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A phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib ( CP-690,550 ) versus placebo in combination with background methotrexate in patients with active rheumatoid arthritis and an inadequate response to methotrexate alone . OBJECTIVE To compare the efficacy , safety , and tolerability of 6 dosages of oral tofacitinib ( CP-690,550 ) with placebo for the treatment of active rheumatoid arthritis ( RA ) in patients receiving a stable background regimen of methotrexate ( MTX ) who have an inadequate response to MTX monotherapy . METHODS In this 24-week , double-blind , phase IIb study , patients with active RA ( n = 507 ) were randomized to receive placebo or tofacitinib ( 20 mg/day , 1 mg twice daily , 3 mg twice daily , 5 mg twice daily , 10 mg twice daily , or 15 mg twice daily ) . All patients continued to receive a stable dosage of MTX . The primary end point was the American College of Rheumatology 20 % improvement criteria ( ACR20 ) response rate at week 12 . RESULTS At week 12 , ACR20 response rates for patients receiving all tofacitinib dosages ≥3 mg twice daily ( 52.9 % for 3 mg twice daily , 50.7 % for 5 mg twice daily , 58.1 % for 10 mg twice daily , 56.0 % for 15 mg twice daily , and 53.8 % for 20 mg/day ) were significantly ( P ≤ 0.05 ) greater than those for placebo ( 33.3 % ) . Improvements were sustained at week 24 for the ACR20 , ACR50 , and ACR70 responses , scores for the Health Assessment Questionnaire disability index , the 3-variable Disease Activity Score in 28 joints using the C-reactive protein level ( DAS28-CRP ) , and a 3-variable DAS28-CRP of < 2.6 . The most common treatment-emergent adverse events occurring in > 10 % of patients in any tofacitinib group were diarrhea , upper respiratory tract infection , and headache ; 21 patients ( 4.1 % ) experienced serious adverse events . Sporadic increases in transaminase levels , increases in cholesterol and serum creatinine levels , and decreases in neutrophil and hemoglobin levels were observed . CONCLUSION In patients with active RA in whom the response to MTX has been inadequate , the addition of tofacitinib at a dosage ≥3 mg twice daily showed sustained efficacy and a manageable safety profile over 24 weeks .
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Intervention_Pharmacological
oral JAK inhibitor tofacitinib ( CP-690,550 )
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Intervention_Control
placebo
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Intervention_Pharmacological
background methotrexate
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Intervention_Pharmacological
methotrexate alone
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Intervention_Pharmacological
oral tofacitinib ( CP-690,550 )
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Intervention_Control
placebo
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Intervention_Pharmacological
methotrexate ( MTX )
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Intervention_Pharmacological
MTX monotherapy
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Intervention_Control
placebo
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Intervention_Pharmacological
tofacitinib
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Intervention_Pharmacological
MTX
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Intervention_Pharmacological
tofacitinib
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Outcome_Other
efficacy , safety , and tolerability
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Outcome_Physical
American College of Rheumatology 20 % improvement criteria ( ACR20 ) response rate
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Outcome_Physical
ACR20