title: Serum C-Reactive Protein as a Prognostic Biomarker in Amyotrophic Lateral Sclerosis.
abstract: Various factors have been proposed as possible candidates associated with the prognosis of amyotrophic lateral sclerosis (ALS); however, there is still no consensus on which biomarkers are reliable prognostic factors. C-reactive protein (CRP) is a biomarker of the inflammatory response that shows significant prognostic value for several diseases.
  
  
  
  To examine the prognostic significance of CRP in ALS.
  
  
  
  Patients' serum CRP levels were evaluated from January 1, 2009, to June 30, 2015, in a large cohort of patients with ALS observed by an Italian tertiary multidisciplinary center. Results were replicated in an independent cohort obtained from a population-based registry of patients with ALS. A post hoc analysis was performed of the phase 2 trial of NP001 to determine whether stratification by levels of CRP improves differentiation of responders and nonresponders to the drug.
  
  
  
  Serum CRP levels from the first examination were recorded to assess their effect on disease progression and survival.
  
  
  
  A total of 394 patients with ALS (168 women and 226 men; mean [SD] age at diagnosis, 60.18 [13.60] years) were observed in a tertiary multidisciplinary center, and the analysis was replicated in an independent cohort of 116 patients with ALS (50 women and 66 men; mean [SD] age at diagnosis, 67.00 [10.74] years) identified through a regional population-based registry. Serum CRP levels in the 394 patients with ALS correlated with severity of functional impairment, as measured by total score on the ALS Functional Rating Scale-Revised, at first evaluation (r = -0.14818; P = .004), and with patient survival (hazard ratio, 1.129; 95% CI, 1.033-1.234; P = .007). Similar results were found in the independent cohort (hazard ratio, 1.044; 95% CI, 1.016-1.056; P ≤ .001). Moreover, a post hoc analysis of the phase 2 trial of NP001 using the same CRP threshold showed that patients with elevated baseline CRP levels receiving the higher dose of NP001 had significantly less functional impairment after the treatment period compared with patients with normal baseline CRP, regardless of whether patients with normal CRP levels received NP001 or placebo (3.00 [3.62] vs -7.31 [6.23]; P = .04).
  
  
  
  These findings suggest that patients with ALS and elevated serum CRP levels progress more rapidly than do those with lower CRP levels and that this elevation may reflect a neuroinflammatory state potentially responsive to the immune regulators such as NP001.
authors.affiliation: NeuroMuscular Omnicentre, Fondazione Serena Onlus, Milano, Italy.
authors.forename: Christian
authors.initials: C
authors.lastname: Lunetta
authors.affiliation: NeuroMuscular Omnicentre, Fondazione Serena Onlus, Milano, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Lizio
authors.affiliation: NeuroMuscular Omnicentre, Fondazione Serena Onlus, Milano, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Maestri
authors.affiliation: NeuroMuscular Omnicentre, Fondazione Serena Onlus, Milano, Italy2Department of Biomedical Sciences for Health, University of Milan, Milan, Italy.
authors.forename: Valeria Ada
authors.initials: VA
authors.lastname: Sansone
authors.affiliation: Department of Neurological Rehabilitation, Fondazione Salvatore Maugeri, Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Scientifico di Milano, Milano, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Mora
authors.affiliation: Forbes Norris MDA/ALS Research and Treatment Center, California Pacific Medical Center, San Francisco, California.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Miller
authors.affiliation: Peggy and Gary Edwards ALS Laboratory, Department of Neurology, Houston Methodist Neurological Institute, Houston, Texas6Houston Methodist Research Institute, Houston, Texas7Department of Neurology, Methodist Neurological Institute, Houston Methodist Hospital, Houston, Texas.
authors.forename: Stanley H
authors.initials: SH
authors.lastname: Appel
authors.affiliation: Amyotrophic Lateral Sclerosis Center, "Rita Levi Montalcini" Department of Neuroscience, Neurology II, University of Torino, Turin, Italy9Azienda Ospedaliero-Universitaria Città della Salute e della Scienza, Torino, Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Chiò
mesh_terms: D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood* / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D012042:Registries
chemical_list: D015415:Biomarkers; D007155:Immunologic Factors; D002097:C-Reactive Protein