Safety and Effectiveness of Peficitinib (ASP015K) in Patients with Rheumatoid Arthritis: Final Results (32 Months of Mean Peficitinib Treatment) From a Long-Term, Open-Label Extension Study in Japan, Korea, and Taiwan

Abstract

Introduction: This final analysis of a long-term extension (LTE) study assessed the safety, tolerability, and effectiveness of peficitinib (ASP015K), a pan-Janus kinase inhibitor, in Asian patients with rheumatoid arthritis (RA).

Methods: Patients had previously completed the 12-week phase 2b (RAJ1), or 52-week phase 3 (RAJ3 and RAJ4) peficitinib studies in Japan, Korea, and Taiwan, and received oral peficitinib 50 or 100 mg/day. Dose increase to 150 mg/day or reduction to 50 mg/day was permitted. Efficacy endpoints included American College of Rheumatology (ACR)20/50/70 response rates, 28-joint Disease Activity Score with C-reactive protein (DAS28-CRP), and ACR components. Safety endpoints included treatment-emergent adverse events (TEAEs), and incidence rates (IRs) of adverse events of special interest per 100 patient-years (PY).

Results: Overall, 843 patients received peficitinib for a mean 32.0 months (maximum 85.2 months), and most (64.4%) received peficitinib 100 mg/day as a maximum dose. Respective ACR20/50/70 response rates were maintained from baseline (week 0 of LTE; 71.6, 52.1, and 34.7%) to end of treatment (78.7, 63.3, and 44.1%); continuous improvements in ACR components and DAS28-CRP were observed from the baselines of preceding studies and throughout the LTE. Overall, 796/843 (94.4%) patients experienced TEAEs; most were severity grade 1/2. Most common TEAEs were nasopharyngitis (47.0%) and herpes zoster (17.3%). Drug-related TEAEs leading to permanent discontinuation occurred in 140 (16.6%) patients, and IRs (95% confidence interval) per 100 PY of serious infections, herpes zoster-related disease, and malignancies were 2.7 (2.1, 3.4), 7.3 (6.2, 8.6), and 1.2 (0.9, 1.8), respectively. Two deaths occurred during the study; one each from diffuse large B cell lymphoma and pneumonia, which were, respectively considered probably and possibly related to study drug.

Conclusions: Improvements in effectiveness variables were maintained during this long-term study of peficitinib in Asian patients with RA; peficitinib was generally well tolerated over a mean 32 months' duration.

Trial registration: ClinicalTrials.gov. NCT01638013, retrospectively registered on 11 July 2012 https://ichgcp.net/clinical-trials-registry/NCT01638013 .

Keywords: Herpes zoster; Janus kinase inhibitors; Long-term extension study; Peficitinib; Rheumatoid arthritis; Serious infection; Targeted synthetic DMARDs.

Figures

Fig. 1

Patient flow through the long-term extension study. *Discontinued during overall period: discontinued at any time from start of initial dosing of study drug through the last dose day in the overall period

Fig. 2

Response rates for ACR20, ACR50, and ACR70 over time (FAS). *Includes LOCF. ACR American College of Rheumatology, EOT end of treatment, FAS full analysis set, LOCF last observation carried forward

Fig. 3

ACR20 response at each visit by maximum peficitinib dose level (FAS). *Includes LOCF. ACR American College of Rheumatology, EOT end of treatment, FAS full analysis set, LOCF last observation carried forward

Fig. 4

Mean changes from baseline over time in a DAS28-CRP, b CDAI, and c SDAI scores (FAS). *Includes LOCF. CDAI Clinical Disease Activity Index, DAS28-CRP Disease Activity Score in 28 joints based on C-reactive protein, EOT end of treatment, FAS full analysis set, LOCF last observation carried forward, SDAI Simplified Disease Activity Index

Fig. 5

The proportion of patients achieving remission/LDA in relation to a DAS28-CRP < 2.6, b DAS28-CRP ≤ 3.2, c CDAI ≤ 2.8, d SDAI ≤ 3.3, and e ACR/EULAR Boolean-based definition of remission (FAS). *Includes LOCF. ACR American College of Rheumatology, CDAI Clinical Disease Activity Index, DAS28-CRP Disease Activity Score in 28 joints based on C-reactive protein, EOT end of treatment, EULAR European League Against Rheumatism, FAS full analysis set, LDA low disease activity, LOCF last observation carried forward, SDAI Simplified Disease Activity Index

Fig. 6

Incidence of adverse events of special interest per 100 PY during the overall period for a serious infections, b herpes zoster-related disease, and c malignancies (SAF). PY were calculated from initial dose up to first incidence of the event for patients who had ≥ 1 event, and from initial dose through follow-up for patients who had no events; incidence rate was calculated as (100 × number of patients who had ≥ 1 incidence)/total PY. CI confidence interval, IR incidence rate, PY patient-years, SAF safety analysis set

Fig. 7

Incidence of treatment-emergent adverse events of special interest per 100 PY during the overall period (SAF). PY were calculated from initial dose up to first incidence of the event for patients who had ≥ 1 event, and from initial dose through follow-up for patients who had no events; incidence rate was calculated as (100 × number of patients who had ≥ 1 incidence)/total PY. CI confidence interval, IR incidence rate, PY patient-years, SAF safety analysis set