LAUSR

We thank Misra et al. for their interest in our paper on the role of similar biological rituximab in remission induction and maintenance in granulomatosis with polyangiitis [1, 2]. They reviewed the available published literature on the use of biosimilars in vasculitis, which nicely highlights the sparsity of such data. They used the Newcastle-Ottawa quality assessment scale for cohort studies to grade all the published studies. Three components of this scale are “selection,” “comparability,” and “outcome.” Since most of the published studies did not have a comparator arm, they proposed that the future observational studies should have a representative comparator group, and the issue of switching from innovator to biosimilar should also be addressed. While such studies have been done in rheumatoid arthritis and non-Hodgkin’s lymphoma, these would be very difficult to do in rare diseases like vasculitis [3]. Efficacy of rituximab in ANCA-associated vasculitis (AAV) has been established in randomized trials as well as real-world setting [4]. Data from the Indian registries has shown that rituximab is the most commonly prescribed similar biologic [5]. However, there is dearth of evidence for rituximab biosimilar use in AAV. Besides our study, an abstract of a retrospective study comparing innovator and similar biologic rituximab used in conditions like AAV, lupus nephritis, minimal change disease, IgG4 disease, and ABOincompatible transplant was presented at the 56th ERAEDTA congress. Their subgroup analysis in AAV showed higher relapses in the innovator group (p = 0.04) but the innovator group had a much longer median follow-up (median 3.4 vs 0.4 years, p < 0.001) [6]. Designing a randomized trial comparing similar biologic with the originator in patients with vasculitis, though ideal, may not be practical due to rarity of AAV and also due to cost constraints. Moreover, while randomized controlled trials are the gold standard for evidence-based medicine, they may not always be truly representative of the actual disease population. These trials are conducted in an ideal setting of a homogenous population, but the real-world scenarios, especially in the developing nations, are far from ideal. The real-life experiences in such a setting might help bridge this knowledge gap, like serious adverse events have been previously reported with rituximab-intended copies from Mexico and Colombia [7]. Long-term drug safety data derived from real-world use may thus supplement the data obtained from controlled trials [8]. Many questions remain unanswered and are avenues for future research comparing similar biologic and innovator rituximab in AAV. Some of these are long-term efficacy and safety, comparison of different rituximab dosing regimens, extent of B cell depletion, hypogammaglobulinemia, immunogenicity, switching, substitution, and interchangeability. Until the time such data is available from randomized trials, real-life data can provide an evidence base for use of similar biologic rituximab in AAV.