Table 2.
| Trial | Notes | Phase | Patient Population | Rx regimen | ACR20 TOFA | Other measures |
AEs | Serious AEs | Infectionn TOFA (serious infection TOFA) |
|---|---|---|---|---|---|---|---|---|---|
| Kremer A&R 2009 | 2a | RA with inadequate responses to MTX or ETA, ADA, INF (most were MTX failures) | PBO vs TOFA 5mg BID vs 15mg BID vs 30mg BID × 6 weeks à DC for 6 weeks with followup | 5mg: 70.5% 15mg: 80.2% 30mg: 76.8% PBO: 29.2% |
ACR50/70, HAQ-DI, DAS28-ESR, DAS28-CRP | 5mg: 59% 15mg: 75% 30mg: 77% PBO: 59% |
5mg: none 15mg: 1 patient 30mg: 1 patient PBO: 1 patient |
5mg: 24.6% 15mg: 30.4% 30mg: 30.4% PBO: 26.2% |
|
| Tanaka 2011 | 2b | MTX failures (Note low dose of background MTX avg 8mg weekly) | Background MTX vs MTX + TOFA 1mg BID vs 3mg BID vs 5mg BID vs 10 mg BID × 12 weeks | 1mg = 64.3% 3mg =77.8% 5mg = 96.3 10mg = 80.8% PBO 14.3% |
ACR50/70, HAQ-DI, DAS28-CRP | 1mg: 53.6% 3mg: 48.1% 5mg: 77.7% 10mg: 73.4% PBO: 35.8% |
1mg: 1 patient 3mg: 1 patient 5mg: 1 patient 10mg: 2 patients PBO: none |
1mg = 10.7% 3mg =29.6% 5mg = 11.1% 10mg = 42.3% PBO 21.4% |
|
| Kremer 2011 ACR | ORAL Sync, Abstract only | 3 | Failed nonbiologic DMARDs | Monotherapy with TOFA 5mg BID × 12mo vs 10mg BID × 12 mo vs PBO → TOFA 5mg or 10mg after 3mo for nonresponders and 6mo for all patients. Abstract reprsents 6mo interim analysis | 5mg = 52.7% 10mg =58.3% PBO: 31.2% |
ACR50/70, HAQ-DI, DAS28-ESR |
Months 0–3 5mg: 52.7% 10mg: 54.4% PBO: 61% Months 3–6 5mg: 38.4% 10mg: 39% PBO: 25.9% |
Months 0–3 5mg: 2.9% 10mg: 2.5% PBO: 3.8% Months 3–6 5mg: 1.6% 10mg: 2.2% PBO: 0% |
Four opportunistic infections. Serious infectious events in 3 (5mg BID) and 5 (10mg BID) patients from months 0–6. No data in PBO-treated patients. |
| Fleischmann 2012 A&R | 2b | Failed DMARDs (mainly MTX failures at mod/approp doses 10–15mg weekly) | Monotherapy with TOFA 1mg BID vs 3mg BID vs 5mg BID vs 10mg BID vs 15mg BID vs ADA 40mg every 14d × 12 weeks followed by TOFA 5mg BID for 12 weeks | 1mg: 31.5% 3mg: 39.2% 5mg: 59.2% 10mg: 70.5% 15mg: 71.9% PBO: 22% ADA (wk 12): 35.9% |
ACR50/70, HAQ-DI, SF-36, FACIT-F, DAS28-ESR, DAS28-CRP | 1mg: 51.4% 3mg: 52.9% 5mg: 55.1% 10mg: 59% 15mg: 61.4% PBO: 47.1% ADA (wk12): 50.9% ADA→TOFA (wk24): 63.6% |
