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Edited by Yimaitong, please do not reprint without authorization
.
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of rare autoimmune diseases characterized by inflammation of the blood vessel wall, including granulomatous polyangiitis (GPA) and microscopic polyangiitis (MPA) and eosinophilic granulomatous polyangiitis (EGPA)
.
In 2021, the AAV management guidelines jointly issued by the American College of Rheumatology (ACR) and the Vasculitis Foundation pointed out that for active severe AAV, rituximab can be used to induce remission treatment; severe GPA/MPA patients receive cyclophosphamide or After rituximab treatment has achieved remission, rituximab can be used for subsequent maintenance remission treatment; rituximab can also be used for the treatment of recurrent AAV
.
So, what is the "charm" of rituximab? Recently, the journal J Clin Med.
(impact factor 4.
241) released a review to summarize randomized controlled trials of rituximab (RTX) in the treatment of AAV, and summarize its efficacy and safety in AAV induction and maintenance therapy
.
Rituximab can effectively induce remission, not inferior to cyclophosphamide.
In 2011, the U.
S.
Food and Drug Administration (FDA) approved RTX (375 mg/m2/w, intravenous injection, for 4 consecutive weeks) combined with glucocorticoid ( GC) Treatment of GPA/MPA
.
The approval is based on two random trials, RAVE and RITUXVAS
.
Studies have shown that in patients with new-onset and relapsed GPA/MPA, the efficacy of RTX to induce remission is not inferior to cyclophosphamide
.
The RAVE study included 197 patients with GPA/MPA and compared the efficacy of 375 mg/m2/w RTX and oral cyclophosphamide (2 mg/kg/d) for 4 weeks to induce remission
.
The data show that there is no significant difference in the efficacy of the two
.
The RITUXVAS study included 44 newly diagnosed GPA/MPA patients with renal impairment.
The results also showed that there was no significant difference in the efficacy of RTX and cyclophosphamide in inducing remission
.
It should be noted that none of the published RTX-related studies included patients with EGPA
.
According to the recently released systematic review of RTX treatment of EGPA, in both new-onset and recurrent EGPA patients, RTX induction therapy is effective, and patients with ANCA-positive EGPA may benefit more
.
However, more randomized controlled studies are needed to confirm the efficacy of RTX in the treatment of EGPA
.
Rituximab can effectively maintain remission and has better efficacy than azathioprine.
In addition, RTX is also recommended for maintaining remission in patients with GPA and MPA
.
Researches related to RTX maintenance treatment include MAINRITSAN, RITAZAREM, MAINRITSAN2, MAINRITSAN3
.
The MAINRITSAN study enrolled 115 AAV patients.
All patients received RTX or azathioprine maintenance therapy after treatment with hormones combined with cyclophosphamide to achieve remission
.
The results showed that during the 60-month follow-up, the RTX regimen was superior to azathioprine (AZA) in preventing recurrence
.
The RITAZAREM study included patients with relapsed AAV, and all patients received RTX combined with GC induction therapy
.
After achieving remission, the patient received maintenance therapy with RTX (1000 mg every 4 months for a total of 5 doses) or AZA (2 mg/kg/d)
.
The results show that RTX is better than AZA in preventing recurrence
.
The MAINRITSAN2 study shows that in addition to the 500mg/time dose, lower doses can also achieve the effect of maintaining remission
.
The MAINRITSAN3 study shows that after 18 months of maintenance treatment, extending the RTX treatment time (500 mg injection every 6 months for another 18 months) can effectively maintain remission and reduce recurrence
.
Rituximab has good safety in the treatment of AAV.
With the improvement of the prognosis of AAV patients, the safety of long-term treatment is increasingly valued
.
In the treatment of RTX, infection and infusion reactions are the most common adverse events
.
Infections associated with RTX therapy may be related to secondary hypogammaglobulinemia
.
