Publications

乾癬性関節炎におけるトファシチニブの安全性を、Phase IIIと長 期試験における統合解析と実臨床観察データを比較

Drug Saf. 2020;43:379-392

Burmester GR,

Curtis JR,

Yun H,

FitzGerald O,

Winthrop KL,

Azevedo VF,

Rigby WFC,

Kanik KS,

Wang C,

Biswas P,

Jones T,

Palmetto N,

Hendrikx T,

Menon S,

Rojo R

Patients with psoriatic arthritis (PsA) had similar safety profile with TOF to that of other systemic therapies in real-world settings, except for the known risk of HZ. Treatment recommendations from EULAR and GRAPPA for patients with PsA vary according to adverse prognostic risk factors, disease manifestations and responsiveness to prior treatment. Safety concerns for most PsA therapies include gastrointestinal AEs, hepatotoxicity, opportunistic infections (OIs) including TB, and SIEs. This stu...

Keywords:

• JAK,
• Tofacitinib,
• Phase 3,
• Real-World

中等度から重度の関節リウマチにおけるPeficitinibの2年の 安全性と有効性: フェーズ IIb, オープンラベル延長試験

Rheumatol Ther . 2019 Dec;6(4):503-520. doi: 10.1007/s40744-019-00167-6. Epub 2019 Aug 13.

Genovese MC,

Greenwald MW,

Gutierrez-Ureña SR

Peficitinib (PEF) 100 mg QD demonstrated a stable safety profile and sustained effectiveness in patients with moderate-to-severe RA in a two-year extension of two global phase IIb studies. Patients enrolled in the LTE had completed one of two 12-week phase IIb PEF trials, one with MTX and one without. The primary objective of the LTE was to assess treatment-emergent adverse events and clinical laboratory evaluations for 105 weeks. As a secondary objective, an additional 2-years of effectiveness ...

Keywords:

• JAK,
• Peficitinib,
• Phase 2,
• LTE

東アジアの中等症から重症の活動性関節リウマチ患者にお けるBaricitinibの安全性: 臨床試験からの統合解析

Int J Rheum Dis . 2020 Jan;23(1):65-73. doi: 10.1111/1756-185X.13748.

Chen YC,

Yoo DH,

Lee CK

Post-hoc analyses of five completed phase II and III trials and an ongoing LTE suggested that BARI QD is well tolerated in East Asian patients with moderate-to-severe RA, with a similar safety and tolerability profile to the overall population.The majority of clinical evidence for RA treatments has been obtained from a predominantly Caucasian population, which may not be relevant to East Asian patients. In this post-hoc safety analysis, 740 Japanese, Taiwanese, Korean and Chinese patients were i...

Keywords:

• JAK,
• Baricitinib,
• Safety,
• Meta analysis

フェーズ2と3試験におけるウパダシチニブの曝露と反応性に 関する有効性安全性解析 関節リウマチにおけるベネフィットリスク

Clin Pharmacol Ther . 2020 Apr;107(4):994-1003. doi: 10.1002/cpt.1671.

Nader A,

Mohamed M-EF,

Winzenborg I,

Doelger E,

Noertersheuser P,

Pangan AL,

Othman AA

UPA 15 mg provided the optimal benefit-risk in RA through maximizing efficacy with only small incremental benefit with 30 mg, and with consistency across RA subpopulations and with UPA monotherapy or combination with csDMARDs. Exposure-response analyses were conducted using combined data from two Phase 2b and five Phase 3 studies in order to characterise the relationship between plasma exposure and efficacy, as well as to select safety parameters using the totality of the data in subjects with R...

Keywords:

• JAK,
• Upadacitinib,
• Efficacy,
• Safety

関節リウマチにおける低分子JAK阻害薬の感染リスクに関す るシステマティックレビューとメタ解析

Rheumatology (Oxford) 2019;58(10):1755–66

Bechman K,

Subesinghe S,

Norton S,

Atzeni F,

Galli M,

Cope AP,

Winthrop KL,

Galloway JB

Absolute serious infection rates were low. However, across the JAKinibs, the incidence of HZ is higher than expected for the population. While the risk was numerically greatest with BARI, indirect comparisons between the drugs did not demonstrate any significant difference in risk. How JAKinibs increase the risk of HZ reactivation is unclear, but how different JAKs interact in the immune response suggest that there may be differences in safety profiles between JAKinib drugs, underpinned by their...

