Recommendations for the management of autoinflammatory diseases

Haar, Nienke Ter; Oswald, Marlen; Jeyaratnam, Jerold; Antón, Jordi; Barron, KS; Brogan, Paul A.; Cantarini, Luca; Galeotti, Caroline; Grateau, Gilles; Hentgen, Véronique; Hofer, Michaël; Kallinich, Tilmann; Koné‐Paut, Isabelle; Lachmann, HJ; Özdoğan, Huri; Özen, Seza; Russo, Ricardo; Simon, Anna; Uziel, Yosef; Wouters, Carine; Feldman, Brian M.; Vastert, Bas; Wulffraat, NM; Benseler, Susanne M.; Frenkel, Joost; Gattorno, Marco; Kuemmerle‐Deschner, J. B.

doi:10.1186/1546-0096-13-s1-p133

Cited by 17 publications

(24 citation statements)

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“…Availability of national referral guidelines and clinical recommendations for PRD was surprisingly low both in WEC and EEC. This important unmet need is currently being addressed by another work package of the SHARE project, with several sets of recommendations and clinical guidelines now published for various PRD (14)(15)(16), as several others pending publication. In 15 countries there were differing replies from individual centres within one country to the question on the existence of an "official system of national referral centres".…”

Section: Discussionmentioning

confidence: 99%

The European network for care of children with paediatric rheumatic diseases: care across borders

et al. 2019

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Objectives: To provide an overview of the paediatric rheumatology (PR) care in Europe to inform future specialist service provision. Methods: An online survey was developed and presented to national coordinating centres of the Pediatric Rheumatology International Trials Organisation (PRINTO) representing a single EU member state (35 centres; Country survey); and to 288 individual PR centres (Centre and Disease Surveys) as a part of the EU project SHARE. The survey contained country and centre specific components covering organisation of PR care, composition of teams, education, healthcare and research facilities, and assessment of needs. The national coordinating centres completed both centre as well as country questions. Results: Response rates were 83% for Country and 57% for Centre surveys. Data from both surveys were itemised to organisational, quality of care and educational aspects. Across the EU, only one paediatric rheumatologist is available per million population, located in one of the 288 centres with specialised PR care. In all EU member states, there is overall good access to specialist care and to approved medications, although off-label medication availability is worse in Eastern European countries. Full financial coverage is provided for most prescribed medications. PR education is widely available for physicians but is insufficient for allied health professionals. Participation in clinical trials is generally high. Among important gaps identified, lack of widely accepted clinical guidelines/recommendations; and insufficient adolescent transition management planning were highlighted. Conclusions: This study provides a comprehensive analysis of specialist PR service provision across Europe. Seen from the perspective of health care providers, there are no major differences between EU member states. Rarity, chronicity and complexity of diseases form a major challenge to paediatric rheumatology care. Therefore, strengthening subspecialty networks (Paediatric Rheumatology European Society, PReS, PRINTO, and SHARE) and the recently created European Reference Networks (ERN) will facilitate provision an dissemination of standards of care and treatment recommendations to further improve patient-centred healthcare across Europe.

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Section: Discussionmentioning

confidence: 99%

The European network for care of children with paediatric rheumatic diseases: care across borders

et al. 2019

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“…Current therapies include corticosteroids with significant side-effects when used long-term, and expensive biologics that neutralize cytokines produced as a consequence of the disease mechanisms, rather than targeting the underlying aetiology [12,27]. To address this, we developed, optimized and validated a protein microarray-based network pharmacology approach to identify repurposing drugs that simultaneously target multiple signaling pathways that are activated in TRAPS.…”

Section: Discussionmentioning

confidence: 99%

“…Current treatment options for TRAPS include corticosteroids (with potentially major side-effects) and cytokine-blocking biologics; although the latter represent a major advance in the management of TRAPS, they are expensive, may require specialist administration, and show variable, unpredictable, limited efficacy [12,13].…”

Section: Introductionmentioning

confidence: 99%

A signalome screening approach in the autoinflammatory disease TNF receptor associated periodic syndrome (TRAPS) highlights the anti-inflammatory properties of drugs for repurposing

