Two-Year Safety and Effectiveness of Peficitinib in Moderate-To-Severe Rheumatoid Arthritis: A Phase IIb, Open-Label Extension Study

Abstract

Introduction: Peficitinib is a novel orally bioavailable, once-daily Janus kinase (JAK) inhibitor approved in Japan for the treatment of rheumatoid arthritis (RA). This 2-year extension study of two global phase IIb trials investigated the long-term safety and effectiveness of peficitinib.

Methods: All eligible patients with moderate-to-severe RA including patients in the placebo group who participated in one of two global phase IIb trials ('with methotrexate' or 'without methotrexate') were included in this 2-year open-label extension study and were converted to peficitinib 100 mg once daily. The primary objective was to evaluate an additional 2 years of safety by assessing treatment-emergent adverse events (AEs) and clinical laboratory evaluations for 105 weeks. Evaluation of an additional 2 years of effectiveness using American College of Rheumatology (ACR) 20/50/70 responses was the exploratory objective.

Results: Overall, 611 patients were enrolled in the extension study: 319 (52.2%) patients completed the study and 292 (48%) discontinued treatment, including for withdrawal of patient consent (n = 96), failure to achieve low disease activity (n = 62), and AE not including death (n = 41). AEs were reported in 463 (76%) patients. The most common AEs (per 100 patient-years) were upper respiratory tract infections (9.9) and urinary tract infections (7.2). Serious AEs were reported in 80 (13%) patients, with incidences per 100 patient-years of serious infections 2.7, herpes zoster 1.5 (including one herpes zoster ophthalmic), and malignancies 0.6 (most frequently basal cell carcinoma). At week 105, 269 (44%) patients demonstrated an ACR20 response relative to their respective phase IIb trial baselines.

Conclusion: Among 319 patients who completed this 2-year extension of two global phase IIb studies, peficitinib 100 mg once daily demonstrated a stable safety profile and sustained effectiveness in patients with moderate-to-severe RA.

Trial registration: ClinicalTrials.gov identifier, NCT01711814. Registered 19 October 2012.

Funding: Astellas Pharma Global Development, Inc.

Keywords: Janus kinase (JAK) inhibitor; Long-term extension; Peficitinib; Rheumatoid arthritis.

Figures

Fig. 1

Disposition of patients. *‘Discontinued treatment’ refers to any patient who discontinued at any time between receiving their first and last dose of peficitinib 100 mg. †Patients had not achieved either low disease activity or remission by their most recent visit, as determined by DAS28(CRP) < 3.2, DAS28(ESR) < 3.2 or SDAI ≤ 11 (if CRP was available) or CDAI ≤ 10 (if CRP was not available). Patients also met the discontinuation criteria if, after achieving low disease activity or remission, they experienced moderate or high disease activity for two consecutive visits as determined by DAS28(CRP) ≥ 3.2 (if CRP was available), DAS28(ESR) ≥ 3.2 (if ESR was available), and SDAI > 11 (if CRP was available) or CDAI > 10 (if CRP was not available). ‡Two patients discontinued treatment because of ‘miscellaneous’ reasons (one patient in the peficitinib 50 mg/100 mg group because of entering the study in error and one patient in the peficitinib 150 mg/100 mg group because of moving further from the study site). ACR20 American College of Rheumatology 20% improvement criteria, CDAI Clinical Disease Activity Index, CRP C-reactive protein, DAS28 Disease Activity Score in 28 joints, ESR erythrocyte sedimentation rate, LTE long-term extension, SDAI Simplified Disease Activity Index

Fig. 2

a ACR20/50/70 responses, b maintenance of ACR20 responses, and c DAS28(CRP) and DAS28(ESR) over time. All data are relative to phase II trial baselines and were analysed using observed data. a ACR20/50/70 responses [percentages are calculated based on total number of patients in the FAS (N = 611)]. b Maintenance of ACR20 responses in patients who achieved an ACR20 response in their previous respective phase II trial. c Mean (± standard deviation) change from baseline DAS28(CRP) and DAS28(ESR). ACR20 American College of Rheumatology criteria for 20% improvement, ACR50 ACR 50% response, ACR70 ACR 70% response, BL baseline, DAS28(CRP) disease activity score in 28 joints using C-reactive protein DAS28(ESR) disease activity score in 28 joints using erythrocyte sedimentation rate