Background The dynamics of B cell reconstitution in relapsing or refractory ANCA-associated vasculitides (AAV) treated with rituximab (RTX) followed by standard immunosuppressants are not clear. While in patients with rheumatoid arthritis B cell repopulation generally starts 6 to 9 months after RTX therapy, an impaired early B-lymphocyte development resulting in a protracted peripheral B cell repopulation was reported recently in some AAV patients after B cell depletion with RTX.
Objectives This is of clinical importance as the relapse rates in AAV after discontinuation of RTX therapy are high, and there are no data on safety and efficacy of RTX retreatment in persistently B cell depleted patients. Furthermore, there are no defined parameters that could guide RTX retreatment. To date the frequency of AAV patients with impaired peripheral B cell regeneration and the mechanism leading to the constricted regenerative capacity of the B cell compartment are unknown.
Methods We analysed in a single center cohort comprising 125 patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) the B cell repopulation kinetics in 37 patients treated for relapsing or refractory disease with RTX followed by maintenance immunosuppressants in most patients. Furthermore, we report on serum concentrations of the B cell-activating factor of the TNF family (BAFF, BLyS) and immunoglobulin concentrations as well as on peripheral B cell subpopulations in a subgroup of patients that relapsed after RTX treatment.
Results B cells were re-detectable in only one patient within the 9 months period after RTX treatment. After a mean observation time of 21 months 14 patients (41%) had started repopulating the peripheral B cell compartment, with 7 of the 14 patients having re-detectable B cells within the first year after RTX treatment. In 20 patients (59%) no repopulation occurred within the observation period. Eight of these patients were observed for more than 24 months without a starting B cell repopulation. BAFF concentrations in serum of AAV patients after RTX treatment were increased compared to healthy controls and correlated inversely with peripheral B cell numbers, IgG- and IgA concentrations. Serum immunoglobulin concentrations declined significantly after RTX treatment, and serum IgG concentrations correlated with peripheral B cell numbers after RTX therapy. 13 patients relapsed after RTX treatment. All of the 13 relapses either occurred after beginning B cell reconstitution or were accompanied by rising ANCA titres. In patients that relapsed after RTX the B lymphocyte compartment consisted mainly of switched memory B cells.
Conclusions In summary, in our cohort of GPA and MPA patients treated with RTX followed by a standard maintenance immunosuppressive therapy a high proportion of patients had a long-lasting B cell depletion. Retreatment with RTX in long-term B cell depleted patients warrants close monitoring for adverse events and especially infectious complications and monitoring of serum immunoglobulin. Relapses after RTX treatment either occurred after beginning B cell reconstitution or were accompanied by rising ANCA titres.
Disclosure of Interest None declared
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