6533b828fe1ef96bd1288357
RESEARCH PRODUCT
Drug survival of anakinra and canakinumab in monogenic autoinflammatory diseases: observational study from the International AIDA Registry
Elena VerrecchiaVittoria LamacchiaMaria TarsiaJurgen SotaCarla GaggianoMariam MourabiLuca CantariniAntonio VitaleAlberto CauliGiacomo EmmiMaria Cristina MaggioGiuseppe LopalcoPaola ParronchiGaafar RagabMicol FrassiMarco CattaliniEmma AragonaJosé Hernández-rodríguezRolando CimazDonato RiganteBruno FredianiLudovico Luca SicignanoClaudia FabianiEwa Wiesik-szewczykRaffaele MannaAlessandra Renierisubject
Male0301 basic medicineTime FactorsSettore MED/16 - REUMATOLOGIAInterleukin-1beta0302 clinical medicineSettore MED/38 - Pediatria Generale E SpecialisticaMonoclonalPharmacology (medical)RegistriesHumanizedmedia_commonIL-1 anakinra canakinumab innovative biotechnologies monogenic autoinflammatory disorders personalized medicinepersonalized medicineMiddle AgedPenetranceTreatment OutcomeAnakinraAntirheumatic AgentsAutoinflammationIL-1; anakinra; canakinumab; innovative biotechnologies; monogenic autoinflammatory disorders; personalized medicine; Adult; Antibodies Monoclonal Humanized; Antirheumatic Agents; Female; Follow-Up Studies; Hereditary Autoinflammatory Diseases; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-1beta; Male; Middle Aged; Retrospective Studies; Time Factors; Treatment Outcome; Young Adult; RegistriesFemalemedicine.drugAdultDrugmedicine.medical_specialtymedia_common.quotation_subjectAntibodies Monoclonal HumanizedcanakinumabAntibodiesYoung Adult03 medical and health sciencesinnovative biotechnologiesRheumatologyInternal medicinemedicineHumansAdverse effectSurvival analysismonogenic autoinflammatory disordersRetrospective Studies030203 arthritis & rheumatologyAnakinraIL-1business.industryHereditary Autoinflammatory DiseasesRetrospective cohort studyInterleukin 1 Receptor Antagonist ProteinCanakinumab030104 developmental biologyObservational studybusinessFollow-Up Studiesdescription
Abstract Objectives To investigate survival of 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 analysing patients affected by the most common mAID treated with anakinra or canakinumab. Survival curves were analysed 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 [hazard ratio (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 favourable safety profile, which 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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2021-01-01 |