Table 1.
Methods and outcomes reported in randomized controlled trials for tofacitinib in RA therapy
| References | Study groups | Inclusion criteriaa | Concomitant therapy | ACR20b | ACR50b |
|---|---|---|---|---|---|
| Tofacitinib vs placebo | |||||
| Burmester et al28 | Placebo followed by tofacitinib 5 mg BID (n=66) Placebo followed by tofacitinib 10 mg BID (n=66) Tofacitinib 5 mg BID (n=133) Tofacitinib 10 mg BID (n=134) |
Inadequate response to TNF inhibitors MTX administration |
Antimalarials Corticosteroids |
(Month 3) 1. Tofacitinib 5 mg vs placebo: 41.7 vs 24.4% (P=0.0024) 2. Tofacitinib 10 mg vs placebo: 48.1 vs 24.4% (P<0.0001) |
(Month 3) 1. Tofacitinib 5 mg vs placebo: 26.5 vs 8.4% (P<0.0001) 2. Tofacitinib 10 mg vs placebo: 27.8 vs 8.4% (P<0.0001) |
| Fleischmann et al30 | Placebo followed by tofacitinib 5 mg BID (n=61) Placebo followed by tofacitinib 10 mg BID (n=61) Tofacitinib 5 mg BID (n=243) Tofacitinib 10 mg BID (n=245) |
Inadequate response to at least one nonbiologic or biologic DMARD | Antimalarials Corticosteroids |
(Month 3) 1. Tofacitinib 5 mg vs placebo: 59.8 vs 26.7% (P<0.001) 2. Tofacitinib 10 mg vs placebo: 65.7 vs 26.7% (P<0.001) |
(Month 3) 1. Tofacitinib 5 mg vs placebo: 31.1 vs 12.5% (P<0.001) 2. Tofacitinib 10 mg vs placebo: 36.8 vs 12.5% (P<0.001) |
| van der Heijde et al24 | Placebo followed by tofacitinib 5 mg BID (n=81) Placebo followed by tofacitinib 10 mg BID (n=79) Tofacitinib 5 mg BID (n=321) Tofacitinib 10 mg BID (n=316) |
1. Three distinct joint erosions on posteroanterior hand and wrist 2. Stable doses of MTX were required 3. Stable doses of low-dose corticosteroids and NSAIDs were allowed |
(Month 6) 1. Tofacitinib 5 mg vs placebo: 51.5 vs 25.3% (P<0.0001) 2. Tofacitinib 10 mg vs placebo: 61.8 vs 25.3% (P<0.0001) |
(Month 6) 1. Tofacitinib 5 mg vs placebo: 32.4 vs 8.4% (P<0.0001) 2. Tofacitinib 10 mg vs placebo: 43.7 vs 8.4% (P<0.0001) |
|
| Kremer et al32 | Placebo followed by tofacitinib 5 mg BID (n=79) Placebo followed by tofacitinib 10 mg BID (n=80) Tofacitinib 5 mg BID (n=315) Tofacitinib 10 mg BID (n=318) |
1. Inadequate response to treatment with ≥1 stably dosed nonbiologic or biologic DMARDs before baseline; continue treatment with one or more background nonbiologic DMARDs at stable doses throughout the study 2. MTX administration; background, low-dose, oral corticosteroid therapy with stable dosing (prednisone ≤10 mg daily or equivalent) was permitted |
Background DMARDs MTX Oral corticosteroids |
(Month 6) 1. Tofacitinib 5 mg vs placebo: 52.1 vs 30.8% (P<0.001) 2. Tofacitinib 10 mg vs placebo: 56.6 vs 30.8% (P<0.001) Tofacitinib vs placebo; difference percentage points: (month 6) 5 mg 28.7%; P<0.001 10 mg 30.3%; P<0.001 |
(Month 6) Tofacitinib vs placebo; difference in percentage points: 5 mg 22.1%; P<0.001 10 mg 24.8%; P<0.001 |
| Kremer et al33 | Placebo (n=65) Tofacitinib 5 mg BID (n=61) Tofacitinib 15 mg BID (n=69) Tofacitinib 30 mg BID (n=69) |
1. All patients met the ACR 1991 revised criteria for global functional status in RA of class I, II, or III 2. Inadequate response to, or discontinued therapy due to unacceptable toxicity from, MTX, etanercept, infliximab, or adalimumab 3. Patients who discontinue all previous DMARD required suitable washout |
Corticosteroids | (Week 6) Tofacitinib 5 mg vs placebo: 70.5 vs 29.2% (P<0.001) |
(Week 6) Tofacitinib 5 mg increased response rates relative to placebo (P<0.001) |
| Kremer et al34 | Placebo (n=69) Tofacitinib 1 mg BID (n=71)c Tofacitinib 3 mg BID (n=68) Tofacitinib 5 mg BID (n=71) Tofacitinib 10 mg BID (n=75)c Tofacitinib 15 mg BID (n=75) Tofacitinib 20 mg/day (n=80) |
1. Patients must have been receiving oral or parenteral MTX continuously for ≥4 months 2. All other biologic or nonbiologic DMARDs and immunosuppressive therapy were discontinued ≥4 weeks prior to the study |
Corticosteroids | (Week 12) 1. Tofacitinib 5 mg vs placebo: 50.7 vs 33.3% (P≤0.05) 2. Tofacitinib 10 mg vs placebo: 58.1 vs 33.3% (P≤0.05) (Week 24) 1. Tofacitinib 5 mg (29.0%) was higher vs placebo (P>0.05) 2. Tofacitinib 10 mg (22.6%) was significantly higher vs placebo (P≤0.05) |
