London, United Kingdom—The search for effective treatments for osteoarthritis (OA) has been elusive, with little or no progress regarding treatments that can slow disease progression. Two studies presented at the 2016 European League Against Rheumatism Annual Congress suggest that treatment with anti–tumor necrosis factor (TNF) agents may have potential in slowing disease progression in patients with hand OA.1,2 These are still early days, but together, these studies suggest that anti-TNF agents may find a role in slowing disease progression in patients with hand OA.
Presence of TNF in Affected Joints
Ruth Wittoek, MD, PhD, Rheumatologist, Department of Rheumatology, Ghent University, Belgium, and lead author of the first study explained that there are no animal models of hand OA, and it is difficult to obtain biopsies or fluid aspiration from small finger joints affected with hand OA.1 Using scintigraphy, Dr Wittoek and her coauthors took static images of both hands of 5 patients with erosive OA <15 minutes after administration of radiolabeled certolizumab pegol (early phase), and again 4 to 6 hours posttreatment (late phase).
In the early phase, uptake of the radiolabeled anti-TNF agent was observed in 7 (7.8%) joints, but was quantitated as weak. In the late phase, uptake was observed in 24 (26.7%) joints, with 5 described as strong and the remaining 19 described as weak. No uptake of the radiolabeled anti-TNF was seen in metacarpophalangeal joints. Uptake of the radiolabeled anti-TNF agent was linked to signs of disease activity, including tender, swollen, and radiographically active joints. Late uptake was present in 12 (36.4%) of 33 tender joints, and 12 (21.1%) of 57 nontender joints. Late uptake was present in 18 (29%) of 62 active joints, but only 6 (21.4%) of 28 noninflamed joints.
“Soft-tissue swelling strongly correlated with uptake of certolizumab pegol, meaning a lot of TNF was present in these joints,” Dr Wittoek explained. “These data further solidify the rationale for cytokine-directed therapies in OA.”
Etanercept Benefits in Hand OA
Results from a multicenter, double-blind, randomized, placebo-controlled trial demonstrated that etanercept has benefits related to pain relief and structural damage in patients with hand OA.2 The study involved 90 patients (mean age, 60 years) randomized to treatment for 1 year with subcutaneous etanercept 50 mg weekly—for 24 weeks, then 25 mg per week for the remainder of the year—versus placebo.
Etanercept did not meet the primary end point of the trial, which was level of OA pain assessed on a visual analog scale (VAS) at 24 weeks. However, etanercept was superior to placebo for pain and structural damage assessed by the Ghent University Scoring System (GUSS) in patients who were symptomatic, had inflammatory disease, and completed the study. The drug was particularly effective in joints with signs of inflammation, noted lead author Margreet Kloppenburg, DM, Rheumatology, Clinical Epidemiology, Leiden University Medical Center, The Netherlands.
Although the difference between the 2 treatment arms was not statistically significant on the VAS pain scale, an intent-to-treat analysis showed numerical differences favored etanercept. An interaction was observed between soft swelling/erythema and etanercept treatment on GUSS, and the difference favoring etanercept over placebo was statistically significant (P <.05).
Effect on Bone Marrow Lesions
A separate analysis of this study suggested that treatment with etanercept can inhibit bone marrow lesions in patients with hand OA.3
In 20 patients with symptomatic erosive OA and signs of inflammation in ≥1 interphalangeal joints, contrast magnetic resonance images were obtained of joints at baseline and 1 year; images were scored for synovitis and bone marrow lesions. The presence of bone marrow lesions were associated with the erosive and remodeling phases of erosive hand OA.
The beneficial effect of etanercept on bone marrow lesions was more pronounced in joints with synovitis at baseline. The study authors theorize that the beneficial effect of etanercept on bone marrow lesions is because of an interaction between synovium and subchondral bone that could be influenced by blocking TNFs.
- Wittoek R, Carron P, Lanbert B, et al. Immunoscintigraphic detection of TNF by radiolabeled certolizumab pegol in patients with erosive hand osteoarthritis in relation to disease activity and structural progression: a proof of concept study. Presented at: 2016 European League Against Rheumatism Annual Congress; June 8-11, 2016; London, United Kingdom. Abstract OP0097.
- Kloppenburg M, Ramonda R, Kwok WY, et al. Randomized, placebo-controlled trial to evaluate clinical efficacy and structure modifying properties of subcutaneous etanercept (ETN) in patients with erosive inflammatory hand osteoarthritis (OA). Presented at: 2016 European League Against Rheumatism Annual Congress; June 8-11, 2016; London, United Kingdom. Abstract OP0095.
- Kroon FP, Wittoek R, Verbruggen G, et al. Effect of etanercept on synovitis and bone marrow lesions in the erosive hand osteoarthritis. Presented at: 2016 European League Against Rheumatism Annual Congress; June 8-11, 2016; London, United Kingdom. Abstract OP0098.