Among AAV patients treated with RTX, hypogammaglobulinemia is not uncommon, and patients with higher exposure to GC and cyclophosphamide at baseline, and lower IgG levels are more likely to develop the disease
.
At the same time, in RTX therapy, the combination of hormones, pulmonary comorbidities, and diabetes may also be driving factors for patients with concurrent infections
.
In addition, during RTX induction and maintenance therapy, all patients should pay attention to the prevention of pneumocystis disease and actively receive influenza vaccine and pneumonia vaccine
.
RTX treatment may be a risk factor for the poor prognosis of patients with new coronavirus infection
.
Therefore, if the condition permits, AAV patients should be vaccinated before starting RTX therapy
.
Infusion reaction RTX treatment, the incidence of infusion reaction is low (5%), only a few reports of death due to infusion reaction, usually mild to moderate reaction
.
The most common manifestations are fever, rash, itching, and headache.
More serious manifestations include angioedema, hypotension, and bronchospasm
.
In addition to infection and infusion reactions, other adverse reactions, patients can also experience neutropenia after 6 to 8 months of RTX treatment, and usually recover on their own without treatment
.
Studies have shown that age, maleness, GPA subtype and cyclophosphamide treatment are related to the risk of malignant tumors in patients with AAV
.
Compared with the general population, RTX treatment of AAV patients has nothing to do with the increased risk of malignant tumors
.
In summary, rituximab can effectively treat AAV, and its remission induction effect is not inferior to cyclophosphamide.
Although it has side effects such as infection and infusion reactions, it has the advantages of not increasing the risk of malignant tumors, and overall Security is good
.
The maintenance treatment of rituximab can effectively reduce the recurrence rate, and the curative effect is better than that of azathioprine
.
However, the optimal duration of maintenance treatment needs to be further studied
.
References: Treppo E, Binutti M, Agarinis R, et al.
Rituximab Induction and Maintenance in ANCA-Associated Vasculitis: State of the Art and Future Perspectives.
J Clin Med.
2021 Aug 24;10(17):3773.
.
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of rare autoimmune diseases characterized by inflammation of the blood vessel wall, including granulomatous polyangiitis (GPA) and microscopic polyangiitis (MPA) and eosinophilic granulomatous polyangiitis (EGPA)
.
In 2021, the AAV management guidelines jointly issued by the American College of Rheumatology (ACR) and the Vasculitis Foundation pointed out that for active severe AAV, rituximab can be used to induce remission treatment; severe GPA/MPA patients receive cyclophosphamide or After rituximab treatment has achieved remission, rituximab can be used for subsequent maintenance remission treatment; rituximab can also be used for the treatment of recurrent AAV
.
So, what is the "charm" of rituximab? Recently, the journal J Clin Med.
(impact factor 4.
241) released a review to summarize randomized controlled trials of rituximab (RTX) in the treatment of AAV, and summarize its efficacy and safety in AAV induction and maintenance therapy
.
Rituximab can effectively induce remission, not inferior to cyclophosphamide.
In 2011, the U.
S.
Food and Drug Administration (FDA) approved RTX (375 mg/m2/w, intravenous injection, for 4 consecutive weeks) combined with glucocorticoid ( GC) Treatment of GPA/MPA
.
The approval is based on two random trials, RAVE and RITUXVAS
.
Studies have shown that in patients with new-onset and relapsed GPA/MPA, the efficacy of RTX to induce remission is not inferior to cyclophosphamide
.
The RAVE study included 197 patients with GPA/MPA and compared the efficacy of 375 mg/m2/w RTX and oral cyclophosphamide (2 mg/kg/d) for 4 weeks to induce remission
.
The data show that there is no significant difference in the efficacy of the two
.
The RITUXVAS study included 44 newly diagnosed GPA/MPA patients with renal impairment.
The results also showed that there was no significant difference in the efficacy of RTX and cyclophosphamide in inducing remission
.
It should be noted that none of the published RTX-related studies included patients with EGPA
.
