Two randomized, placebo-controlled trials with similar designs have recently been published, exploring the role of infliximab in treating patients with early GCA and PMR respectively. Disappointingly, both studies came to the same conclusion: Infliximab is of no benefit in either disease.
In the first of these studies, Hoffman and a group of international collaborators investigated the effects of infliximab in patients with GCA. These investigators randomized 44 patients with newly diagnosed GCA (less than four weeks’ duration) in a 2:1 ratio to receive infliximab, 5 mg/kg, or placebo at Weeks 0, 2, and 6, and every eight weeks thereafter. Patients had already achieved remission with GCCs. GCCs were then tapered in a carefully prescribed fashion so that, in the absence of a relapse, GCC dosage of 10 mg/day would be achieved at four months and would be discontinued by six months.
Importantly, as the data in this study indicate, the proportion of patients who were relapse-free through Week 22 (a primary study end point) was similar between infliximab and placebo patients (43% versus 50%; p=0.65).
Further, secondary study end points were also not different between infliximab and placebo groups: cumulative dose of GCCs at Week 22 (3,154 mg versus 3,049 mg; p=0.95); the proportion of patients who remained relapse-free during taper of GCCs to 10 mg/day (61% versus 75%; p=0.31); mean GCC dose at relapse (13.4 mg/day versus 11.8 mg/day; p=0.59); and biochemical markers of inflammation (C-reactive protein, erythrocyte sedimentation rate, and interleukin-6 levels).
There was no difference in the proportion of patients who achieved complete remissions, defined as no sign of active GCA for at least 12 weeks after cessation of GCCs: 39% versus 44% (p=1.00). Of the patients who achieved complete remission, 73% of the infliximab group and 86% of the placebo group later had a relapse. Of note, there was no difference in the frequency of adverse events or serious adverse events between the two groups. Thus, while the addition of infliximab was safe, it did not add benefit.
In view of the putative role of cytokines in the pathogenesis of GCA, these results may appear surprising. There are several explanations for the failure of infliximab to show activity. The authors acknowledge that a higher dose of infliximab might have been efficacious. Also, methotrexate was not administered concomitantly with infliximab and this might have altered efficacy. However, only about one-quarter of patients developed anti-infliximab antibodies 20 weeks after the last dose was administered, so that lack of efficacy could not be attributed to anti-drug antibodies.
