Prophylaxis after relapse of ANCA-associated vasculitis

June 07, 2020

ANCA-associated vasculitis (AAV) is an autoimmune disease involving vascular inflammation and the formation of autoantibodies (anti-neutrophil cytoplasmic antibodies - ANCA). AAV diseases include a variety of conditions accompanied by the involvement of different organs. The kidneys, lungs and upper respiratory tract are most frequently affected, as are the heart, skin and nervous system. Severe, potentially life-threatening courses of disease are feared. Therapy is with immunosuppressants; conjunctive therapy with glucocorticoids and rituximab (RTX, a monoclonal anti-CD20 antibody) is frequently used for initial remission induction. Recurrent episodes of AAV are not uncommon, especially if relapses have occurred in the past. As the effect of RTX is not persistent, maintenance therapy is required.

The international, multi-center RITAZAREM study was a randomized, controlled (open label) trial of two strategies for preventing relapse in AAV patients after remission induction with RTX and glucocorticoids. The efficacy of fixed interval repeated RTX doses was compared with daily oral azathioprine. If remission was achieved after four months, participants were randomized equally and received either 1000 mg of RTX (every four months, five times in total) or daily doses of azathioprine (2 mg/kg). The follow-up was at least 36 months. At four months, 170 patients were randomized (85 RTX; 85 azathioprine). All patients were followed up for at least 24 months. Median age was 59 (19-89) years, and the duration of the disease was 5.3 years (0.4-38.5). The results showed that rituximab was superior to azathioprine (preliminary HR 0.36; p<0.001): After 24 months (20 months after randomization), 11/85 patients (13%) of the RTX group had relapsed compared to 32/85 patients (38%) of the azathioprine group.

Among the RTX group, only 2/11 relapses (18%) were severe "major relapses", compared to 12/32 (38%) among the azathioprine group. Severe adverse events occurred in 19/85 patients (22%) on RTX, and in 31/85 patients (36%) on azathioprine. As a recognised side effect of RTX, 25/85 patients (29%) developed hypogammaglobulinemia (low immunoglobulin levels as a sign of immunosuppression) and 42/85 patients (49%) had infections (but not severe). Hypogammaglobulinaemia was seen in 25% of the azathioprine group and non-severe infections in 48%.

"AAV is a disease that can be life-threatening and/or lead to kidney failure requiring dialysis, so for that reason it is so important to prevent relapses", explains the study's first author, Dr. Rona Smith, Cambridge, UK. "The study results clearly showed the superiority of RTX over azathioprine during the treatment period, without our finding any evidence that the substance has a worse risk profile - on the contrary."

"The RITAZAREM study is of groundbreaking importance because RTX, as a remission-sustaining therapy, is not recommended for all AAV patients, so it is essential, therefore, to refine the guidelines in future so as to indicate which patient groups benefit most from the therapy," adds ERA-EDTA Press Officer Professor Ron Gansevoort. "This seems to apply especially to maintenance therapy after an early relapse, but possibly also for elderly, frail subjects after a first presentation. Further large-scale studies also need to clarify the optimal RTX dose, the necessary duration of RTX maintenance therapy and other unanswered questions, so that more precise statements can be made in this regard when the guidelines are next revised."
[1] Smith R, Jayne D, Merkel P. A randomized, controlled trial of rituximab versus azathioprine after induction of remission with rituximab for patients with anca-associated vasculitis and relapsing disease. ERA-EDTA 2020, Abstract 4553


With more than 7,000 active members, the ERA-EDTA is one of the biggest nephrology associations worldwide leading European nephrology and one of the most important European Medical Associations. It organizes annual congresses and other educational and scientific activities. ERA-EDTA also produces guidelines, collects data, and performs epidemiological studies through its Registry. The Society supports fellowships and educational/research projects through its committees and working groups. Its publications are NDT, CKJ (Open Access journal), and the online educational journal NDT-Educational.



Related Antibody Articles from Brightsurf:

Antibody evolution may predict COVID-19 outcomes
For COVID-19, the difference between surviving and not surviving severe disease may be due to the quality, not the quantity, of the patients' antibody development and response, suggests a new study.

Can an antibody 'cocktail' prevent COVID-19 infection?
In a new COVID-19 clinical trial, Stuart Cohen at UC Davis Health tests monoclonal antibody combination to prevent COVID-19 in adults exposed to infected patients.

An in-depth analysis of antibody responses to SARS-CoV-2
Using a technology called VirScan to study coronavirus antibody responses in a large cohort of SARS-CoV-2-infected and control individuals, researchers identified epitopes recognized by a large fraction of COVID-19 patients, epitopes cross-reactive with antibodies developed in response to other human coronaviruses, and 10 epitopes likely recognized by neutralizing antibodies.

Tracking antibody profiles for influenza exposures across the lifespan
Immune responses to influenza exposures increase early in life, then decline in middle age, according to a study published July 23 in the open-access journal PLOS Pathogens by Bingyi Yang of the University of Florida, Steven Riley of Imperial College London, Derek Cummings of the University of Florida, and colleagues.

New study ranks performance of currently available COVID-19 antibody tests
Conducted by researchers at NSF International and Novateur Ventures, the peer-reviewed study finds significant variability in the accuracy of available COVID-19 antibody tests.

Ushering an antibody cocktail, designed to reduce antibody resistance, to trial as COVID-19 therapy
Following two studies that screened thousands of human antibodies to SARS-CoV-2 to identify highly potent pairs, in which the antibodies bind non-overlapping regions of the viral target, a resultant antibody cocktail is being tested in human trials.

COVID-19 antibody tests: How reliable are they?
With stay-at-home orders expiring around the world, many hope that COVID-19 antibody testing will help businesses and institutions reopen safely.

A faster way to make antibody-drug conjugates
In a study published today in Science Advances, USC scientists describe a new technology to rapidly create a homogeneous type of ADC, which attaches to a specific site on the cancer cell, with improved efficiency and potentially enhanced stability, effectiveness and safety.

Antibody designed to recognize pathogens of Alzheimer's disease
Researchers have found a way to design an antibody that can identify the toxic particles that destroy healthy brain cells -- a potential advance in the fight against Alzheimer's disease.

New technology can detect anti-virus antibody in 20 minutes
Researchers have succeeded in detecting anti-avian influenza virus antibody in blood serum within 20 minutes, using a portable analyzer they have developed to conduct rapid on-site bio tests.

Read More: Antibody News and Antibody Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to