According to the recently released systematic review of RTX treatment of EGPA, in both new-onset and recurrent EGPA patients, RTX induction therapy is effective, and patients with ANCA-positive EGPA may benefit more
.
However, more randomized controlled studies are needed to confirm the efficacy of RTX in the treatment of EGPA
.
Rituximab can effectively maintain remission and has better efficacy than azathioprine.
In addition, RTX is also recommended for maintaining remission in patients with GPA and MPA
.
Researches related to RTX maintenance treatment include MAINRITSAN, RITAZAREM, MAINRITSAN2, MAINRITSAN3
.
The MAINRITSAN study enrolled 115 AAV patients.
All patients received RTX or azathioprine maintenance therapy after treatment with hormones combined with cyclophosphamide to achieve remission
.
The results showed that during the 60-month follow-up, the RTX regimen was superior to azathioprine (AZA) in preventing recurrence
.
The RITAZAREM study included patients with relapsed AAV, and all patients received RTX combined with GC induction therapy
.
After achieving remission, the patient received maintenance therapy with RTX (1000 mg every 4 months for a total of 5 doses) or AZA (2 mg/kg/d)
.
The results show that RTX is better than AZA in preventing recurrence
.
The MAINRITSAN2 study shows that in addition to the 500mg/time dose, lower doses can also achieve the effect of maintaining remission
.
The MAINRITSAN3 study shows that after 18 months of maintenance treatment, extending the RTX treatment time (500 mg injection every 6 months for another 18 months) can effectively maintain remission and reduce recurrence
.
Rituximab has good safety in the treatment of AAV.
With the improvement of the prognosis of AAV patients, the safety of long-term treatment is increasingly valued
.
In the treatment of RTX, infection and infusion reactions are the most common adverse events
.
Infections associated with RTX therapy may be related to secondary hypogammaglobulinemia
.
Among AAV patients treated with RTX, hypogammaglobulinemia is not uncommon, and patients with higher exposure to GC and cyclophosphamide at baseline, and lower IgG levels are more likely to develop the disease
.
At the same time, in RTX therapy, the combination of hormones, pulmonary comorbidities, and diabetes may also be driving factors for patients with concurrent infections
.
In addition, during RTX induction and maintenance therapy, all patients should pay attention to the prevention of pneumocystis disease and actively receive influenza vaccine and pneumonia vaccine
.
RTX treatment may be a risk factor for the poor prognosis of patients with new coronavirus infection
.
Therefore, if the condition permits, AAV patients should be vaccinated before starting RTX therapy
.
Infusion reaction RTX treatment, the incidence of infusion reaction is low (5%), only a few reports of death due to infusion reaction, usually mild to moderate reaction
.
The most common manifestations are fever, rash, itching, and headache.
More serious manifestations include angioedema, hypotension, and bronchospasm
.
In addition to infection and infusion reactions, other adverse reactions, patients can also experience neutropenia after 6 to 8 months of RTX treatment, and usually recover on their own without treatment
.
Studies have shown that age, maleness, GPA subtype and cyclophosphamide treatment are related to the risk of malignant tumors in patients with AAV
.
Compared with the general population, RTX treatment of AAV patients has nothing to do with the increased risk of malignant tumors
.
In summary, rituximab can effectively treat AAV, and its remission induction effect is not inferior to cyclophosphamide.
Although it has side effects such as infection and infusion reactions, it has the advantages of not increasing the risk of malignant tumors, and overall Security is good
.
The maintenance treatment of rituximab can effectively reduce the recurrence rate, and the curative effect is better than that of azathioprine
.
However, the optimal duration of maintenance treatment needs to be further studied
.
References: Treppo E, Binutti M, Agarinis R, et al.
Rituximab Induction and Maintenance in ANCA-Associated Vasculitis: State of the Art and Future Perspectives.
J Clin Med.
2021 Aug 24;10(17):3773.