Todd

Negm

Reps

et al. 2017

Pharmacological Research

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2Abbreviations: BCA, bicinchoninic acid; CV, coefficient of variation; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; PBMCs, peripheral blood mononuclear cells; RPPA, reverse phase protein array; SSMD, strictly standardised mean difference; TNFR1, tumour necrosis factor receptor-1; TRAPS, TNF receptor associated periodic syndrome; WT, wild type. 3ABSTRACT: TNF Receptor Associated Periodic Syndrome (TRAPS) is an autoinflammatory disease caused by mutations in TNF Receptor 1 (TNFR1). Current therapies for TRAPS are limited and do not target the pro-inflammatory signalling pathways that are central to the disease mechanism. Our aim was to identify drugs for repurposing as anti-inflammatories based on their ability to down-regulate molecules associated with inflammatory signalling pathways that are activated in TRAPS. This was achieved using rigorously optimised, high through-put cell culture and reverse phase protein microarray systems to screen compounds for their effects on the TRAPS-associated inflammatory signalome. 1360 approved, publically available, pharmacologically active substances were investigated for their effects on 40 signalling molecules associated with pro-inflammatory signalling pathways that are constitutively upregulated in TRAPS. The drugs were screened at four ten-fold concentrations on cell lines expressing both wild-type (WT) TNFR1 and TRAPS-associated C33Y mutant TNFR1, or WT TNFR1 alone; signalling molecule levels were then determined in cell lysates by the reversephase protein microarray. A novel mathematical methodology was developed to rank the compounds for their ability to reduce the expression of signalling molecules in the C33Y-TNFR1 transfectants towards the level seen in the WT-TNFR1 transfectants. Seven high-ranking drugs were selected and tested by RPPA for effects on the same 40 signalling molecules in lysates of peripheral blood mononuclear cells (PBMCs) from C33Y-TRAPS patients compared to PBMCs from normal controls. The fluoroquinolone antibiotic lomefloxacin, as well as others from this class of compounds, showed the most significant effects on multiple pro-inflammatory signalling pathways that are constitutively activated in TRAPS; lomefloxacin dose-dependently significantly reduced expression of 7/40 signalling molecules across the Jak/Stat, MAPK, NF-kB and PI3K/AKT pathways. This study demonstrates the power of signalome screening for identifying candidates for drug repurposing.

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“…Members of the PRO-KIND working group have previously led (JKD) or participated (SMB) in the Europe-wide SHARE initiative and developed evidence-based recommendations for the diagnosis and management of autoinflammatory diseases [19]. These had synthesized the published evidence until June 2013.…”

Section: Evidence Synthesis Context Adaptation and Statement Developmentioning

confidence: 99%

“…In 2015, the Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) initiative set out to improve the management of patients with rheumatic diseases including AIDs [19]. SHARE investigators synthesized the published evidence and developed management recommendations.…”

Section: Introductionmentioning

confidence: 99%

Consensus protocols for the diagnosis and management of the hereditary autoinflammatory syndromes CAPS, TRAPS and MKD/HIDS: a German PRO-KIND initiative

et al. 2020

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Background: Rare autoinflammatory diseases (AIDs) including Cryopyrin-Associated Periodic Syndrome (CAPS), Tumor Necrosis Receptor-Associated Periodic Syndrome (TRAPS) and Mevalonate Kinase Deficiency Syndrome (MKD)/ Hyper-IgD Syndrome (HIDS) are genetically defined and characterized by recurrent fever episodes and inflammatory organ manifestations. Early diagnosis and early start of effective therapies control the inflammation and prevent organ damage. The PRO-KIND initiative of the German Society of Pediatric Rheumatology (GKJR) aims to harmonize the diagnosis and management of children with rheumatic diseases nationally. The task of the PRO-KIND CAPS/TRAPS/MKD/HIDS working group was to develop evidence-based, consensus diagnosis and management protocols including the first AID treat-to-target strategies. Methods: The national CAPS/TRAPS/MKD/HIDS expert working group was established, defined its aims and conducted a comprehensive literature review synthesising the recent (2013 to 2018) published evidence including all available recommendations for diagnosis and management. General and disease-specific statements were anchored in the 2015 SHARE recommendations. An iterative expert review process discussed, adapted and refined these statements. Ultimately the GKJR membership vetted the proposed consensus statements, agreement of 80% was mandatory for inclusion. The approved statements were integrated into three disease specific consensus treatment plans (CTPs). These were developed to enable the implementation of evidence-based, standardized care into clinical practice.

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Recommendations for the management of autoinflammatory diseases

Cited by 17 publications

References 0 publications

The European network for care of children with paediatric rheumatic diseases: care across borders

The European network for care of children with paediatric rheumatic diseases: care across borders

A signalome screening approach in the autoinflammatory disease TNF receptor associated periodic syndrome (TRAPS) highlights the anti-inflammatory properties of drugs for repurposing

Consensus protocols for the diagnosis and management of the hereditary autoinflammatory syndromes CAPS, TRAPS and MKD/HIDS: a German PRO-KIND initiative

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