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A highlight from the LUPUS 2014 meeting: eight great ideas.

Buyon JP, Cohen P, Merrill JT, Gilkeson G, Kaplan M, James J, McCune WJ, Bernatsky S, Elkon K - Lupus Sci Med (2015)

Bottom Line: This review describes eight 'great ideas' regarding bench-to-bedside considerations in systemic lupus erythematosus (SLE) presented at the second international LUPUS meeting in Quebec, September 2014.The topics included: correcting the impaired clearance of apoptotic fragments; optimisation of clinical trial design: the PERFECT (Pre Evaluation Reducing Frighteningly Elevated Coverable Targets) study; lipidomics and metabolomics in SLE; importance of the inflammasome; identification and treatment of asymptomatic autoimmunity: prevention of SLE; combining low doses of hydroxychloroquine and quinacrine for long-term maintenance therapy of SLE; reducing emergency room visits and the critical relevance of the autoantigen.

View Article: PubMed Central - PubMed

Affiliation: Division of Rheumatology, Department of Medicine , NYU School of Medicine , New York, New York , USA.

ABSTRACT
This review describes eight 'great ideas' regarding bench-to-bedside considerations in systemic lupus erythematosus (SLE) presented at the second international LUPUS meeting in Quebec, September 2014. The topics included: correcting the impaired clearance of apoptotic fragments; optimisation of clinical trial design: the PERFECT (Pre Evaluation Reducing Frighteningly Elevated Coverable Targets) study; lipidomics and metabolomics in SLE; importance of the inflammasome; identification and treatment of asymptomatic autoimmunity: prevention of SLE; combining low doses of hydroxychloroquine and quinacrine for long-term maintenance therapy of SLE; reducing emergency room visits and the critical relevance of the autoantigen.

No MeSH data available.


Related in: MedlinePlus

Proposal for the PERFECT Trial.
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LUPUS2015000087F1: Proposal for the PERFECT Trial.

Mentions: JPB submitted that there are many great ideas in thinking about SLE, but no great idea will fit all SLE—because SLE is heterogeneous. Perhaps the greatest idea is to simply acknowledge this fact, and accept its profound consequences for the pharmaceutical industry, that one targeted treatment will not work optimally for all patients, one dose will not work for even all of the appropriate patients and some patients may require addressing more than one immunological pathway. To address this (perhaps obvious but nevertheless iconoclastic notion may not be entirely congruent with Federal Drug Administration (FDA) guidelines for treatment development—http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm072063.pdf), JPB partnered with JTM and proposed a trial design which considers individuality by focusing on clinical activity that is accompanied by activation of a treatment-specific, pharmacodynamic target. The PERFECT (Pre Evaluation Reducing Frighteningly Elevated Coverable Targets) trial begins with an open–label, dose escalation study in patients known to have dysregulation in a pathway targeted by a given biologic to initially determine the optimal dose for target coverage. This achieves two goals: it assures a reduction in the desired target has been made at an optimal dose for each patient (ideally total reduction but acknowledging 50% might be acceptable if that is the ceiling using the highest safely tolerated dose), and eliminates patients who have <50% reduction since the drug is not likely to have benefit. Those achieving target reduction are then blindly randomised to remain on their optimal dose or be withdrawn with the primary endpoint being evaluation of flares (summarised in figure 1). For patients who achieve target coverage but who don't have a clinical response, exploration of additional active pathways or immunological feedback loops in response to the therapy might suggest logical combination treatments for these individuals.


A highlight from the LUPUS 2014 meeting: eight great ideas.

Buyon JP, Cohen P, Merrill JT, Gilkeson G, Kaplan M, James J, McCune WJ, Bernatsky S, Elkon K - Lupus Sci Med (2015)

Proposal for the PERFECT Trial.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493165&req=5

LUPUS2015000087F1: Proposal for the PERFECT Trial.
Mentions: JPB submitted that there are many great ideas in thinking about SLE, but no great idea will fit all SLE—because SLE is heterogeneous. Perhaps the greatest idea is to simply acknowledge this fact, and accept its profound consequences for the pharmaceutical industry, that one targeted treatment will not work optimally for all patients, one dose will not work for even all of the appropriate patients and some patients may require addressing more than one immunological pathway. To address this (perhaps obvious but nevertheless iconoclastic notion may not be entirely congruent with Federal Drug Administration (FDA) guidelines for treatment development—http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm072063.pdf), JPB partnered with JTM and proposed a trial design which considers individuality by focusing on clinical activity that is accompanied by activation of a treatment-specific, pharmacodynamic target. The PERFECT (Pre Evaluation Reducing Frighteningly Elevated Coverable Targets) trial begins with an open–label, dose escalation study in patients known to have dysregulation in a pathway targeted by a given biologic to initially determine the optimal dose for target coverage. This achieves two goals: it assures a reduction in the desired target has been made at an optimal dose for each patient (ideally total reduction but acknowledging 50% might be acceptable if that is the ceiling using the highest safely tolerated dose), and eliminates patients who have <50% reduction since the drug is not likely to have benefit. Those achieving target reduction are then blindly randomised to remain on their optimal dose or be withdrawn with the primary endpoint being evaluation of flares (summarised in figure 1). For patients who achieve target coverage but who don't have a clinical response, exploration of additional active pathways or immunological feedback loops in response to the therapy might suggest logical combination treatments for these individuals.

Bottom Line: This review describes eight 'great ideas' regarding bench-to-bedside considerations in systemic lupus erythematosus (SLE) presented at the second international LUPUS meeting in Quebec, September 2014.The topics included: correcting the impaired clearance of apoptotic fragments; optimisation of clinical trial design: the PERFECT (Pre Evaluation Reducing Frighteningly Elevated Coverable Targets) study; lipidomics and metabolomics in SLE; importance of the inflammasome; identification and treatment of asymptomatic autoimmunity: prevention of SLE; combining low doses of hydroxychloroquine and quinacrine for long-term maintenance therapy of SLE; reducing emergency room visits and the critical relevance of the autoantigen.

View Article: PubMed Central - PubMed

Affiliation: Division of Rheumatology, Department of Medicine , NYU School of Medicine , New York, New York , USA.

ABSTRACT
This review describes eight 'great ideas' regarding bench-to-bedside considerations in systemic lupus erythematosus (SLE) presented at the second international LUPUS meeting in Quebec, September 2014. The topics included: correcting the impaired clearance of apoptotic fragments; optimisation of clinical trial design: the PERFECT (Pre Evaluation Reducing Frighteningly Elevated Coverable Targets) study; lipidomics and metabolomics in SLE; importance of the inflammasome; identification and treatment of asymptomatic autoimmunity: prevention of SLE; combining low doses of hydroxychloroquine and quinacrine for long-term maintenance therapy of SLE; reducing emergency room visits and the critical relevance of the autoantigen.

No MeSH data available.


Related in: MedlinePlus