Patient centered decision making: use of conjoint analysis to determine risk-benefit trade-offs for preference sensitive treatment choices.

UNLABELLED: Understanding patient preferences facilitates shared decision-making and focuses on patient-centered outcomes. Little is known about relapsing-remitting multiple sclerosis (RRMS) patient preferences for disease modifying therapies (DMTs). We use choice based conjoint (CBC) analysis to calculate patient preferences for risk/benefit trade-offs for hypothetical DMTs. METHODS: Patients with RRMS were surveyed between 2012 and 2013. Our CBC survey mimicked the decision-making process and trade-offs of patients choosing DMTs, based on all possible DMT attributes. Mixed-effects logistic regression analyzed preferences. We estimated maximum acceptable risk trade-offs for various DMT benefits. RESULTS: Severe side-effect risks had the biggest impact on patient preference with a 1% risk, decreasing patient preference five-fold compared to no risk. (OR=0.22, p<0.001). Symptom improvement was the most preferred benefit (OR=3.68, p<0.001), followed by prevention of progression of 10 years (OR=2.4, p<0.001). Daily oral administration had the third highest DMT preference rating (OR=2.08, p<0.001). Patients were willing to accept 0.08% severe risk for a year delayed relapse, and 0.22% for 4 vs 2 year prevented progression. CONCLUSION: We provided patient preferences and risk-benefit trade-offs for attributes of all available DMTs. Evaluation of patient preferences is a key step in shared decision making and may significantly impact early drug initiation and compliance.

B cell exchange across the blood-brain barrier in multiple sclerosis.

In multiple sclerosis (MS) pathogenic B cells likely act on both sides of the blood-brain barrier (BBB). However, it is unclear whether antigen-experienced B cells are shared between the CNS and the peripheral blood (PB) compartments. We applied deep repertoire sequencing of IgG heavy chain variable region genes (IgG-VH) in paired cerebrospinal fluid and PB samples from patients with MS and other neurological diseases to identify related B cells that are common to both compartments. For the first time to our knowledge, we found that a restricted pool of clonally related B cells participated in robust bidirectional exchange across the BBB. Some clusters of related IgG-VH appeared to have undergone active diversification primarily in the CNS, while others have undergone active diversification in the periphery or in both compartments in parallel. B cells are strong candidates for autoimmune effector cells in MS, and these findings suggest that CNS-directed autoimmunity may be triggered and supported on both sides of the BBB. These data also provide a powerful approach to identify and monitor B cells in the PB that correspond to clonally amplified populations in the CNS in MS and other inflammatory states.