Background
Methods
Inclusion criteria
Outcome measures
Data extraction
Methodological quality assessment
Statistical analysis
Results
Search results and study selection
Article | Region | Study duration, weeks | Possible concomitant medication | Dose of tofacitinib | No of patients randomiseda
| Mean DAS28-3(CRP)a
| Mean DAS28-4(ESR)a
| Mean HAQ-DIa
| Mean no of swollen jointsa
| Mean no of tender jointsa
|
---|---|---|---|---|---|---|---|---|---|---|
Fleischmann 2012a [21] | United States; Europe; Latin American; the Republic of Korea | 24 | NSAIDs; antimalarial agents; opioids; acetaminophen; oral glucocorticoids | 1, 3, 5, 10, 15 mg bid | Total: 386 | Placebo:5.6 | Placebo:6.6 | Placebo:1.54 | Placebo:16.9 | Placebo:25.9 |
Placebo: 59 | ||||||||||
tofacitinib: 54, 51, 49, 61, 57 | tofacinitib: 5.5, 5.4, 5.6, 5.5, 5.5 | tofacinitib: 6.5, 6.4, 6.6, 6.5, 6.5 | tofacinitib: 1.57, 1.53, 1.40, 1.49, 1.62 | tofacinitib: 16.7, 15.9, 17.4, 16.3, 16.9 | tofacinitib: 27.0, 24.6, 27.1, 25.7, 25.9 | |||||
adalimumab 40 mg qow: 53 | adalimumab 40 mg qow: 5.4 | adalimumab 40 mg qow: 6.3 | adalimumab 40 mg qow: 1.44 | adalimumab 40 mg qow: 14.9 | adalimumab 40 mg qow: 24.1 | |||||
Randomised but not treated: 2 | ||||||||||
Fleischmann 2012b [25] | United States; Europe; Latin America; Asia | 24 | NSAIDs; glucocorticoids; | 5, 10 mg bid | Total: 611 | Placebo: 5.56 | Placebo: 6.65 | Placebo: 1.53 | Placebo: 17.3 | Placebo: 28.9 |
Placebob: 61, 61 | tofacitinib: 5.68, 5.60 | tofacitinib: 6.71, 6.70 | tofacitinib: 1.53, 1.50 | tofacitinib: 16.3, 17.0 | tofacitinib: 29.4, 29.1 | |||||
tofacitinib:243, 245 | ||||||||||
Randomised but not treated: 1 | ||||||||||
Kremer 2009 [20] | United States; Canada; Europe; Latin American | 6 (treatment)?+?6 (follow-up) | NSAIDs; selective COX-2 inhibitors; opioids; acetaminophen; oral glucocorticoids | 5, 15, 30 mg bid | Total: 264 | Placebo: 6.0 | NA | Placebo: 1.7 | Placebo: 20.01 | Placebo: 30.3 |
Placebo: 65 | ||||||||||
tofacitinib: 61, 69, 69 | tofacitinib: 6.2, 5.7, 5.9 | tofacitinib: 1.7, 1.6, 1.6 | tofacitinib: 21.1, 16.2, 19.5 | tofacitinib: 32.3, 26.7, 29.3 | ||||||
Kremer 2012 [19] | United States; Europe; Latin America | 24 | MTX (compulsory) | 1, 3, 5, 10, 15 mg bid, 20 mg qd | Total: 509 | Placebo: 5.3 | Placebo: 6.1 | Placebo: 1.20 | Placebo: 15.7 | Placebo: 21.6 |
Placebo: 69 | tofacitinib: 5.5, 5.3, 5.1, 5.3, 5.4 | tofacitinib: 6.4, 6.1, 6.1, 6.4, 6.2 | tofacitinib: 1.58, 1.36, 1.44, 1.33, 1.41 | tofacitinib: 6.5, 15.7, 14.1, 14.7, 15.3 | tofacitinib: 23.6, 22.8, 21.5, 24.8, 23.7 | |||||
tofacitinib: 70, 68, 71, 74, 75 | 20 mg qd: 5.3 | 20 mg qd: 6.3 | 20 mg qd: 1.46 | 20 mg qd: 15.2 | 0 mg qd: 23.1 | |||||
20 mg qd: 80Randomised but not treated: 2 | ||||||||||
Tanaka 2011 [18] | Japan | 12 | MTX supplemented with folic acid (compulsory); | 1, 3, 5, 10 mg bid | Total: 140 | Placebo: 4.9 | Placebo: 5.9 | Placebo: 1.3 | Placebo: 13.8 | Placebo: 16.4 |
Placebo: 28 | ||||||||||
tofacitinib: 28, 27, 27, 26 | tofacitinib: 5.0, 5.1, 5.0, 4.9 | tofacitinib: 6.1, 6.1, 6.0, 5.9 | tofacitinib: 1.1, 1.3, 1.2, 1.2 | tofacitinib: 13.2, 15.1, 15.6, 15.1 | tofacitinib: 16.4, 16.2, 17.8, 15.4 | |||||
NSAIDs;selective COX-2 inhibitors; glucocorticoids | Randomised but not treated: 4 | |||||||||
van Vollenhoven2012 [22] | North America; Latin America; Europe; etc. | 52 | MTX (compulsory) 5, 10 mg bid | Total: 717 | Placeboc: 5.6, 5.3 | Placeboc: 6.6, 6.3 | Placeboc: 1.5, 1.4 | Placeboc: 16.9, 16.4 | Placeboc: 26.6, 28.1 | |
