PhD defence H.R. (Helen) Gosselt

Methotrexate (MTX) is first-line therapy in Rheumatoid Arthritis (RA). Despite its relatively high response rates and safety, up to 40% of RA patients do not benefit from MTX and require step-up treatment with biologic or targeted synthetic disease modifying antirheumatic drugs (b/ts DMARDs). Up to now, treatment response can be determined the soonest at 3 to 6 months from treatment initiation. Since early control of the disease activity results in better long-term outcomes, insufficient responders would benefit from sufficient treatment from the start. To identify insufficient responders prior to MTX treatment initiation there is a need for determinants of insufficient response.This would allow the use of personalized medicine in which MTX is only prescribed in case patients have a high chance of successful response and if not they could step-up treatment directly from the start. In the first part of this thesis we assessed epigenetic and metabolic determinants for insufficient response to MTX. In the second part, we validated a previously developed prediction model for insufficient response to MTX in RA and we assessed the use of machine-learning algorithms compared to conventional multivariable logistic regression in such clinical prediction models.

The public defence will take place at the Prof. Andries Queridoroom, 3rd floor Education Center, Erasmus MC. The ceremony will begin exactly at 13.00 PM. In light of the solemn nature of the ceremony, we recommend that you do not take children under the age of 6 to the first part of the ceremony.