Objectives: To investigate survival of interleukin (IL)-1 inhibitors in monogenic autoinflammatory disorders (mAID) through drug retention rate (DRR) and identify potential predictive factors of drug survival from a real-life perspective. Patients and methods: Multicentre retrospective study analyzing patients affected by the most common mAID treated with anakinra or canakinumab. Survival curves were analyzed with the Kaplan-Meier method. Statistical analysis included a Cox-proportional hazard model to detect factors responsible for drug discontinuation. Results: Seventy-eight patients for a total of 102 treatment regimens were enrolled. The mean treatment duration was 29.59 months. The estimated DRR of IL-1 inhibitors at 12, 24, and 48 months of follow-up was 75.8%, 69.7% and 51.1%, respectively. Patients experiencing an adverse event had a significantly lower DRR (p = 0.019). In contrast, no significant differences were observed between biologic-naïve patients and those previously treated with biologic drugs (p = 0.985) Patients carrying high-penetrance mutations exhibited a significantly higher DRR compared with those with low-penetrance variants (p = 0.015). Adverse events were the only variable associated with a higher hazard of treatment withdrawal (HR 2.573 [CI: 1.223-5.411], p = 0.013) on regression analysis. A significant glucorticoid-sparing effect was observed (p < 0.0001). Conclusions: IL-1 inhibitors display an excellent long-term effectiveness in terms of DRR, and their survival is not influenced by the biologic line of treatment. They display a favorable safety profile, that deserves however a close monitoring given its impact on treatment continuation. Special attention should be paid to molecular diagnosis and mutation penetrance, as patients carrying low-penetrance variants are more likely to interrupt treatment.

Sota, J., Rigante, D., Cimaz, R., Cattalini, M., Frassi, M., Manna, R., Sicignano, L., Verrecchia, E., Aragona, E., Maggio, M., Lopalco, G., Emmi, G., Parronchi, P., Cauli, A., Wiesik-Szewczyk, E., Hernández-Rodríguez, J., Gaggiano, C., Tarsia, M., Mourabi, M., Ragab, G., Vitale, A., Fabiani, C., Frediani, B., Lamacchia, V., Renieri, A., Cantarini, L., Drug survival of anakinra and canakinumab in monogenic autoinflammatory diseases: observational study from the International AIDA Registry, <<RHEUMATOLOGY>>, 2021; 2021 (60): 5705-5712. [doi:10.1093/rheumatology/keab419] [http://hdl.handle.net/10807/190181]

Drug survival of anakinra and canakinumab in monogenic autoinflammatory diseases: observational study from the International AIDA Registry

Rigante, D;Manna, R;Sicignano, Ll;Verrecchia, E;
2021

Abstract

Objectives: To investigate survival of interleukin (IL)-1 inhibitors in monogenic autoinflammatory disorders (mAID) through drug retention rate (DRR) and identify potential predictive factors of drug survival from a real-life perspective. Patients and methods: Multicentre retrospective study analyzing patients affected by the most common mAID treated with anakinra or canakinumab. Survival curves were analyzed with the Kaplan-Meier method. Statistical analysis included a Cox-proportional hazard model to detect factors responsible for drug discontinuation. Results: Seventy-eight patients for a total of 102 treatment regimens were enrolled. The mean treatment duration was 29.59 months. The estimated DRR of IL-1 inhibitors at 12, 24, and 48 months of follow-up was 75.8%, 69.7% and 51.1%, respectively. Patients experiencing an adverse event had a significantly lower DRR (p = 0.019). In contrast, no significant differences were observed between biologic-naïve patients and those previously treated with biologic drugs (p = 0.985) Patients carrying high-penetrance mutations exhibited a significantly higher DRR compared with those with low-penetrance variants (p = 0.015). Adverse events were the only variable associated with a higher hazard of treatment withdrawal (HR 2.573 [CI: 1.223-5.411], p = 0.013) on regression analysis. A significant glucorticoid-sparing effect was observed (p < 0.0001). Conclusions: IL-1 inhibitors display an excellent long-term effectiveness in terms of DRR, and their survival is not influenced by the biologic line of treatment. They display a favorable safety profile, that deserves however a close monitoring given its impact on treatment continuation. Special attention should be paid to molecular diagnosis and mutation penetrance, as patients carrying low-penetrance variants are more likely to interrupt treatment.
Inglese
Sota, J., Rigante, D., Cimaz, R., Cattalini, M., Frassi, M., Manna, R., Sicignano, L., Verrecchia, E., Aragona, E., Maggio, M., Lopalco, G., Emmi, G., Parronchi, P., Cauli, A., Wiesik-Szewczyk, E., Hernández-Rodríguez, J., Gaggiano, C., Tarsia, M., Mourabi, M., Ragab, G., Vitale, A., Fabiani, C., Frediani, B., Lamacchia, V., Renieri, A., Cantarini, L., Drug survival of anakinra and canakinumab in monogenic autoinflammatory diseases: observational study from the International AIDA Registry, <<RHEUMATOLOGY>>, 2021; 2021 (60): 5705-5712. [doi:10.1093/rheumatology/keab419] [http://hdl.handle.net/10807/190181]
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