Rituxan-Soliris Combo May Replace Glucocorticoids in Treatment of Severe AAV, Case Report Suggests

Rituxan-Soliris Combo May Replace Glucocorticoids in Treatment of Severe AAV, Case Report Suggests

A combination of Rituxan (rituximab) and Soliris (eculizumab) may be used to replace glucocorticoids for the treatment of patients with severe ANCA-associated vasculitis, a case report suggests.

The report, “Glucocorticoid-free induction regimen in severe ANCA-associated vasculitis using a combination of rituximab and eculizumab,” was published in the journal Reumathology.

Anti-neutrophil cytoplasmic autoantibody (ANCA) vasculitis, or AAV, is an autoimmune disease caused by the production of autoantibodies — antibodies that wrongly target and attack the host’s own cells and tissues — leading to blood vessel inflammation and damage to affected tissues and organs.

Recent studies in animal models have suggested the complement system — a set of more than 30 blood proteins that form part of the body’s immune defenses — might be involved in the overactivation of the immune system in AAV, meaning it could be a relevant target for therapeutic interventions.

Data from a Phase 2 clinical trial (NCT01363388) demonstrated that treatment with avacopan (CCX168), an investigational inhibitor of the complement C5a receptor, could effectively help manage AAV instead of using high doses of glucocorticoids.

Glucocorticoids are currently considered the standard treatment for patients with severe AAV. However, their long-term use has been associated with a variety of side effects, including diabetes, heart disease, infections, and osteoporosis. For this reason, research has focused on finding alternative therapies that still enable patients to go into remission, while avoiding potentially serious side effects from treatment.

In this report, French researchers described the case of a patient with severe AAV whose symptoms were kept under control using a glucocorticoid-free combination of immunotherapy Rituxan (sold by Genentech) and Soliris (by Alexion), another C5 blocking agent similar to avacopan.

In September 2018, the 77-year-old woman was referred to the Centre de référence des maladies rénales rares in Toulouse during her third AAV relapse.

Between March 2015 and January 2017, she had received a combination of glucocorticoids and azathioprine to treat a rapidly progressing glomerulonephritis (kidney inflammation) associated with ANCA.

In May 2017, she experienced a life-threatening relapse and was treated with glucocorticoids, plasma exchanges, and six pulses of intravenous cyclophosphamide, followed by a maintenance therapy of glucocorticoids in combination with Rituxan.

Shortly after, she developed a serious lung infection requiring two admissions to the intensive care unit.

Because of her history of relapses and serious infections, an immunosuppressive treatment course of glucocorticoids was ruled out when her third relapse occurred. Instead, she started taking a combination therapy of Rituxan (375 mg/m2 on the first and seventh days) and Soliris (900 mg once a week for one month, followed by 1,200 mg bimonthly).

“We used a C5 blocking agent because Avacopan is not still available in France,” the researchers said.

In December 2018, she had no complaints of symptoms related to AAV and was taken off Soliris and kept on a maintenance therapy with Rituxan (500 mg every six months). No relapses occurred over the following 16 weeks after she stopped taking Soliris.

“We showed for the first time that [Soliris] … may also be used as a salvage therapy in patients with active AAV with a contraindication for glucocorticoids,” the researchers wrote. Still, “whether C5 or C5aR blocking agents may also be used as salvage therapy in patients with refractory AAV remains to be addressed.”

Joana holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from Universidade de Lisboa. She is currently finishing her PhD in Biomedicine and Clinical Research at Universidade de Lisboa. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells — cells that made up the lining of blood vessels — found in the umbilical cord of newborns.
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Joana holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from Universidade de Lisboa. She is currently finishing her PhD in Biomedicine and Clinical Research at Universidade de Lisboa. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells — cells that made up the lining of blood vessels — found in the umbilical cord of newborns.
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