Long-term follow-up of different refractory systemic vasculitides treated with rituximab

Nottingham University Hospitals NHS Trust, Queen's Medical Centre Campus, Derby Road, Nottingham, UK.
Clinical Rheumatology (Impact Factor: 1.77). 04/2011; 30(9):1241-5. DOI: 10.1007/s10067-011-1756-8
Source: PubMed


There is increasing interest in rituximab (RTX) as an alternative to cyclophosphamide (CYC) for remission induction in systemic vasculitis. Recent studies have reported high remission rates, but it is not clear how long the initial remission lasts [1, 2]. A retrospective study was undertaken of 15 cases of refractory systemic vasculitis (11 Wegener's granulomatosis, 1 Churg-Strauss syndrome, 1 cutaneous polyarteritis nodosa and 2 cryoglobulinaemic vasculitis) treated with RTX, with a mean follow-up of 34 months. All had previously received CYC, and 14, at least one other immunosuppressive drug. All had active disease when treated (median Birmingham Vasculitis Activity Score (BVAS) 2003, 13). All cases achieved remission (BVAS 2003, 0). Thirteen required re-treatment, nine due to relapse (mean, 9 months after initial treatment) and four because of repopulation or rising ANCA in the context of CYC intolerance or previous CYC refractory disease. Relapsing cases have been successfully re-treated up to five further cycles, either at B cell repopulation or at six monthly intervals. Infections were rare. Mean IgG levels fell significantly, and IgM levels became subnormal in six cases. There were three cases of neutropenia, one severe at 10 months post-treatment. These results provide further evidence that RTX is an effective induction agent in systemic vasculitis. The optimal and long-term outcome of re-treatment remains to be defined.

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    • "Efficacy of RTX therapy was significant in the majority of cases, as shown in Table 1. Objective documentation of baseline disease activity (baseline BVAS) was recorded in 59 patients [12] [13] [16] [17] [19] [22] and at last follow-up in 55 [17] [19] [22]. In the largest case series of 41 patients, median BVAS dropped from 11 to 1 at 12 months [22], while in the nine patients reported by Thiel et al. [19], median BVAS dropped from 14 to 3 at 9 months. "
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    ABSTRACT: Rituximab is approved for the treatment of granulomatosis with polyangiitis and microscopic polyangiitis. Our objective was to review published clinical evidence on the efficacy of rituximab in the treatment of eosinophilic granulomatosis and polyangiitis (EGPA). We describe a case of refractory EGPA with severe vasculitic neuropathy, which responded impressively to B-cell-depleting therapy. A systematic search of the English literature was also performed to capture all available clinical evidence on the use of rituximab in EGPA. We identified a total of 73 EGPA patients who have been treated with rituximab, all data coming from case series or isolated case reports. The majority of patients (85.1%) were treated for refractory or relapsing disease; a mean (SD) of 2.1 (0.9) different immunosuppressive agents were used prior to rituximab administration. Efficacy of RTX therapy was significant in the majority of cases and in a wide variety of disease manifestations; however, a lack of standardized assessment of disease activity before and after treatment was observed in many reports. Overall, 54.0% of patients were treated with a single cycle of rituximab and only 10.8% experienced relapses of the disease. Few significant side effects were observed during a highly variable period of follow-up (3 months to 5 years), mainly severe infections and allergic reactions. RTX seems to be effective in cases of severe EGPA refractory to standard of care immunosuppressive treatment, although support comes from case reports and non-controlled studies. Copyright © 2015 Elsevier Inc. All rights reserved.
    Seminars in arthritis and rheumatism 03/2015; 45(1). DOI:10.1016/j.semarthrit.2015.03.004 · 3.93 Impact Factor
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    • "Thus, although RTX can be recommended as a suitable alternative to CYC for induction therapy, several questions remain unanswered, like the correct dosing. Although both RITUXVAS [19] and RAVE [20] trials used 375 mg/m 2 of body-surface area per week for 4 weeks, some observational studies have suggested that similar results can be achieved with two doses of 1 g of RTX given 2 weeks apart [48] [51] [54] [64] [66]. It is not known whether RTX is also effective in ANCA-negative patients or in patients with limited disease, and as stated above, the long-term safety issue is still unclear. "
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    ABSTRACT: Objective Relapses and failure are frequent in systemic vasculitis (SV) patients. Biological agents have been prescribed as rescue therapies. The aim of this systematic review is to analyze the current evidence on the therapeutic use of biological agents for SV. Methods MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials were searched up to the end of April 2013. Systematic reviews and meta-analysis, clinical trials, cohort studies, and case series with >3 patients were included. Independent article review and study quality assessment was done by 2 investigators with consensus resolution of discrepancies. Results Of 3447 citations, abstracts, and hand-searched studies screened, 90 were included. Most of the studies included ANCA-associated vasculitis (AAV) patients and only a few included large vessel vasculitis (LVV) patients. Rituximab was the most used agent, having demonstrated efficacy for remission induction in patients with AAV. A number of studies used different anti-TNFα agents with contrasting results. A few uncontrolled studies on the use of abatacept, alemtuzumab, mepolizumab, and tocilizumab were found. Conclusion Current evidence on the use of biological therapies for SV is mainly based on uncontrolled, observational data. Rituximab is not inferior to cyclophosphamide for remission induction in AAV and might be superior in relapsing disease. Infliximab and adalimumab are effective as steroid-sparing agents. Etanercept is not effective to maintain remission in patients with granulomatosis with polyangiitis, and serious adverse events have been reported. For LVV, both infliximab and etanercept had a role as steroid-sparing agents, and tocilizumab might be effective also for remission induction in LVV.
    Seminars in arthritis and rheumatism 02/2014; 43(4):542–557. DOI:10.1016/j.semarthrit.2013.07.010 · 3.93 Impact Factor
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    • "This constitutes a therapeutic dilemma. Autoimmune manifestations may be life threatening, but on the other hand, methods of treatment of autoimmune diseases are associated with increased risks of sepsis [25–27]. "
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    ABSTRACT: To identify differences in treatment and outcome of various types of glomerulonephritis developing in the course of infections triggering antineutrophil cytoplasmic antibody (ANCA) formation, we analyzed published reports of 50 patients. Immunosuppressives were added to antibiotics in 22 of 23 patients with pauci-immune glomerulonephritis. Improvement was noted in 85% of 20 patients with information on outcomes. Death rate was 13%. Corticosteroids were added to antibiotics in about 50% of 19 patients with postinfectious glomerulonephritis. Improvement rate was 74%, and death rate was 26%. Two patients with mixed histological features were analyzed under both pauci-immune and post-infectious glomerulonephritis categories. In 9 patients with other renal histology, treatment consisted of antibiotics alone (7 patients), antibiotics plus immunosuppressives (1 patient), or immunosuppressives alone (1 patient). Improvement rate was 67%, permanent renal failure rate was 22%, and death rate was 11%. One patient with antiglomerular basement disease glomerulonephritis required maintenance hemodialysis. Glomerulonephritis developing in patients who became ANCA-positive during the course of an infection is associated with significant mortality. The histological type of the glomerulonephritis guides the choice of treatment. Pauci-immune glomerulonephritis is usually treated with addition of immunosuppressives to antibiotics.
    02/2013; 2013. DOI:10.5402/2013/324315
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