Carlo Salvarani, MD; Gene G. Hunder
Potential Financial Conflicts of Interest: None disclosed.
Salvarani C., Hunder G.; Tumor Necrosis Factor–Blocking Agents in Polymyalgia Rheumatica and Giant Cell Arteritis. Ann Intern Med. 2008;148:167-168. doi: 10.7326/0003-4819-148-2-200801150-00018
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Published: Ann Intern Med. 2008;148(2):167-168.
TO THE EDITOR:
We agree with the conclusions of the insightful editorial by Luqmani (1) about the 2 randomized, controlled trials (RCTs) of infliximab in polymyalgia rheumatica (2) and giant cell arteritis (GCA) (3), especially that corticosteroids are still the cornerstone of treatment for these 2 related diseases. However, although these 2 studies showed that adding infliximab to prednisone is of no benefit in patients with GCA or polymyalgia rheumatica, a corticosteroid-sparing effect for tumor necrosis factor (TNF) blockers in these 2 conditions cannot be completely excluded. As Luqmani pointed out, the 2 trials were designed to detect a large effect of infliximab because of the drug's expense and possible adverse effects. They were too small to definitively identify small benefits. Another argument can be made for a possible therapeutic benefit for TNF-blocking agents. The 2 RCTs enrolled patients with newly diagnosed polymyalgia rheumatica and GCA. Two open, pilot studies that preceded these RCTs observed the efficacy of infliximab in reducing corticosteroid requirements in patients with long-standing, relapsing polymyalgia rheumatica and GCA (4, 5). In these patients, the potent anti-inflammatory effect of infliximab was demonstrated by the reduction of acute-phase reactants, including interleukin (IL)-6 circulating levels, 2 weeks after the start of therapy. The reduction in IL-6 levels was of particular interest, because the persistence of elevated levels of this cytokine characterized the patients with continued active disease who require higher and more prolonged doses of corticosteroids (4). It is possible that TNF-blocking agents are effective in subsets of patients with polymyalgia rheumatica and GCA characterized by a more chronic, relapsing course. A third recent open study from our group suggests that etanercept may be another useful corticosteroid-sparing agent in patients with polymyalgia rheumatica and refractory disease—that is, patients with more severe disease (6). The efficacy of TNF-blockers in patients with relapsing disease also has a pathophysiologic basis. The elegant study by Hernández-Rodrguez and colleagues (7) showed that high TNF-α production in GCA was associated with longer steroid requirements and relapsing disease. Therefore, before completely excluding a potential therapeutic role for TNF-blockers in polymyalgia rheumatica or GCA, we suggest that RCTs be performed enrolling only patients with relapsing or refractory polymyalgia rheumatica and GCA.
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