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

Abstract

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]). a € 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 anti-CCP+/RF- than anti-CCP-/RF- patients achieved DAS28-4(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.