Journal Article

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

Taylor, J., Brachemi, S., Chakera, A., Jayne, David, Lanyon, P., Emmi, G., Brogan, P., Gohh, R., Burnier, M., Klein, A., Owens, C., Luqmani, R., Little, M., Kaname, S., Griffin, S., Sznajd, J., Langford, C., Pusey, C., Belilos, E., Haubitz, M., Chester Wasko, M., Gregersen, J., Brunetta, E., Tsai, Y., Chua, I., Obi, R., Pieruzzi, F., Au Peh, C., Haller, H., Collins, M., Westman, K., Grevbo, B., Rigothier, C., Fujimoto, S., Hagino, N., Rychlik, I., Noble, E., McLaren, J., Teng, Y., Floege, J., Hougardy, J., Suranyi, M., Tiliakos, A., Ihata, A., Clarkson, M., Dua, A., Merkel, Peter, Flossmann, O., Niles, J., Mehling, H., Moranne, O., Alberici, F., Lindner, T., Bergner, R., Burton, J., Klocke, R., Vielhauer, V., De Vita, S., Manenti, L., Atsumi, T., Salvarani, Carlo, Morinobu, A., Anton, J., Horak, P., Witzke, O., Barrio Lucia, V., Dieperink, H., Mudge, D., Iking-Konert, C., Kurasawa, T., Cooper, B., Saadoun, D., Silva, A., Vogt, B., Laurin, L., Jourde-Chiche, N., Gipson, P., Soveri, I., van Daele, P., Segarra, A., Svensson, M., Tesar, V., Makanjuola, D., Katagiri, A., Bruchfeld, A., Carlin; Y, J., Hugenberg, S., Krarup, E., Komatsuda, A., Sugiyama, E., Liang, P., Co

2024

Overview

ObjectivesTo evaluate the efficacy and safety of avacopan in the subgroup of patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis receiving background induction therapy with rituximab in the phase 3 ADVOCATE trial.MethodsKey efficacy outcomes were remission at week 26 and sustained remission at week 52. Additional outcomes included the Glucocorticoid Toxicity Index, estimated glomerular filtration rate, urinary albumin to creatinine ratio, health-related quality of life and safety.ResultsOf the 330 patients who received study medication, 214 (64.8%) received rituximab (once weekly for 4 weeks), with a mean age of 59.8 years; 163 (76.2%) had renal vasculitis and 125 (58.4%) were newly diagnosed. Remission at week 26 and sustained remission at week 52 were achieved by 83/107 (77.6%) and 76/107 (71.0%) patients in the avacopan group and 81/107 (75.7%) and 60/107 (56.1%) in the prednisone taper group, respectively. The relapse rate, recovery of renal function, speed of reduction in albuminuria and glucocorticoid toxicity favoured the avacopan group. Serious adverse events occurred in 34.6% and 39.3% of patients in the avacopan and prednisone taper groups, respectively.ConclusionsThese data suggest that in patients with ANCA-associated vasculitis receiving rituximab, efficacy of treatment with avacopan compared with a prednisone taper was similar at week 26 and greater at week 52, with a favourable safety profile. In addition, avacopan was associated with improved renal outcomes and lower glucocorticoid toxicity. These results demonstrate the efficacy and safety of avacopan in patients receiving background induction therapy with rituximab.Trial registration number NCT02994927.

• Publisher: BMJ Publishing Group Ltd and European League Against Rheumatism,Elsevier Limited,BMJ Publishing Group
• Subject: Aniline Compounds / Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis - drug therapy / Antibodies, Antineutrophil Cytoplasmic / Antineutrophil cytoplasmic antibodies / Autoantibodies / Creatinine / Drug dosages / Glomerular filtration rate / Glucocorticoids / Glucocorticoids - adverse effects / Granulomatosis with polyangiitis / Humans / Hypothesis testing / Immunosuppressive Agents - therapeutic use / Immunotherapy / Induction therapy / Kidney diseases / Middle Aged / Missing data / Monoclonal antibodies / Nipecotic Acids / Prednisone / Quality of Life / Questionnaires / Remission / Remission (Medicine) / Remission Induction / Renal function / Rituximab / Rituximab - adverse effects / Safety / Standard of care / Statistical analysis / Systemic vasculitis / Toxicity / Vasculitis