Treatment outcomes in patients with seropositive versus seronegative rheumatoid arthritis in Phase III randomised clinical trials of tofacitinib

被引：46

作者：

Bird, Paul ^{[1
]}

Hall, Stephen ^{[2
,3
]}

Nash, Peter ^{[4
]}

Connell, Carol A. ^{[5
]}

Kwok, Kenneth ^{[6
]}

Witcombe, David ^{[7
]}

Thirunavukkarasu, Krishan ^{[7
]}

机构：

[1] Univ New South Wales, Sydney, NSW, Australia

[2] Cabrini Hlth, Melbourne, Vic, Australia

[3] Monash Univ, Melbourne, Vic, Australia

[4] Univ Queensland, Brisbane, Qld, Australia

[5] Pfizer Inc, Groton, CT 06340 USA

[6] Pfizer Inc, New York, NY USA

[7] Pfizer Australia, Sydney, NSW, Australia

来源：

RMD OPEN | 2019年 / 5卷 / 01期

关键词：

CYCLIC CITRULLINATED PEPTIDE; JANUS KINASE INHIBITOR; MODIFYING ANTIRHEUMATIC DRUGS; DOUBLE-BLIND; INADEQUATE RESPONSE; JAK INHIBITOR; BACKGROUND METHOTREXATE; JAPANESE PATIENTS; OPEN-LABEL; DISEASE;

D O I：

10.1136/rmdopen-2018-000742

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Objectives Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). We examined response to tofacitinib 5 or 10 mg two times a day in patients with seropositive vs seronegative RA. Methods Data were pooled from five Phase III studies of conventional synthetic disease-modifying antirheumatic drug (csDMARD)-or biological DMARD-inadequate responders (ORAL Step [NCT00960440]; ORAL Scan [NCT00847613]; ORAL Solo [NCT00814307]; ORAL Sync [NCT00856544]; ORAL Standard [NCT00853385]). 'Serotype' subgroups were: anticyclic citrullinated peptide (CCP) and rheumatoid factor (RF) positive (anti-CCP+/RF+); anti-CCP+/RF negative (-); anti-CCP-/RF+; anti-CCP-/RF-. At month 3, ACR20/50/70 response rates, Disease Activity Score (DAS28-4[ESR])defined remission (DAS28-4[ESR]< 2.6) and low disease activity (LDA; DAS28-4[ESR]=3.2), changes from baseline (CFB) in Health Assessment Questionnaire-Disability Index (HAQ-DI), Short Form-36 Health Survey (SF-36) physical functioning and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) were evaluated. Safety endpoints were compared. Results Baseline demographics/characteristics were similar across subgroups. Tofacitinib significantly improved ACR20/50/70 response rates, DAS28-4(ESR) LDA rates and CFB in HAQ-DI and FACIT-F vs placebo across subgroups. More anti-CCP+/RF+ than anti-CCP-/ RF-patients had ACR20/50/70 responses (ACR20/50: both tofacitinib doses; ACR70: 10 mg two times a day). SF-36 physical functioning improved in anti-CCP+/ RF+, anti-CCP+/RF-and anti-CCP-/RF+ patients (both tofacitinib doses) and anti-CCP-/RF-patients (10 mg two times a day) vs placebo. More anti-CCP+/RF+ and antiCCP+/ RF-than anti-CCP-/RF-patients achieved DAS284( ESR) remission and LDA with tofacitinib 10 mg two times a day. Frequency of adverse events (AEs), serious AEs and discontinuations due to AEs were similar across subgroups. Conclusion Generally, tofacitinib efficacy (ACR20/50/70 responses) and safety were similar across subgroups. DAS28-4(ESR) remission rates and SF-36 physical functioning appeared lower in anti-CCP-patients.

引用

页数：10

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