Abstract
IntroductionInflammation associated with synovial expression of TNFα is a recognised feature of osteoarthritis (OA), although no studies have yet reported beneficial effects of anti-TNFα therapy on clinical manifestations of inflammation in OA.MethodsWe conducted an open-label evaluation of adalimumab over 12 weeks in 20 patients with OA of the knee and evidence of effusion clinically. Inclusion criteria included daily knee pain for the month preceding study enrolment and a summed pain score of 125 to 400 mm visual analogue scale on the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) pain subscale. The primary outcome was the Osteoarthritis Research Society International/Outcome Measures in Rheumatology Clinical Trials (OARSI/OMERACT) response criterion at week 12. Secondary outcomes included the WOMAC pain score 20% and 50% improvement, WOMAC stiffness and function scores, patient and physician global visual analogue scale, as well as target joint swelling.ResultsTreatment was well tolerated and completed by 17 patients with withdrawals unrelated to lack of efficacy or adverse events. By intention to treat, an OARSI/OMERACT response was recorded in 14 (70%) patients. WOMAC pain 20% and 50% responses were recorded in 14 (70%) patients and eight (40%) patients, respectively. Significant improvement was observed in mean WOMAC pain, stiffness, function, physician and patient global, as well as target joint swelling at 12 weeks (P < 0.0001 for all). After treatment discontinuation, 16 patients were available for assessment at 22 weeks and OARSI/OMERACT response compared with baseline was still evident in 10 (50%) patients.ConclusionTargeting TNFα may be of therapeutic benefit in OA and requires further evaluation in controlled trials.Trial registrationClinicalTrials.gov: NCT00686439.
Highlights
Inflammation associated with synovial expression of TNFa is a recognised feature of osteoarthritis (OA), no studies have yet reported beneficial effects of anti-TNFa therapy on clinical manifestations of inflammation in OA
Results from one study showed that PEGylated soluble tumour necrosis factor (TNF) receptor 1, an antagonist of TNF, inhibited both the increase in type II collagen cleavage by collagenase and the increase in glycosaminoglycan release observed in explant cultures of osteoarthritic articular cartilage [11]
PEGylated soluble TNF receptor 1 and anakinra upregulated aggrecan and type II collagen gene expression in about 50% of OA cartilage explant cultures. These findings suggest that inhibition of TNF may offer a useful therapeutic approach to the management of OA
Summary
Inflammation associated with synovial expression of TNFa is a recognised feature of osteoarthritis (OA), no studies have yet reported beneficial effects of anti-TNFa therapy on clinical manifestations of inflammation in OA. Results from one study showed that PEGylated soluble TNF receptor 1, an antagonist of TNF, inhibited both the increase in type II collagen cleavage by collagenase and the increase in glycosaminoglycan release observed in explant cultures of osteoarthritic articular cartilage [11]. PEGylated soluble TNF receptor 1, either alone or in combination with anakinra, an IL-1 receptor antagonist, frequently downregulated gene expression of matrix metalloproteases MMP1, MMP3 and MMP13 that are involved in cartilage extracellular matrix degradation. PEGylated soluble TNF receptor 1 and anakinra upregulated aggrecan and type II collagen gene expression in about 50% of OA cartilage explant cultures.
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