Rituximab and Fcγ Receptors in Granulomatosis With Polyangiitis (Wegener's): Comment on the Article by Cartin‐Ceba et al

opinion. This is in part because there is no firmly established standard of care that optimally balances efficacy and toxicity. In these 2 trials, all participants initially received prednisone at a dosage of 40–60 mg/day, as selected by their site investigator. This dosage was not calculated based on body weight, but there was latitude within the dosage range to take this factor into account. The prednisone tapering schedule was such that all patients reached a dosage of 20 mg/day at week 12, which was then reduced more slowly until discontinuation at week 28. Several factors were taken into consideration when designing this prednisone-tapering schedule. The duration of glucocorticoid treatment was similar to that used in previously published multicenter randomized trials in GCA (1,2). Notably, a recent large trial in GCA included a group with a 26-week taper (3). Another reason for selecting this tapering schedule was recognition of the clinical need for treatment options that provide a means to reduce glucocorticoid exposure. There would likely be limited enthusiasm for use of a biologic therapy from the standpoint of side effects and cost unless the agent were found to have both a statistically significant and clinically meaningful difference when measured against prednisone. Our trial demonstrated that abatacept combined with prednisone reduced the risk of relapse of GCA compared with prednisone alone, through a design that searched for a large difference between treatment arms using a 28-week prednisone taper; this observed difference has clinical relevance and meaning. Because both treatment groups had the same exposure to prednisone, any impact of the tapering schedule on the relapse rate would have affected both arms equally and therefore would not bias the comparison. The finding that there was no increase in the frequency or severity of adverse events with the addition of abatacept was an important secondary end point in our studies. Although we cannot speculate on whether there would be a difference with a longer course of prednisone, the side effect profile of glucocorticoids and the ability to reduce the amount of glucocorticoid exposure are the main reasons why pursuing novel therapeutic agents remains critical in GCA and TAK. The letter from Dr. Moiseev and colleagues raises several interesting points regarding disease activity assessment in TAK and the relationship between GCA and TAK. We agree that determining active disease remains one of the greatest challenges in large vessel vasculitis. The definitions used in our trials were determined by the Steering Committee of the Vasculitis Clinical Research Consortium based on clinical and imaging parameters used in practice, outcomes used in prior clinical research in TAK, and experience with GCA. As observed in our study, the vascular and inflammatory manifestations that can prompt a change in treatment are seen during the time span of a trial. It is also of interest that although cardiovascular parameters are perceived as being long-term outcomes, 3 of our 26 randomized TAK patients had evidence by imaging of a new vascular lesion in a new territory during the trial. However, we strongly agree with the enthusiasm to explore promising outcome measures in large vessel vasculitis, including patientreported outcomes, biomarkers, and novel imaging techniques. The question as to whether TAK and GCA are unique or part of a single disease spectrum has been of great interest (4,5), with evidence available to support both conclusions. The divergent efficacy of abatacept in our side-by-side randomized trials in GCA and TAK raises intriguing questions about the relationship between these diseases and the need for ongoing clinical and pathophysiologic investigation. While these studies cannot answer the question of whether GCA and TAK are different entities, they demonstrate the value of examining these diseases separately and in parallel when possible. Both letters raise points about the clinical application of the findings from these trials. We agree that physicians must consider many factors when deciding how these results apply to the care of their patients. In the TAK trial, the addition of abatacept to prednisone did not reduce the risk of relapse. Although we agree that individual patients may respond differently, we cannot advocate for the routine use of a therapy that did not show benefit in an adequately powered randomized trial. The GCA study did demonstrate a statistical difference in the rate of relapse-free survival in patients who received abatacept combined with glucocorticoids. However, the strengths and limitations must continue to be weighed by each physician when choosing how to interpret and utilize these results.