Etanercept treatment for extended oligoarticular juvenile idiopathic arthritis, enthesitis-related arthritis, or psoriatic arthritis: 6-year efficacy and safety data from an open-label trial

Abstract

Background To describe the 6-year safety and efficacy of etanercept (ETN) in children with extended oligoarticular juvenile idiopathic arthritis (eoJIA), enthesitis-related arthritis (ERA), and psoriatic arthritis (PsA) Methods Patients who completed the 2-year, open-label, phase III CL inical Study I n P ediatric P atients of E tanercept for Treatment of E R A, PsA, and Extended Oligoarthritis (CLIPPER) were allowed to enroll in its 8-year long-term extension (CLIPPER2). Children received ETN at a once-weekly dose of 0.8 mg/kg, up to a maximum dose of 50 mg/week. Efficacy assessments included the JIA core set of outcomes, the JIA American College of Rheumatology response criteria (JIA-ACR), and the Juvenile Arthritis Disease Activity Score (JADAS). Efficacy data are reported as responder analyses using a hybrid method for missing data imputation and as observed cases. Safety assessments included treatment-emergent adverse events (TEAEs). Results Out of 127 patients originally enrolled in CLIPPER, 109 (86%) entered CLIPPER2. After 6 years of trial participation (2 years in CLIPPER and 4 years in CLIPPER2), 41 (32%) patients were still taking ETN, 13 (11%) entered the treatment withdrawal phase after achieving low/inactive disease (of whom 7 had to restart ETN), 36 (28%) discontinued treatment for other reasons but are still being observed, and 37 (29%) discontinued treatment permanently. According to the hybrid imputation analysis, proportions of patients achieving JIA ACR90, JIA ACR100, and JADAS inactive disease after the initial 2 years of treatment were 58%, 48%, and 32%, respectively. After the additional 4 years, those proportions in patients who remained in the trial were 46%, 35%, and 24%. Most frequently reported TEAEs [ n (%), events per 100 patient-years] were headache [28 (22%), 5.3], arthralgia [24 (19%), 4.6], and pyrexia [20 (16%), 3.8]. Number and frequency of TEAEs, excluding infections and injection site reactions, decreased over the 6-year period from 193 and 173.8, respectively, during year 1 to 37 and 61.3 during year 6. A single case of malignancy (Hodgkin’s lymphoma) and no cases of active tuberculosis, demyelinating disorders, or deaths were reported. Conclusions Open-label etanercept treatment for up to 6 years was safe, well tolerated, and effective in patients with eoJIA, ERA, and PsA. Trial registration ClinicalTrials.gov: CLIPPER, NCT00962741 , registered 20 August, 2009, CLIPPER2, NCT01421069 , registered 22 August, 2011. Electronic supplementary material The online version of this article (10.1186/s13075-019-1916-9) contains supplementary material, which is available to authorized users...

Long-term safety and effectiveness of etanercept in JIA: an 18-year experience from the BIKER registry

“…Our analysis included data from 72 patients who completed the ninth year of continuous etanercept treatment. The improvement in disease activity reached in the rst year showed to be maintained during up to nine years of sustained drug use, in accordance to observations from previous studies [22][23]. One third of the patients who had discontinued etanercept treatment due to remission remained in clinical remission off-biologics one year after etanercept withdrawal.…”

“…While other groups have also found higher serious infection rates upon etanercept [3,23] [25]. In our study, herpes zoster reactivation was the only opportunistic infection reported, and it was more often observed in etanercept than in biologic-naïve patients with methotrexate, similarly to what described by others [22][23].…”

“…The comedication with methotrexate, documented in two thirds of the etanercept cohort, may be also a contributing factor, as it was showed in prior studies that serious infections had a higher incidence in patients treated with etanercept-methotrexate combination treatment compared to monotherapy [3]. The rates for serious infections in the etanercept cohort from the BiKeR registry were similar to those reported in other long-term registry studies [19,20], but lower than what described in longterm controlled clinical trials [18,22]. While other groups have also found higher serious infection rates upon etanercept [3,23] [25].…”

Long-term safety and effectiveness of etanercept in JIA: an 18-year experience from the BIKER registry

“…While other groups have also found higher serious infection rates upon etanercept [3,24] [25]. In our study, herpes zoster reactivation was the only opportunistic infection reported, and it was more often observed in etanercept than in biologic-naïve patients with methotrexate, similarly to what described by others [23][24].…”

“…The comedication with methotrexate, documented in two thirds of the etanercept cohort, may be also a contributing factor, as it was showed in prior studies that serious infections had a higher incidence in patients treated with etanercept-methotrexate combination treatment compared to monotherapy [3]. The rates for serious infections in the etanercept cohort from the BiKeR registry were similar to those reported in other long-term registry studies [19][20], but lower than what described in long-term controlled clinical trials [18,23]. While other groups have also found higher serious infection rates upon etanercept [3,24] [25].…”