Background: Granulomatosis with Polyangiitis is a necrotizing vasculitis which affect small vessels resulting in a wide variety of symptoms commonly affecting the respiratory and kidney system. In patients who present with organ or life-threatening disease, it is recommended to start induction therapy with steroids and either Cyclophosphamide or Rituximab. In recent years, clinicians have used the C5a receptor inhibitor Avacopan with the purpose of decreasing the number of steroids faster during this phase of treatment. It has been reported that this medication is generally well tolerated, and it supports remission without the need for prolonging the use of steroids unnecessarily.

Objectives: This observational, retrospective cohort study aims to explore the outcomes of patients with GPA during induction therapy with Rituximab, prednisone and Avacopan utilizing the TrinetX database which included s electronic health records from > 143 different global healthcare organizations.

Methods: This is an observational and retrospective study made using the Trinetx database which encompasses an extensive database with over 120 million patients across different countries. We aim to evaluate outcomes among two groups. We identified two groups: The first cohort was comprised of patients with GPA on Rituximab, Prednisone and Avacopan (152 patients) and a second cohort comprised of patients with GPA on Rituximab and prednisone but no avacopan (3767 patients). Propensity score matching between both groups was done considering demographics, comorbidities and baseline medications, then we proceeded to evaluate outcomes such as infections (including Hepatitis B and C, Pneumocystis, and Herpes Simplex), MACE Risk, DAH, Glomerulonephritis attributed to GPA, transaminitis and adrenal insufficiency within one year of the index event which matched the timing of initiating induction therapy. Patients with prior liver disease, kidney disease or Chronic Hepatitis were excluded from the cohort.

Results: After matching, it was noted that 154 patients from each group met the criteria for said study. In the case of transaminitis we found that the risk on each group was not statistically significant as less than 10 patients of each court matched the abnormalities (RR=1.06 [95% CI=0.457, 2.479]). Herpes Zoster infection was prevalent in the group not receiving Avacopan, however less than 10 patients presented with this problem (p=0.0012), whereas in the group receiving avacopan, there were no cases reported. DAH was also noted to be present on both groups, however in <10 patients each (RR=1.217 [95% CI=0.53, 2.798]). In both groups the risk for developing nephritic syndrome related to GPA was also present on <10 patients (RR=1.21 [95% CI=0.523, 2.795]). Herpes Simplex infections were present in <10 patients on the group receiving avacopan (p=0.0012) and no single case was noted on the group not receiving this drug. Tuberculosis of the lung appeared to be present in less than 10 cases on the group not receiving avacopan (p=0.0013). Pneumocystosis risk seemed to be more prominent in the group receiving avacopan, as less than 10 patients developed this outcome, but no cases were seen in the group not receiving this medication (p=0.0012). In addition, the risk for developing adrenal insufficiency did not appear to be significant in both groups (RR=1.007 [95% CI= 0.432, 2.348]). The risk for developing Diabetes on both groups was not significant either (RR= 1.112 [95% CI=0.482, 2.568]. MACE Risk did not appear to be significant on any of the groups (RR=1.029 [95% CI=(0.442, 2.395)]. No cases of hepatitis C or B were reported in any of the groups.

Conclusion: Despite being a new medication with reported side effects related to the liver, avacopan seems to be well tolerated, however some of the infections explored in this study seem to be more prevalent in the group receiving avacopan, however, it is unclear if this is the result of the medication itself or a confounding factor as the cohort is smaller than the group that was receiving just Rituximab and prednisone. Furthermore, it does not appear that the implementation of Avacopan decreases the toxicity resulting from steroids as neither of the groups reported a significant statistical difference when it came to some of the explored side effects in these. In addition, it does not appear that these medication impacts cardiovascular risk negatively as there was no increase on MACE risk for any of these patients, however, one of the major limitations is that this medication is meant to be used over the course of a year. It must be noted that there is a huge difference between the size of both cohorts, and this might result in different confounding biases that might not necessarily reflect the safety profile of one group over the other, also, the reported outcomes were only studied over the course of a year, it is unclear if these are representative on each group.

REFERENCES: NIL.

Acknowledgements: NIL.

Disclosure of Interests: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.