1mg: 5.4% 3mg: 2.9% 5mg: 0% 10mg: 1.6% 15mg: 7% PBO: 5.9% ADA (wk12): 1.9% ADA→TOFA (wk24): 9.1% |
1mg: 29.7% (5.9%) 3mg: 20.6% (0%) 5mg: 34.7% (0%) 10mg: 34.3% (0%) 15mg: 33.3% (1.8%) PBO: 17.6% (2.9%) ADA (wk12): 18.9% (0%) ADA→TOFA (wk24): 25% (2.3%) |
|
| Kremer 2012 A&R | 2b | MTX failures | MTX background + TOFA 20mg daily vs 1mg BID vs 3mg BID vs 5mg BID vs 10mg BID vs 15mg BID × 24 weeks | 1mg: ???% 3mg: 52.9% 5mg: 50.7% 10mg: 58.1% 15mg: 56.0% 20mg: 53.8% PBO: 33.3% |
ACR50/70, HAQ-DI, DAS28-CRP | 1mg: 59.2% 3mg: 69.1% 5mg: 66.2% 10mg: 67.6% 15mg: 76% 20mg: 61.2% PBO: 56.9% |
1mg: 2% 3mg: 7.3% 5mg: 5.6% 10mg: 1.4% 15mg: 8% 20mg: 6% PBO: 0% |
1mg: 14.3% (0%) 3mg: 20% (0%) 5mg: 22.5% (1.4%) 10mg: 17.6% (1.4%) 15mg: 18.7% (0%) 20mg: 19.4% (1.5%) PBO: 5.9% (0%) |
|
| Van Vollenhoven 2012 NEJM | ORAL Standard | 3 | MTX failures | MTX background in all groups + TOFA 5mg BID × 12 mo vs TOFA 10mg BID × 12 mo vs ADA 40mg q2weeks × 12 mo vs PBO → nonresponders switched to TOFA 5mg or 10mg BID at mo3 and all patients switched to TOFA 5mg or 10mg BID at mo6 | 5mg: 51.5% 10mg: 52.6% PBO: 28.3% ADA: 47.2% |
ACR50/70, HAQ-DI, DAS28-ESR, DAS28-CRP |
Months 0–3 5mg: 52% 10mg: 46.8% PBO: 47.2% ADA: 51.5% Months 3–6 5mg: 32.8% 10mg: 30.8% PBO: 27.1% PBO→5mg: 25% PBO→10mg: 42.9% ADA: 33.3% Months 6–12 5mg: 43.6% 10mg: 41.8% PBO→5mg: 32.1% PBO→10mg: 40.4% ADA: 40.7% |
Months 0–3 5mg: 5.9% 10mg: 5% PBO: 1.9% ADA: 2.5% Months 3–6 5mg: 4.9% 10mg: 3.5% PBO: 3.4% PBO→5mg: 0% PBO→10mg: 0% ADA: 2.9% Months 6–12 5mg: 4.9% 10mg: 3% PBO→5mg: 1.8% PBO→10mg: 7.7% ADA: 3.4% |
(Serious only) Months 0–3 5mg: 1.5% 10mg: 2% PBO: 0.9% ADA: 0% Months 3–6 5mg: 1% 10mg: 0.5% PBO: 0% PBO→5mg: 0% PBO→10mg: 0% ADA: 1% Months 6–12 5mg: 1% 10mg: 1.5% PBO→5mg: 0% PBO→10mg: 1.9% ADA: 0.5% |
| Fleischmann 2012 NEJM | ORAL Solo | 3 | DMARD or biologic nonresponders, about 80% methotrexate failures | Monotherapy with TOFA 5mg BID × 6 mo vs TOFA 10mg BID × 6 mo vs PBO × 3mo → TOFA 5mg BID × 3 mo vs PBO × 3mo → TOFA 10mg BID × 3 mo | 5mg: 59.8% 10mg: 65.7% PBO: 26.7% |
ACR50/70, HAQ-DI, DAS28-ESR, FACIT-F |
Months 0–3 5mg: 51% 10mg: 56.7% PBO: 54.9% Months 3–6 5mg: 39.9% 10mg: 41.2% PBO→5mg: 36.1% PBO→10mg: 39.3% |
