Original articleSafety of intra-articular injection of etanercept in small-joint arthritis: an uncontrolled, pilot-study with independent imaging assessment
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.
References (20)
- et al.
Localization of tumor necrosis factor receptors in the synovial tissue and cartilage–pannus junction in patients with rheumatoid arthritis. Implications for local actions of tumor necrosis factor alpha
Arthritis Rheum.
(1992) - et al.
Disease severity in rheumatoid arthritis: relationships of plasma tumor necrosis factor-alpha, soluble interleukin 2-receptor, soluble CD4/CD8 ratio, neopterin, and fibrin D-dimer to traditional severity and functional measures
J. Clin. Immunol.
(1992) Hydrocortisone and cortisone injection into arthritic joints. Comparative effects of and use of hydrocortisone as a local antiarthritic agent
JAMA
(1951)- et al.
Treatment of refractory inflammatory monoarthritis in ankylosing spondylitis by intraarticular injection of infliximab
J. Rheumatol.
(2006) - Kellner H, Kroetz M, Schattenkirchner M, Kellner W. Successful therapy of sacroiliitis in AS patients be intraarticular...
- et al.
Local infusion of infliximab for the treatment of acute joint inflammation
Ann. Rheum. Dis.
(2003) - et al.
Treatment of resistant rheumatoid arthritis by intra-articular infliximab injections: a pilot study
Ann. Rheum. Dis.
(2004) - et al.
Acute injection site reaction to intraarticular etanercept administration
Arthritis Rheum.
(2003) - et al.
Importance of placement of intra-articular steroid injections
BMJ
(1993) - et al.
Use of small amounts of ultrasound guided air for injections
Ann. Rheum. Dis.
(2000)