Elsevier

Joint Bone Spine

Volume 73, Issue 6, December 2006, Pages 714-717
Joint Bone Spine

Original article
Safety of intra-articular injection of etanercept in small-joint arthritis: an uncontrolled, pilot-study with independent imaging assessment

https://doi.org/10.1016/j.jbspin.2006.05.004Get rights and content

Abstract

This study was conducted to test the safety of intra-articular tumor necrosis factor alpha (TNF-α) antagonists in small joints with arthritis. A dose of 2–8 mg etanercept was given intra-articularly guided by ultrasonography (US) in 26 patients with a flare of arthritis in a particular joint (16 wrists, two elbows, two ankles, six finger joints). Primary end points were imaging analyses by independent investigators: US-Doppler measurements were performed in all patients before and after the injection and MRI before and after were obtained in nine patients. The only adverse event was a case of swelling of the hand lasting 2 days after a wrist injection. Two patients had a supplementary glucocorticoid injection and were excluded from efficacy analysis after 4 days and 3 weeks, respectively. VAS for pain decreased after 1 week in 23 of 25 patients (median 0.62), and after 1 month in 14 of 24 patients (median 0.60). No significant changes were seen in erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP). On MRI, all nine cases tested had a reduction in synovial thickness (P = 0.008) and US Doppler signals diminished after treatment (resistance index (RI) P = 0.02, pixels P = 0.09). In conclusion, intra-articular injection of etanercept gave no noticeable adverse events.

Introduction

Tumor necrosis factor alpha (TNF-α) is found in the synovial tissue and cartilage–pannus junctions in patients with rheumatoid arthritis (RA) [1] and has been associated with levels of pain [2]. In arthritis, systemic anti-TNF-α therapy is seemingly as effective as glucocorticoids and might also be used for injections into joint in parallel to the widespread use of intra-articular injections of corticosteroids [3]. Circumstances warranting the more expensive biological medication would include former adverse events to the corticosteroids or a reduction in steroidal load to the individual patient. The few studies published on anti-TNF medications given intra-articularly have varying results [4], [5], [6], [7], [8]. Some of this variation may be due to extra-articular placement of the injections [9], which can be avoided by giving the injection guided by ultrasound [10].

The aim of this study was to test the safety of TNF-α antagonists by etanercept (Enbrel®) administered intra-articularly in patients with a flare of RA in single joints. The treatment was restricted to small joints in which a limited dose was expected to have a local impact on the arthritis.

Section snippets

Patients

Patients aged over 18 years with RA were recruited from the outpatient clinic at the Department of Rheumatology, Frederiksberg Hospital, Denmark. Patients were eligible irrespective of DMARD treatment; however, none received anti-TNF-α therapy. Intra-articular therapy was indicated because of flare of arthritis activity in single joint(s). Patients were excluded if they had received intra-articular injection of steroids in the joint in the preceding 3 months, or had an increased risk of

Safety

Only one participant reported an adverse event during the study. This participant had received etanercept 4 mg in the wrist and developed a slight, diffuse swelling on the back of the hand the day after the aspiration/injection. No redness or induration of the tissue was present and the swelling subsided 2 days later. This participant responded well to therapy and had no other noticeable effects. The remaining participants had no adverse events, apart from temporary local soreness. No symptom

Discussion

Experience with intra-articular administration of etanercept is limited. In the present study, 25 of the 26 participants were treated without any adverse events that could be ascribed to the injected etanercept, while one participant had local swelling of the hand for 2 days. The safety of etanercept in the joint was a major concern as subcutaneous administration of etanercept may induce a local reaction [15]. Also, a local reaction has been speculated in one case of inflammatory reaction in a

Acknowledgements

We would like to thank study nurse Merete Wille, secretary Mette Gad, and the laboratory technicians Inger Wätjen and Tove Riis Johannessen for skilled assistance. This study was supported by grants from the Oak Foundation.

Conflicting interests

Henning Bliddal has received a grant from Wyeth Pharmaceuticals, which supported this study economically and donated the etanercept. None of the authors is employed by or receives salary from any company.

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