The Efficacy and Safety of Rituximab in ANCA-Associated Vasculitis: A Systematic Review

Abstract

Background and aim: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare multisystem autoimmune disease developed by autoantibody production against human neutrophilic granulocytes, including proteinase-3 (PR3) and myeloperoxidase (MPO). The management of AAV patients is difficult due to the multiorgan involvement, high rate of relapse, and complications of immunosuppressive agents that make it challenging. This study aims to investigate the efficacy and safety of rituximab (RTX) therapy in patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) subtypes. Method: The PubMed/Medline database was searched for any studies related to RTX therapy in ANCA-associated vasculitis (GPA and MPA subtypes), from inception to 1 August 2022, and proceeded in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Results: Our search resulted in 1082 initial records. After the elimination of review papers, irrelevant studies, and non-English records, 223 articles were included, and the data related to the efficacy and safety of RTX therapy were extracted. Several randomized and non-randomized studies showed that RTX is an effective treatment option for patients with AAV. Most of the studies showed the very effective effect of RTX in controlling disease in AAV patients, including pediatrics, adults, and elderlies, although RTX cannot completely prevent relapse. However, maintenance therapy helps delay the disease’s relapse and causes sustained remission. Not only the licensed dose (375 mg/m2 intravenous per week for 4 weeks) could induce disease remission, but studies also showed that a single infusion of RTX could be effective. Although RTX could resolve many rare manifestations in AAV patients, there are few reports showing treatment failure. Additionally, few sudies have reported the unexpeted worsening of the disease after RTX administration. Generally, RTX is relatively safe compared to conventional therapies, but some serious adverse effects, mainly infections, cytopenia, hypogammaglobinemia, malignancy, and hypersensitivity have been reported. Conclusions: RTX is an effective and relatively safe therapeutic option for AAV. Studies on the evaluation of the safety profiles of RTX and the prevention of severe RTX-related side effects in AAV patients are required.

The Role of Electroencephalography in the Prediction of Relapse of Febrile Convulsion in Patients Aged Between 6 to 60 Months: A Prospective Cohort Study

“…18,19 However, some other committees of the American Academy of Neurology, The Child Neurology Society, and The American Epilepsy Society have noted that EEG can predict further episodes of seizure and recommend considering the EEG as an initial diagnostic tool after the first episode of FS. [20][21][22] Therefore, the role of EEG for patients with FS is not conclusive. However, some demographic and clinical factors investigated do predict abnormal EEG findings in patients with complex FS, including age >3 years and abnormal neurological investigations, as well as conducting EEG within first 7 days after FS.…”

“…18,33,35 On the other hand, epileptiform discharges found in EEG are not predictive of RFS but are remarkable for the development of epilepsy and frontal paroxysms in EEG. 12,21 Little is known about the pseudopetit mal discharge (PPMD) on EEG. PPMD refers to paroxysmal discharges that occur during drowsiness.…”

Efficacy and safety of avacopan in patients with ANCA-associated vasculitis receiving rituximab in a randomised trial

“…The rate of sustained remission can be increased by continuing treatment with prednisolone, as in the RITUXVAS trial in which sustained remission at month 12 was achieved by 76% of patients receiving RTX for induction of remission with continued prednisolone at a dose of 5 mg daily for 12 months 29. Sustained remission can also be achieved by repeated doses of RTX; however, more than 40% of patients experience a relapse after the withdrawal of RTX 30–33. For comparison, this subgroup analysis reports relapse rates after remission at any time of 20.2% for the prednisone taper group and 8.7% for the avacopan group at 52 weeks among patients who achieved BVAS of 0 at any time, suggesting that the addition of avacopan reduced the rates of relapse.…”

“…29 Sustained remission can also be achieved by repeated doses of RTX; however, more than 40% of patients experience a relapse after the withdrawal of RTX. [30][31][32][33] For comparison, this subgroup analysis reports relapse rates after remission at any time of 20.2% for the prednisone taper group and 8.7% for the avacopan group at 52 weeks among patients who achieved BVAS of 0 at any time, suggesting that the addition of avacopan reduced the rates of relapse. Consistent with the rates of remission reported in other trials, in the current analysis, patients who received background therapy with RTX without redosing and were randomised to a 20-week prednisone taper had a rate of sustained remission of 56.1% at week 52.…”

Promising Experimental Treatments for Lupus Nephritis: Key Talking Points and Potential Opportunities

“…40,41 Rituximab has long been successfully used in rheumatoid arthritis patients and vasculitis. 42,43 However, the predicted B-cell depleting therapy benefit in SLE patients has been harder to demonstrate in clinical trials.…”