Tapering of biological treatment in autoinflammatory diseases: a scoping review

Abstract

Background Biological treatment and treat-to-target approaches guide the achievement of inactive disease and clinical remission in Autoinflammatory Diseases (AID). However, there is limited evidence addressing optimal tapering strategies and/or discontinuation of biological treatment in AID. This study evaluates available evidence of tapering biological treatment and explores key factors for successful tapering. Methods A systematic literature search was conducted in Embase, MEDLINE, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials using the OVID platform (1990-08/2020). Bibliographic search of relevant reviews was also performed. Studies/case series (n ≥ 5) in AID patients aged ≤ 18 years with biological treatment providing information on tapering/treatment discontinuation were included. After quality assessment aggregated data were extracted and synthesized. Tapering strategies were explored. Results A total of 6035 records were identified. Four papers were deemed high quality, all focused on systemic juvenile idiopathic arthritis (sJIA) (1 open-label randomized trial, 2 prospective, 1 retrospective observational study). Biological treatment included anakinra (n = 2), canakinumab (n = 1) and tocilizumab (n = 1). Strategies in anakinra tapering included alternate-day regimen. Canakinumab tapering was performed randomized for dose reduction or interval prolongation, whereas tocilizumab was tapered by interval prolongation. Key factors identified included early start of biological treatment and sustained inactive disease. Conclusion Tapering of biological treatment after sustained inactive disease should be considered. Guidance for optimal strategies is limited. Future studies may leverage therapeutic drug monitoring in combination with pharmacometric modelling to further enhance personalized “taper-to-target” strategies respecting individual patients and diseases aspects.

Optimized Treatment of Interleukin (IL-1)-Mediated Autoinflammatory Diseases: Impact of Disease Activity-Based Treatment Adjustments

“…Disease activity-based treatment adjustments can improve the outcome of patients with IL-1 AID including achieving remission/mild disease activity, improving HrQoL, and reducing the risk of organ damage. A rationale for disease activity-based treatment adjustments is the interplay of patient-related (e.g., age, living circumstances), diseaserelated (e.g., genotype, organ damage), and treatment-related (e.g., pharmacokinetics, side effects) factors [28][29][30]. The integration of these factors results in individual disease activity trajectories, as demonstrated in this study.…”

“…Based on the drug exposure-response relationship in IL-1 AID, T2T strategies can help to avoid drug underexposure and associated treatment failure. Additionally, they may guide treatment tapering decisions [17,28,42,43]. Individualized disease activity-based treatments and the application of T2T recommendations in IL-1 AID can, therefore, reduce the risk of suboptimal disease management, associated morbidity, and long-term organ damage [10,16,17,44].…”

Exploring the Landscape of Anti-Inflammatory Trials: A Comprehensive Review of Strategies for Targeting Inflammation in Acute Myocardial Infraction

“…Canakinumab, an interleukin-1 beta (IL-1β) inhibitor, was approved for use in several rare, heritable pediatric conditions associated with IL-1β over-expression [ 28 ]. The CANTOS trial examined the efficacy of canakinumab in reducing the CV events among 10,061 patients with a history of MI and elevated high-sensitivity C-reactive proteins (hsCRPs).…”

Exploring the Landscape of Anti-Inflammatory Trials: A Comprehensive Review of Strategies for Targeting Inflammation in Acute Myocardial Infraction

“…Canakinumab, an interleukin-1 beta (IL-1β) inhibitor, was approved for use in several rare, heritable pediatric conditions associated with IL-1β over-expression [28]. The CAN-TOS trial examined the efficacy of canakinumab in reducing the CV events among 10,061 patients with a history of MI and elevated high-sensitivity C-reactive proteins (hsCRPs).…”