BACKGROUND: The performance of a clinical pharmacogenetic model to predict nonresponse of methotrexate (MTX) monotherapy in patients with established rheumatoid arthritis (RA) and failure of disease-modifying antirheumatic drugs (DMARDs) was studied. METHODS: For 75 RA patients receiving MTX monotherapy for 6 months, DNA and clinical data were available. Risk scores for nonresponse at 6 months (disease activity score >2.4), were calculated using the pharmacogenetic prediction model utilizing four clinical factors and four polymorphisms in the genes MTHFD1, AMPD1, ITPA and ATIC. RESULTS: At 6 months, there were 25 responders and 50 nonresponders. Using the clinical pharmacogenetic prediction model, 75% (56 out of 75) were categorized into predicted responders (risk score ≤ 3.5) and predicted nonresponders (risk score ≥ 6). At 6 months, the negative predictive value was 81% (21 out of 26) and the positive predictive value was 47% (14 out of 30). CONCLUSION: The pharmacogenetic model predicts nonresponse to MTX monotherapy, but performs better in DMARD naive recent-onset RA patients than in patients with preceding DMARD failure.
BACKGROUND: The performance of a clinical pharmacogenetic model to predict nonresponse of methotrexate (MTX) monotherapy in patients with established rheumatoid arthritis (RA) and failure of disease-modifying antirheumatic drugs (DMARDs) was studied. METHODS: For 75 RApatients receiving MTX monotherapy for 6 months, DNA and clinical data were available. Risk scores for nonresponse at 6 months (disease activity score >2.4), were calculated using the pharmacogenetic prediction model utilizing four clinical factors and four polymorphisms in the genes MTHFD1, AMPD1, ITPA and ATIC. RESULTS: At 6 months, there were 25 responders and 50 nonresponders. Using the clinical pharmacogenetic prediction model, 75% (56 out of 75) were categorized into predicted responders (risk score ≤ 3.5) and predicted nonresponders (risk score ≥ 6). At 6 months, the negative predictive value was 81% (21 out of 26) and the positive predictive value was 47% (14 out of 30). CONCLUSION: The pharmacogenetic model predicts nonresponse to MTX monotherapy, but performs better in DMARD naive recent-onset RApatients than in patients with preceding DMARD failure.
Authors: Barbara Jenko; Matija Tomšič; Biljana Jekić; Vera Milić; Vita Dolžan; Sonja Praprotnik Journal: Front Pharmacol Date: 2018-01-25 Impact factor: 5.810
Authors: Maurits C F J de Rotte; Saskia M F Pluijm; Pascal H P de Jong; Maja Bulatović Ćalasan; Nico M Wulffraat; Angelique E A M Weel; Jan Lindemans; J M W Hazes; Robert de Jonge Journal: PLoS One Date: 2018-12-10 Impact factor: 3.240
Authors: Rosario López-Rodríguez; Aida Ferreiro-Iglesias; Aurea Lima; Miguel Bernardes; Andrzej Pawlik; Agnieszka Paradowska-Gorycka; Jerzy Świerkot; Ryszard Slezak; Vita Dolžan; Isidoro González-Álvaro; Javier Narváez; Rafael Cáliz; Eva Pérez-Pampín; Antonio Mera-Varela; Laura Vidal-Bralo; José Gorgonio Acuña Ochoa; Carmen Conde; Juan J Gómez-Reino; Antonio González Journal: Sci Rep Date: 2018-05-09 Impact factor: 4.379
Authors: Jamie C Sergeant; Kimme L Hyrich; James Anderson; Kamilla Kopec-Harding; Holly F Hope; Deborah P M Symmons; Anne Barton; Suzanne M M Verstappen Journal: Arthritis Res Ther Date: 2018-07-13 Impact factor: 5.156