(Week 12) Tofacitinib 5 mg increased response rates relative to placebo (P≤0.05) |
| Tanaka et al36 | Placebo (n=28) Tofacitinib 1 mg BID (n=28)c Tofacitinib 3 mg BID (n=27)c Tofacitinib 5 mg BID (n=27)c Tofacitinib 10 mg BID (n=26)c |
1. Inadequate clinical response to MTX; all patients were required to remain on stable background MTX 6 mg/week 2. All other traditional and biologic DMARDs and immunosuppressive therapy were discontinued at least 4 weeks prior to the study |
Low-dose corticosteroids | (Week 12) 1. Tofacitinib 5 mg vs placebo: 96.3 vs 14.3% (P<0.0001) 2. Tofacitinib 10 mg vs placebo: 80.8 vs 14.3% (P<0.0001) |
(Week 12) Tofacitinib treatment had significantly greater effect vs placebo: 5 mg (P<0.0001), 10 mg (P<0.001) |
| Tofacitinib vs MTX | |||||
| Lee et al35 | Tofacitinib 5 mg BID (n=373) Tofacitinib 10 mg BID (n=397) MTX (n=186) |
≥3 distinct joint erosions detected on hand and wrist or foot radiographs or a positive test for IgM rheumatoid factor or antibodies to cyclic citrullinated peptide | (Month 24) Tofacitinib 5 mg: 64.2% Tofacitinib 10 mg: 64.2% MTX: 42.4% Tofacitinib 5 and 10 mg for the comparison with MTX (P<0.001) |
(Month 24) Tofacitinib 5 mg: 49.3% Tofacitinib 10 mg: 49.2% MTX: 28.3% Tofacitinib 5 and 10 mg for the comparison with MTX (P<0.001) |
|
| Tofacitinib or adalimumab vs placebo | |||||
| Fleischmann et al29 | Placebo (n=59) Tofacitinib 1 mg BID (n=54) Tofacitinib 3 mg BID (n=51) Tofacitinib 5 mg BID (n= 49) Tofacitinib 10 mg BID (n=61) Tofacitinib 15 mg BID (n=57) Adalimumab 40 mg qow (n=53) |
Failure of at least one DMARD due to lack of efficacy or toxicity and washout of all DMARDs except antimalarial agents at stable doses | Antimalarials Corticosteroids |
(Week 24) 1. Tofacitinib 5 mg vs placebo: 51.0 vs 25.4% (P≤0.05) 2. Tofacitinib 10 mg vs placebo: 65.6 vs 25.4% (P<0.0001) |
(Week 24) 1. Tofacitinib 5 mg vs placebo: 34.7 vs 10.2% (P≤0.05) 2. Tofacitinib 10 mg vs placebo: 44.3 vs 10.2% (P<0.0001) |
| van Vollenhoven et al27 | Placebo followed by tofacitinib 5 mg BID (n=56) Placebo followed by tofacitinib 10 mg BID (n=52) Tofacitinib 5 mg BID (n=204) Tofacitinib 10 mg BID (n=201) Adalimumab 40 mg q2w (n=204) |
Patients were receiving 7.5–25 mg of MTX weekly and had an incomplete response | Corticosteroids | (Month 6) 1. Tofacitinib 5 mg vs placebo: 51.5 vs 28.3% (P<0.0001) 2. Tofacitinib 10 mg vs placebo: 52.6 vs 28.3% (P<0.001) |
(Month 6) Significantly greater responses were seen with the active treatments than with placebo (P≤0.05) |
| Tofacitinib monotherapy vs tofacitinib and MTX vs adalimumab and MTX | |||||
| Fleischmann et al31 | Tofacitinib 5 mg BID monotherapy (n=384) Tofacitinib 5 mg BID and MTX (n=376) Adalimumab 40 mg qow and MTX (n=386) |
1. Classes I–III functional capacity as classified by the ACR 1991 revised criteria for RA 2. Inadequate responders to MTX treatment 3. Patients were required to discontinue all conventional synthetic DMARDs other than MTX but could continue to receive stable nonsteroidal anti-inflammatory drugs, analgesics, or oral corticosteroids or a combination |
Corticosteroid use at baseline | (Month 12) 1. Tofacitinib monotherapy: 39% 2. Tofacitinib and MTX: 48% 3. Adalimumab and MTX: 46% |
|
Notes: ACR20 indicates that symptoms have improved 20% from baseline. ACR50 indicates that symptoms have improved 50% from baseline.
a
Inclusion criteria in all studies were as follows: at least 18 years old and active moderate-to-severe RA based on the ACR 1987 revised criteria.
b
The results were presented only for registered doses of tofacitinib (5 mg and 10 mg BID).
c
Randomized and treated patients.
Abbreviations: ACR, American College of Rheumatology; BID, twice a day; DMARDs, disease-modifying antirheumatic drugs; MTX, methotrexate; NSAIDs, nonsteroidal anti-inflammatory drugs; q2w, every 2 weeks; qow, once every other week; RA, rheumatoid arthritis; TNF, tumor necrosis factor.