title: A Personalized Approach to Biological Therapy Using Prediction of Clinical Response Based on MRP8/14 Serum Complex Levels in Rheumatoid Arthritis Patients.
abstract: OBJECTIVE
  Measurement of MRP8/14 serum levels has shown potential in predicting clinical response to different biological agents in rheumatoid arthritis (RA). We aimed to develop a treatment algorithm based on a prediction score using MRP8/14 measurements and clinical parameters predictive for response to different biological agents.
  
  
  METHODS
  Baseline serum levels of MRP8/14 were measured in 170 patients starting treatment with infliximab, adalimumab or rituximab. We used logistic regression analysis to develop a predictive score for clinical response at 16 weeks. MRP8/14 levels along with clinical variables at baseline were investigated. We also investigated how the predictive effect of MRP8/14 was modified by drug type. A treatment algorithm was developed based on categorizing the expected response per drug type as high, intermediate or low for each patient and optimal treatment was defined. Finally, we present the utility of using this treatment algorithm in clinical practice.
  
  
  RESULTS
  The probability of response increased with higher baseline MRP8/14 complex levels (OR = 1.39), differentially between the TNF-blockers and rituximab (OR of interaction term = 0.78), and also increased with higher DAS28 at baseline (OR = 1.28). Rheumatoid factor positivity, functional disability (a higher HAQ), and previous use of a TNF-inhibitor decreased the probability of response. Based on the treatment algorithm 80 patients would have been recommended for anti-TNF treatment, 8 for rituximab, 13 for another biological treatment (other than TNFi or rituximab) and for 69 no recommendation was made. The predicted response rates matched the observed response in the cohort well. On group level the predicted response based on the algorithm resulted in a modest 10% higher response rate in our cohort with much higher differences in response probability in individual patients treated contrary to treatment recommendation.
  
  
  CONCLUSIONS
  Prediction of response using MRP8/14 levels along with clinical predictors has potential in personalizing treatment for RA patients starting biological anti-rheumatic treatment, and might increase cost-effectiveness.
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Center, Utrecht, The Netherlands.
authors.forename: S C
authors.initials: SC
authors.lastname: Nair
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Center, Utrecht, The Netherlands.
authors.forename: P M J
authors.initials: PM
authors.lastname: Welsing
authors.affiliation: Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: I Y K
authors.initials: IY
authors.lastname: Choi
authors.affiliation: Institute of Immunology, University Hospital Muenster, Muenster, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Roth
authors.affiliation: Department of Pediatric Rheumatology and Immunology, University Children's Hospital Muenster, Muenster, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Holzinger
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Center, Utrecht, The Netherlands.
authors.forename: J W J
authors.initials: JW
authors.lastname: Bijlsma
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Center, Utrecht, The Netherlands.
authors.forename: J M
authors.initials: JM
authors.lastname: van Laar
authors.affiliation: Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: D M
authors.initials: DM
authors.lastname: Gerlag
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Center, Utrecht, The Netherlands.
authors.forename: F P J G
authors.initials: FP
authors.lastname: Lafeber
authors.affiliation: Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: P P
authors.initials: PP
authors.lastname: Tak
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000097:blood*; D000068879:Adalimumab / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D040502:Calgranulin B / Q000097:blood*; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy; D000069285:Infliximab / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D057285:Precision Medicine; D000069283:Rituximab / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: C435500:ABCC11 protein, human; D018528:ATP-Binding Cassette Transporters; D018501:Antirheumatic Agents; D015415:Biomarkers; D040502:Calgranulin B; D000069283:Rituximab; D000069285:Infliximab; D000068879:Adalimumab