Author suggestions for pathways to address unmet needs in CPPD clinical phenotyping and stratified medicine, and treatment: CPPD clinical phenotyping and stratified medicine
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Clinical CPPD phenotyping and natural disease course studies that include:
Large, multi-center studies, based in the community at large, and diverse consortia Longitudinally studying asymptomatic CC at baseline Better defining clinical phenotypes in chronic CPPD inflammatory polyarthritis, including host inflammatory response factors and qualitative and quantitative aspects of CPP crystal deposition
Better defining the complex relationship between OA and CPPD, and using longitudinal studies and diverse consortia Thoroughly defining clinical settings in which articular CPPD does substantial harm
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CPPD treatment:
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Limiting and reversing CPP crystal deposition (eg, by modulation of PPi metabolism, and potentially certain solutes, chondrocyte growth factors, and calciotropic and extracellular matrix factors)
In developing and testing such therapeutics:
Advance and validate testing for systemic and articular PPi metabolism at the clinical laboratory level to promote precision medicine Assess for possible limiting toxicity in bone and arteries of systemic PPi lowering Include study of intra-articular approaches
Strategies for testing existing and emerging anti-inflammatory drugs in acute CPP crystal arthritis should be adapted to distinct clinical features of CPPD (eg, frequent large joint acute arthritis, and chronic symmetric synovitis) Test emerging approaches effective in experimental crystal-induced inflammation (eg, NLRP3 inflammasome inhibitors) Design CPPD therapy trials to overcome natural limitations in recruitment and to select appropriate active comparator
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