Intra-articular etanercept treatment for severe diffuse pigmented villonodular knee synovitis

Abstract

Pigmented villonodular synovitis (PVNS) is a rare pre-malignant disease that require aggressive treatment as surgical synovectomy, eventually followed by radiosynovectomy. Nevertheless, the disease often reoccurs after these treatments. To determine the safety and efficacy of intra-articular (IA) TNF-a blockade with etanercept (ETN), before extended arthroscopic synovectomy, in severe PVNS of the knee, two patients, (a 26-year-old man with B27+ undifferentiated spondylarthropathy and a 32-year-old femal with seronegative olygoarthritis), affected by diffuse knee PVNS (diagnosis made by histological examination), resistant to IA corticosteroid injections and to repeated arthroscopic synovectomy, were submitted, after protocol approval by human research committee and patient’s written informed consent to intra-articular etanercept (IA-ETN) treatment with a different dosage schedule: 12.5 mg weekly IA-ETN injection for 4 weeks, followed by extended arthroscopic synovectomy and of 25 mg IA-ETN injection for 4 weeks, respectively. Previous DMARDs treatment was continued in stable appropriate doses. Any adverse events were recorded throughout the study. The following parameters were considered as clinical endpoints: 1) Knee Joint Index (KJI: range 0-14); 2) Thompson index (THI: range 0-9) At the study entry and at the end of follow-up, high frequency ultrasound grey scale synovial thickening (US-ST) was also assessed. No adverse events were observed due to IA-ETN and to arthroscopic synovectomy. Marked improvement of knee disease activity over time and sustained functional recover was obtained. US-ST evaluation before treatment initiation and at the end of follow-up confirmed the regression of knee joint synovial proliferatio

Pigmented Villonodular Synovitis for Combined Therapy

“…Recent studies showed that anti-inflammatory therapy with anti-TNF biologics (infliximab systemic and etanercept intra-articular) and anticancer imatinib (tyrosine-kinase inhibitor of signaling cascade) may be helpful in management of PVNS [10,13,14]. Large amounts of TNF-alpha were found in PVNS similarly to rheumatoid arthritis (RA).…”

“…Synovial hyperplasia in PVNS might be due to upregulation of synoviocyte proliferation as represented by activation of telomerase, which is evident in the majority of tumor cell lines [15]. That is why the treatment such as with TNF-alpha blockade did not reduce synovial tumor mass as measured by MRI but alleviated and stabilized synovial inflammation and joint effusion [13,14]. However, treatment with imatinib showed MRI decrease in size of lesions in 50% of patients.…”

Pigmented Villonodular Synovitis: Current Concepts About Diagnosis and Management

“…In addition, a marked reduction in macrophages and TNF-a expression in the synovium was found. Fiocco et al reported two patients with recurrent disease of the knee who benefited from the TNF-a blocker etanercept [63]. Knee function and disease activity improved, which was confirmed by regression of knee joint synovial proliferation.…”

“…Some research uses anti-TNF-a as a local or general treatment in patients with relapsing PVNS, with relatively good results [30,63,64]. Kroot reported a patient with recurrent PVNS of the knee, which clinically improved after TNF-a blockade [30].…”

Is intra-articular infliximab therapy a good alternative to radionuclide synovectomy for a patient with refractory pigmented villonodular synovitis?

“…Fiocco at al. [14] described 2 patients with recurrent PVNS, successfully treated with intra-articular etanercept injections. The patients regained full range of mo-Reumatologia 2021; 59/5 tion in the treated joints, and US evaluation revealed reduction of thickness of the synovial tissue.…”