Treat-to-target strategies for the management of familial Mediterranean Fever in children

Abstract

Background The objective of this initiative was to develop a treat-to-target (T2T) approach for the management of patients with Familial Mediterranean Fever (FMF), including the definition of a complex treatment target, and establish strategies that improve patient care and long-term outcome. Methods An initial set of statements as well as a flow chart visualising the proposed concept was developed. To adapt the preliminary statements to the current state of knowledge, a systematic literature search was performed and the modified statements were subject to a Delphi approach. To ensure the applicability of the statements in daily practice, an online survey was conducted among paediatric rheumatologists in Germany. In addition, data from the national AID-NET registry were analysed with respect to therapeutic response. Results This T2T initiative yielded a total of 26 statements guiding FMF management with respect to diagnosis, treatment targets, treatment strategies and monitoring. The online survey identified cut-off values for inflammatory markers indicating treatment intensification and appropriate measures in case of colchicine intolerance or non-adherence. The analysis of data derived from the national AID-NET showed that colchicine therapy was successfully terminated in 61% of patients (27 out of 44) with heterozygous MEFV mutations. Multidimensional treatment targets incorporating objective and subjective reported outcome measures were developed. These provide the basis for stratifying patients into the following treatment paths: continue colchicine, persisting attacks / inflammation, colchicine intolerance, persisting arthritis, colchicine reduction and adjustment/reduction of biologics. Conclusions The proposed consensus treatment plan for the management of FMF incorporates multidimensional targets allowing transparent treatment decisions, which will promote personalised disease management and increase adherence to therapy.

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

“…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].…”

“…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]. Furthermore, it can avoid drug overexposure with increased risk of adverse events and higher drug costs than needed [43,[45][46][47][48].…”

“…This highlights the importance of clarity on measuring constructs of disease activity, disease damage, burden of illness, and objective assessment of fatigue/sleep quality [57]. Recently, the Protokolle in der Kinderrheumatologie (PRO-KIND) initiative of the German Society for Pediatric Rheumatology (GKJR) has proposed a new composite tool for FMF [17]. This multidimensional instrument combines the assessment of flare frequency, missed school/working days, inflammatory markers, chronic sequelae/disease damage, the PGA, and the PPGA [17].…”

“…Recently, T2T strategies for IL-1 AID were published [16][17][18]. However, longitudinal real-life data of disease activity-based treatment adjustments and their impact on IL-1 AID in childhood is scarce.…”

Usefulness of interleukin-1 blockade in autoinflammatory diseases

“…The ultimate goal of therapy in IL-1 driven autoinflammatory diseases is to gain control of symptoms, normalize systemic inflammation, and minimize or prevent the development of organ damage. A treat-to-target (T2T) approach which could enable individualization of therapy has not been published by leading international societies except for familial Mediterranean fever [ 7 , 8 ]. We lack sufficient evidence obtained by controlled trials of the efficacy of anti-IL-1 agents in preventing amyloidosis or their safety in pregnancy [ 4 , 9 ].…”