Keywords:

• Safety,
• Review

抗リウマチ薬に抵抗性の中等度から重度関節リウマチ患者に おける臨床的反応性に対する Filgotinib の Placebo対照とした 効果 : FINCH 2 無作為化試験

JAMA 2019 322(4):315-325

Genovese MC,

Kalunian K,

Gottenberg JE,

Mozaffarian N,

Bartok B,

Matzkies F,

Gao J,

Guo Y,

Tasset C,

Sundy JS,

de Vlam K,

Walker D,

Takeuchi T

Among RA patients with an inadequate response or intolerance to bDMARDs, filgotinib (FIL) doses, compared to PBO resulted in significantly greater proportions achieving a clinical response at Wk12.Patients with active RA despite treatment with bDMARD therapy need treatment options. The FINCH 2 Phase 3 study compared the effects of FIL vs PBO for the treatment of RA patients with inadequate response or intolerance to ≥1 prior bDMARDs. Patients were randomized in a 1:1:1 ratio, receiving FIL 200 m...

Keywords:

• JAK,
• Filgotinib,
• Phase 3

反応性不良または試験デザインのためアダリムマブからバリシチニブにスイッチした患者の臨床的アウトカム: RA患者を対象とした第３相試験

Ann Rheum Dis. 2019 Jul;78(7):890-898.

Tanaka Y,

Fautrel B,

Keystone EC,

Ortmann RA,

Xie L,

Zhu B,

Issa M,

Patel H,

Gaich CL,

de Bono S,

Rooney TP,

Taylor PC

Switching from ADA to BARI without a lengthy washout period can be executed with acceptable safety and tolerability and was associated with maintained disease control. Switching therapies in RA is commonplace in myriad scenarios including inadequate responses, intolerances and patient preference. Assessing the safety and efficacy of new treatments such as BARI, in the context of use as a replacement therapy, is beneficial. A previous study (RA-BEACON) has demonstrated that safely switching from ...

Keywords:

• JAK,
• Baricitinib,
• Phase 3

関節リウマチにおける低分子JAK阻害薬の感染リスクに関す るシステマティックレビューとメタ解析

Rheumatology (Oxford). DOI: 10.1093/rheumatology/kez087

Bechman K,

Subesinghe S,

Norton S,

Atzeni F,

Galli M,

Cope AP,

Winthrop KL,

Galloway JB

How JAKinibs increase the risk of HZ reactivation is unclear. Roles of different JAKs in the immune response may suggest differences in safety profiles between drugs, underpinned by their differential JAK selectivity profiles. The authors undertook a systematic review and meta-analysis to evaluate SI and opportunistic indicator infections including HZ in RA Phase II/III clinic trials with JAKinibs. A literature review of RCT of TOF (5 mg BID), BARI (4 mg OD) and UPA (15 mg OD) was conducted. A p...

Keywords:

• JAK,
• Safety,
• Meta analysis,
• Infections

トファシチニブ治療関節リウマチ患者における 結核, B型肝炎および帯状疱疹

Immunotherapy. 2019 Mar;11(4):321-333.

Zhang Z,

Deng W,

Wu Q,

Sun L

The risk of TB and hepatitis B virus (HBV) appears to be no greater with TOF than with bDMARDs. Most cases of TB during TOF studies occurred in regions with high background rate of TB, including east Asian countries. TOF is also associated with a higher rate of herpes zoster (HZ) compared with bDMARDs. DMARDs used to treat RA can increase the risk of infections by causing a degree of immunosuppression. A range of bacterial and viral infections have been observed in association with DMARD therapy...

Keywords:

• JAK,
• Tofacitinib,
• Infections

日本人活動性関節リウマチ患者におけるバリシチニブの中央値1.6年の治療期間における安全性評価: フェーズ2および3治験の統合解析

Mod Rheumatol. 2019 Feb 20:1-23. DOI: 10.1080/14397595.2019.1583711

Harigai M,

Takeuchi T,

Smolen JS,

Winthrop KL,

Nishikawa A,

Rooney TP,

Saifan CG,

Issa M,

Isaka Y,

Akashi N,

Ishii T,

Tanaka Y

In this integrated analysis, BARI showed an acceptable safety profile in Japanese patients with up to 3.2 years of exposure. Other than incidences of herpes zoster (HZ), no major differences were noted with BARI safety in Japanese patients with RA, compared to the patients in the integrated database.BARI has previously demonstrated significant clinical efficacy and acceptable safety. Japanese patients who participated in the BARI clinical development programme, were comparable to those from the ...

Keywords:

• JAK,
• Baricitinib,
• Safety,
• Phase 3