Months 0–3 5mg: 0.4% 10mg: 2% PBO: 4.9% Months 3–6 5mg: 2.1% 10mg: 2.4% PBO→5mg: 1.6% PBO→10mg: 0% |
(Serious only) Months 0–3 5mg: 0% 10mg: 0.4% PBO: 0% Months 3–6 5mg: 0.4% 10mg: 1.2% PBO→5mg: 1.6% PBO→10mg: 0% |
| Burmester 2012 Lancet | ORAL Step | 3 | TNFi nonresponders only, 30% had failed 2 + TNFis | MTX background in all groups + TOFA 5mg BID × 6 mo vs TOFA 10mg BID × 6 mo vs PBO × 3mo → TOFA 5mg BID × 3 mo vs PBO × 3mo → TOFA 10mg BID × 3 mo | 5mg: 41.7% 10mg: 48.1% PBO: 24.4% |
ACR50/70, HAQ-DI, DAS28-ESR, DAS28-CRP, FACIT-F |
Months 0–3 5mg: 53.4% 10mg: 56.7% PBO: 56.8% Months 3–6 5mg: 42.9% 10mg: 43.3% PBO→5mg: 36.4% PBO→10mg: 42.4% |
Months 0–3 5mg: 1.5% 10mg: 1.5% PBO: 4.5% Months 3–6 5mg: 3.8% 10mg: 4.5% PBO→5mg: 4.5% PBO→10mg: 3% |
(Serious only) Months 0–3 5mg: 0% 10mg: 0% PBO: 0% Months 3–6 5mg: 1.5% 10mg: 1.5% PBO→5mg: 1.5% PBO→10mg: 0% |
| Lee 2012 ACR | ORAL Start. Abstract only (interim analysis) | 3 (ongoing) | MTX naïve patients | TOFA 5mg BID vs. 10mg BID vs MTX 10mg/week titrated up to 20mg/week; patients treated × 24 mo (data from 12 mo interim analysis) | 5mg: 71% 10mg: 75.8% MTX: 50.5% |
ACR50/70, HAQ-DI, Sharp-van der Hejide Score (SHS) | 5mg: 70.1% 10mg: 74.4% MTX: 69.9% |
5mg: 6.5% 10mg: 6.1% MTX: 7% |
5mg: 31.8% 10mg: 38.7% MTX: 27.4% |
| Van der Hejide 2013 A&R | ORAL Scan | 3 | Active erosive RA with erosive disease, MTX failures (10–20% failed biologics) | MTX background in all groups + TOFA 5mg BID × 24 mo vs TOFA 10mg BID × 24 mo vs PBO → nonresponders switched to TOFA 5mg or 10mg BID at mo3 and all patients switched to TOFA 5mg or 10mg BID at mo6 |
At month 6 5mg: 51.5% 10mg: 61.8% PBO: 25.3% At month 12 5mg: 48.5% 10mg: 57% |
ACR50/70, HAQ-DI, DAS28-ESR, Sharp-van der Hejide Score (SHS), FACIT-F |
Months 0–3 5mg: 48.9% 10mg: 54.1% PBO: 45.6% Months 3–6 5mg: 45.2% 10mg: 35.1% PBO→5mg: 42.9% PBO→10mg: 40.5% Months 6–12 5mg: 51.7% 10mg: 55.1% PBO→5mg: 42% PBO→10mg: 44.3% |
Months 0–3 5mg: 3.7% 10mg: 3.2% PBO: 3.1% Months 3–6 5mg: 5.3% 10mg: 2.2% PBO→5mg: 2.4% PBO→10mg: 2.7% Months 6–12 5mg: 4% 10mg: 2.8% PBO→5mg: 1.2% PBO→10mg: 5.1% |
Months 0–3 5mg: 0.6% 10mg: 0.6% PBO: 0% Months 3–6 5mg: 2.5% 10mg: 0.6% PBO→5mg: 1.2% PBO→10mg: 1.3% Months 6–12 5mg: 0.3% 10mg: 0.3% PBO→5mg: 0% PBO→10mg: 1.3% |