Placeboc: 56, 52 | tofacitinib: 5.4, 5.4 | tofacitinib: 6.6, 6.5 | tofacitinib: 1.5, 1.5 | tofacitinib: 16.7, 15.8 | tofacitinib: 28.5, 26.1 | |||||
tofacitinib: 204, 201 | adalimumab 40 mg qow: 5.3 | adalimumab 40 mg qow: 6.4 | adalimumab 40 mg qow: 1.5 | adalimumab 40 mg qow:16.4 | adalimumab 40 mg qow: 26.7 | |||||
adalimumab 40 mg qow: 204 | ||||||||||
Burmester 2013 [24] | North America, Europe, Latin America, etc. | 24 | MTX (compulsory); antimalarial therapy; No other DMARDs (non-biological or biological) were permitted NSAIDs, selective cyclooxygenase-2 inhibitors, or glucocorticoids | 5, 10 mg bid | Total: 399 | Placebo: 5.4 | Placebo: 6.4 | Placebo: 1.6 | Placebo: 17.2 | Placebo: 28.2 |
Placebob: 66, 66 | tofacitinib: 5.4, 5.3 | tofacitinib: 6.5, 6.4 | tofacitinib: 1.6, 1.5 | tofacitinib: 16.2, 16.6 | tofacitinib: 28.4, 27.6 | |||||
tofacitinib: 133, 134 | ||||||||||
Van der Heijde 2013 [23] | America, Europe, Asia, Australia | 104 | MTX (compulsory); NSAIDs; corticosteroids | 5, 10 mg bid | Total: 797 | Placeboc: 5.14, 5.18 | Placeboc: 6.25, 6.29 | Placeboc: 1.4, 1.23 | Placeboc: 14.0, 14.5 | Placeboc: 23.3, 22.6 |
Placeboc: 81, 79 | tofacitinib: 5.22, 5.20 | tofacitinib: 6.34, 6.25 | tofacitinib: 1.41, 1.39 | tofacitinib: 14.1, 14.4 | tofacitinib: 24.1, 23.0 | |||||
tofacitinib: 321, 316 |
Methodological quality
Efficacy
ACR20 | ACR50 | |||
---|---|---|---|---|
Dose of tofacitinib | Sample size (tofacitinib, adalimumab) | Risk ratio [95% CI] | Sample size (tofacitinib, adalimumab) | Risk ratio [95% CI] |
Month 3
| ||||
1 mg bid | 54, 53 | 0.88 [0.52, 1.50] | 54, 53 | 0.59 [0.23, 1.51] |
3 mg bid | 51, 53 | 1.09 [0.67, 1.80] | 51, 53 | 1.25 [0.59, 2.63] |
5 mg bid | 49, 53 | 1.65 [1.08, 2.53] | 49, 53 | 1.95 [1.00, 3.80] |
10 mg bid | 61, 53 | 1.97 [1.32, 2.92] | 61, 53 | 2.35 [1.26, 4.38] |
15 mg bid | 57, 53 | 2.01 [1.35, 2.98] | 57, 53 | 2.70 [1.46, 4.98] |
Month 6,
| ||||
5 mg bid | 196, 199 | 1.09 [0.89, 1.33] | N/A | N/A |
10 mg bid | 196: 199 | 1.11 [0.91, 1.36] | N/A | N/A |
Safety
5 mg bid | 10 mg bid | |||||
---|---|---|---|---|---|---|
Adverse events | No. of studies | Sample size (tofacitinib, placebo) | Risk ratio [95% CI] | No. of studies | Sample size (tofacitinib, placebo) | Risk ratio [95% CI] |
Infection
| ||||||
Upper respiratory tract infection | 4 | 901, 522 | 1.12 [0.61, 2.05] | 4 | 896, 522 | 0.77 [0.40, 1.49] |
Urinary tract infection | 4 | 901, 522 | 1.22 [0.58, 2.57] | 4 | 901, 522 | 1.01 [0.45, 2.27] |
Bronchitis | 4 | 901, 522 | 0.80 [0.25, 2.56] | 4 | 896, 522 | 1.01 [0.34, 2.96] |
Nasopharyngitis | 5 | 928, 550 | 1.57 [0.51, 4.83] | 5 | 922,550 | 1.67 [0.82, 3.39] |
Influenza | 3 | 768, 390 | 0.37 [0.08, 1.64] | 3 | 762, 390 | 1.25 [0.25, 6.20] |
Pharyngitis | 2 | 231, 136 | 0.01 [−0.01, 0.03] | 2 | 227, 136 | 0.03 [−0.09, 0.14] |
Immune system
| ||||||
Neutropeniaa
| 4 | 826, 482 | 1.41 [0.55, 3.61] | 4 | 830, 482 | 1.73 [0.68, 4.38] |
Rash | 3 | 552, 296 | 0.32 [0.04, 2.61] | 3 | 543, 296 | 2.51 [0.63, 9.93] |
Withdrawal
|
No. of studies
|
Tofacitinib N (%)
|
Placebo N (%)
|
Risk ratio [95% CI]
| ||
All causes | 5 | 158 (12.31%) | 59 (16.71%) | 0.60 [0.45, 0.78] | ||
Adverse events | 5 | 50 (3.89%) | 8 (2.27%) | 1.43 [0.68, 3.03] | ||
Lack of efficacy | 5 | 16 (1.25%) | 20 (5.67%) | 0.18 [0.09, 0.35] |