Artikel
Tofacitinib, an Oral Janus Kinase Inhibitor, in the Treatment of Rheumatoid Arthritis: Safety and Clinical and Radiographic Efficacy in Open-Label, Long-Term Extension Studies over 7 Years
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Autoren
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Jürgen Wollenhaupt
- Schön Klinik Hamburg Eilbek, Klinik für Rheumatologie und klinische Immunologie, Hamburg
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Joel Silverfield
- Healthpoint Medical Group, Tampa, USA
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Eun Bong Lee
- Seoul National University, Seoul, South Korea
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Ketti Terry
- Pfizer Inc., Groton, USA
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Kenneth Kwok
- Pfizer Inc, New York, United States of America
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Irina Lazariciu
- Quintiles, Saint-Laurent, Canada
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Chudy Nduaka
- Pfizer Inc., Collegeville, USA
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Carol A. Connell
- Pfizer Inc., Groton, USA
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Ryan DeMasi
- Pfizer Inc., New York, USA
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Lisy Wang
- Pfizer Inc., Groton, USA
| Veröffentlicht: | 29. August 2016 |
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Gliederung
Text
Background: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We report Tofacitinib safety, tolerability, and clinical response over 84 months, and radiographic data over 12 months, in long-term extension (LTE) studies.
Methods: Data were pooled from two open-label studies (NCT00413699 [ongoing; database unlocked at March 2015 data-cut] and NCT00661661 [completed]). Pts received tofacitinib 5 or 10 mg BID as monotherapy or with background DMARDs. Primary endpoints: AEs and laboratory safety. Secondary endpoints: ACR responses, DAS28-4(ESR), HAQ-DI, and modified total Sharp score (mTSS). Safety data were included over 96 mo and efficacy data up to Mo 84 (n≤30 post-Mo 84).
Results: 4,867 pts were treated (mean [max] duration: 1,107 [2,895] days). Total tofacitinib exposure was 14,926 pt-years (py). In total, 2,132 pts (43.8%) discontinued (AEs: 1,051 [21.6%]; insufficient clinical response: 153 [3.1%]). Most common AEs: nasopharyngitis (18.1%), upper respiratory tract infection (16.2%), bronchitis (11.7%), and urinary tract infection (11.5%). Serious AEs occurred in 26.8% of pts (incidence rate [IR] 9.7/100 py [95% CI 9.2, 10.2]), and serious infection events (SIEs) in 8.4% of pts (IR 2.8/100 py [95% CI 2.5, 3.0]). Malignancies excluding NMSC were reported in 3.0% of pts (IR 1.0/100 py [95% CI 0.8, 1.1]). IRs for SIEs and malignancies through Mo 96 did not increase vs reported data through Mo 84.1 Decreased Hgb (>30% decrease from BL/Hgb <8 g/dL) occurred in 6.8% of pts. Increased aminotransferases (>3 × ULN) occurred in 5.4% (ALT) and 3.1% (AST) of pts. Moderate to severe neutropenia (absolute neutrophil count [ANC] 0.5–1.5 × 103/mm3) was noted in 1.5% of pts. Mean DAS28-4(ESR) was 6.29 at BL, 3.74 at Mo 1, and 3.20 at Mo 84. Radiographic data were available for 1,099 pts. Mean mTSS was 24.0 at BL (last index value), 25.1 at Mo 6, and 24.3 at Mo 12. Mean change from BL in mTSS was 0.3 at Mo 6 and 0.2 at Mo 12.
Conclusion: Consistent safety and sustained efficacy over 84 mo was seen in pts with RA receiving tofacitinib 5 or 10 mg BID in LTE studies. Changes in mTSS were minimal at Mo 12 in LTE studies.
