In a related study, Salvarani and Italian colleagues investigated the effects of TNF blockade on patients with PMR. These investigators randomized 51 patients with newly diagnosed PMR (mean duration of symptoms before therapy of 10 to 11 weeks) in a 1:1 ratio to receive infliximab, 3 mg/kg, or placebo infusions at Weeks 0, 2, 6, 14, and 22. All patients received prednisone 15 mg for the first four weeks, which was then tapered at four-week intervals to 15 mg, 10 mg, 5 mg, and 2.5 mg daily dosages. Patients with clinical or histological evidence of GCA were excluded.
I do not routinely add second-line agents in my new patients with giant cell arteritis and polymyalgia rheumatica, but I am aggressive in trying to minimize adverse effects of glucocorticosteroids.
The proportion of patients free of relapse at 52 weeks—the primary end point—was not different between infliximab and placebo groups, and the groups also did not differ in all secondary end points, including the proportion of patients without relapse at Week 22 (55% versus 54%; p=1.00); the proportion of patients no longer taking GCCs at Week 22 (55% versus 64%; p=0.56) or Week 52 (50% versus 54%; p=1.00); median relapses in all patients (one versus one; p=0.69); median cumulative dose of prednisone at 52 weeks (17.1 gm versus 12.2 gm; p=0.31). There was no difference in adverse drug events (eight in each group).
The authors acknowledge several limitations of the study. Patients all had newly diagnosed PMR. Pathophysiological studies show an association between high TNF-a production and steroid-resistant disease. Could infliximab have a beneficial role in more chronic PMR? Also, the dose of infliximab was low—3 mg/kg—and prednisone was tapered quickly over 16 weeks, which could have contributed to the high frequency of flare-ups.
These two studies will probably put an end to investigations on the use of infliximab as a steroid-sparing agent for GCA and PMR. The studies are small and the confidence intervals were wide for most outcomes in both studies. While it is possible that a small beneficial effect could exist for infliximab in these diseases, the expense of this agent probably would preclude its cost-effectiveness for relatively small potential benefits.
The search for good alternatives to GCCs will undoubtedly continue—and it should because the side effects of this therapy are high in older patients. Because of evidence that other cytokines—notably interleukin-1, interleukin-6, and interferon-gamma—contribute to vascular inflammation in GCA, it is likely that these cytokines will be targeted in future trials.