A Personalized Approach to Biological Therapy Using Prediction of Clinical Response Based on MRP8/14 Serum Complex Levels in Rheumatoid Arthritis Patients

• Published in: PloS one Vol. 11; no. 3; p. e0152362
• Main Authors: Nair, S C, Welsing, P M J, Choi, I Y K, Roth, J, Holzinger, D, Bijlsma, J W J, van Laar, J M, Gerlag, D M, Lafeber, F P J G, Tak, P P
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30.03.2016; Public Library of Science (PLoS)
• Subjects: Adalimumab - therapeutic use; Adult; Aged; Algorithms; Antiarthritic agents; Antirheumatic Agents - therapeutic use; Arthritis; Arthritis, Rheumatoid - blood; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - immunology; ATP-Binding Cassette Transporters - blood; Biological effects; Biological products; Biological treatment; Biology and Life Sciences; Biomarkers; Biomarkers - blood; Calgranulin B - blood; Care and treatment; Clinical medicine; Evaluation; Female; Health risk assessment; Humans; Immunoglobulins; Immunology; Immunosuppression; Immunotherapy; Inflammation; Infliximab; Infliximab - therapeutic use; Male; Medicine and Health Sciences; Middle Aged; Monoclonal antibodies; Patient outcomes; Patients; Physical Sciences; Precision Medicine; Predictions; Proteins; Regression analysis; Research and Analysis Methods; Rheumatic diseases; Rheumatism; Rheumatoid arthritis; Rheumatoid factor; Rheumatology; Rituximab; Rituximab - therapeutic use; Serum levels; Statistical analysis; Targeted cancer therapy; TNF inhibitors; Treatment Outcome; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0152362

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. 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. 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. 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.