0.38; -0.21) | 3.37 (1.49; 8.06) | 3.84 (2.84; 5.26) | 4.77 (1.60; 15.78) | 8.82 (1.50; 57.83) |
Adalimumab + MTX | 0.03 (-0.16; 0.24) | 0.05 (-0.09; 0.18) | 0.40 (0.09; 1.50) | 0.56 (0.29; 1.03) | ||
Certolizumab Pegol + MTX | 0.08 (-0.09; 0.28) | 0.13 (-0.00; 0.26) | 0.35 (0.08; 1.33) | 0.51 (0.26; 0.96) | 0.26 (0.01; 3.90) | |
Etanercept + MTX | -0.02 (-0.24; 0.21) | 0.05 (-0.22; 0.32) | 1.05 (0.17; 3.24) | 0.72 (0.43; 1.19) | 1.69 (0.21; 15.80) | 2.94 (0.14; 67.12) |
Golimumab + MTX | 0.04 (-0.21; 0.30) | 0.87 (0.16; 5.15) | 1.18 (0.13; 11.66) | |||
Infliximab + MTX | -0.11 (-0.29; 0.08) | -0.11 (-0.22; 0.01) | 1.31 (0.27; 7.61) | 1.40 (0.93; 2.10) | 0.88 (0.09; 7.76) | 1.68 (0.14; 21.23) |
Rituximab + MTX | -0.09 (-0.31; 0.14) | 0.01 (-0.34; 0.35) | 0.85 (0.20; 3.47) | 0.31 (0.04; 1.37) | ||
Tocilizumab + MTX | -0.09 (-0.35; 0.18) | 0.51 (0.10; 2.88) | 0.05 (0.00; 0.79) |
Treatments relative to effect | Absolute HAQ CFB at 24/26 weeks (95% CrL)* | Absolute HAQ CFB at 48/54 weeks (95% CrL)** | Proportion (%) of patients with ACR-50 at 24/26 weeks (95% CrL) * | Proportion (%) of patients with ACR-50 at 48/54 weeks (95% CrL)** | Proportion (%) of patients with DAS28 < 2.6 at 24/26 weeks (95% CrL)* | Proportion (%) of patients with DAS28 < 2.6 at 48/54 weeks (95% CrL)* |
---|---|---|---|---|---|---|
Placebo + MTX | -0.29 (-0.31; -0.26) | -0.29 (-0.34; -0.24) | 11.9% (9.7%; 14.0%) | 12.5% (9.4%; 15.5%) | 2.6% (1.4%; 4.1%) | 7.0% (4.7%; 9.8%) |
Adalimumab + MTX | -0.61 (-0.77; -0.46) | -0.63 (-0.74; -0.51) | 53.5% (28.0%; 77.9%) | 49.5% (35.9%; 63.5%) | ||
Certolizumab Pegol + MTX | -0.67 (-0.82; -0.53) | -0.71 (-0.81; -0.61) | 57.3% (31.2%; 79.9%) | 51.7% (38.1%; 66.1%) | 33.4% (4.4%; 90.0%) | |
Etanercept + MTX | -0.56 (-0.75; -0.38) | -0.63 (-0.87; -0.39) | 30.7% (15.6%; 65.2%) | 43.2% (31.8%; 54.9%) | 6.9% (1.0; 31.5%) | 18.7% (1.8%; 73.3%) |
Golimumab + MTX | -0.63 (-0.86; -0.39) | 34.6% (9.7%; 69.2%) | 9.6% (1.4%; 42.4%) | |||
Infliximab + MTX | -0.48 (-0.62; -0.33) | -0.48 (-0.59; -0.36) | 26.0% (6.6%; 57.4%) | 28.1% (19.4%; 38.3%) | 12.6% (1.9%; 53.3%) | 28.8% (1.9%; 89.5%) |
Rituximab + MTX | -0.49 (-0.68; -0.31) | -0.59 (-0.91; -0.27) | 35.3% (14.8%; 61.9%) | 64.1% (32.4%; 91.3%) | ||
Tocilizumab + MTX | -0.49 (-0.73; -0.26) | 47.5% (16.1%; 78.6%) | 71.0% (19.0%; 98.9%) | |||
Abatacept + MTX | -0.58 (-0.70; -0.46) | -0.58 (-0.66; -0.50) | 31.7% (15.9%; 50.6%) | 35.4% (27.3%; 43.3%) | 11.3% (3.7%; 28.8%) | 40.2% (10.4%; 80.3%) |