Canakinumab in the Treatment of Erosive Hand Osteoarthritis: A Case Series

Abstract

Background: Erosive hand Osteoarthritis (EOA) is a common and debilitating form of hand OA for which there are no proven or efficacious therapies. Interleukin-1 beta (IL-1β) plays a prominent role in OA joint inflammation. Canakinumab is a selective IL-1β inhibitor. The author hypothesized that canakinumab would be effective in alleviating the symptoms and functional limitations of EOA. Erosive hand Osteoarthritis (EOA) is a subtype of osteoarthritis (OA) which manifests as pain, swelling, redness, and warmth and is associated with radiographic changes such as central collapsing erosions and gull wing deformity. EOA eventually leads to joint deformity and ankylosis. Despite greater analgesic use, patients with EOA have worse functional outcome and more pain than those with controlled inflammatory arthritis such as Rheumatoid Arthritis or Psoriatic Arthritis [1]. Pain scores remained significantly higher in patients with erosive OA after Compared to OA of the hands, EOA “is an important cause of disability, usually compared to the handicap caused by Rheumatoid Arthritis” [2]. The proinflammatory cytokines interleukin-1 beta (IL1β) and to a lesser extent tumor necrosis factor alpha (TNF-α) play a key role in the destruction of the cartilage matrix in OA [3]. In the current medical literature the use of disease modifying agents such as hydroxychloroquine in patients with EOA is based on a small retrospective study of 8 patients reported in the mid-1990s [4]. No other literature exists to support use of other disease modifying anti-rheumatic drugs (DMARDs) such as methotrexate or leflunomide presumably due to the higher risk of toxicity with these agents. A small trial of 14 patients treated with the peroxisome proliferator-activated receptor alpha agonist fenofibrate experienced significant decreases in pain score, tender joint count, duration of morning stiffness, disease activity score, Cochin index, and Erythrocyte Sedimentation Rate (ESR) [5]. An open label trial of adalimumab administered every other week treating 12 patients for 12 weeks demonstrated only a statistically significant improvement in swollen joint counts but not in other outcome measures such as pain or disability [6]. A small (3 patient) case series retrospectively reporting improvement of EOA symptoms with use of anakinra (Kineret®) reported encouraging results after 3 months of treatment [2]. Methods: This prospective case series enrolled 3 patients with EOA who were treated with canakinumab 160 mg subcutaneously once. They were followed over a 12 week period, with visits at week 4, week 8, and week 12. It was anticipated that the effect of canakinumab would wear off and pain/function would return to baseline at week 12. The primary outcome of the study was improvement in QuickDASH at week 8. Secondary outcomes included changes in Health Assessment-Disability Index, subject reported pain, grip strength, and shirt button time. Subjects also had swollen and tender joint counts recorded. Erythrocyte Sedimentation Rate and C-Reactive Protein were measured. Results: No clinical or statistically significant improvement in QuickDASH, the primary study outcome, was noted. A minor trend in improvement was noted in shirt button time, but this improvement was not statistically significant. All other outcomes did not demonstrate any clinically or statistically significant trends. Conclusion: No clinical improvements in the various functional and clinical parameters studied were noted. The lack of effect of canakinumab and the small size of the trial should not dissuade future research.