Thursday, 24 July 2014

What do US MSers think about switching drugs

Salter AR, Marrie RA, Agashivala N, Belletti DA, Kim E, Cutter GR, Cofield SS, Tyry T.Patient perspectives on switching disease-modifying therapies in the NARCOMS registry.
Patient Prefer Adherence. 2014 Jul 4;8:971-9. doi: 10.2147/PPA.S49903. eCollection 2014

.INTRODUCTION: The evolving landscape of disease-modifying therapies (DMTs) for multiple sclerosis raises important questions about why patients change DMTs. Physicians and patients could benefit from a better understanding of the reasons for switching therapy.
PURPOSE: To investigate the reasons patients switch DMTs and identify characteristics associated with the decision to switch.
METHOD: The North American Research Committee on Multiple Sclerosis (NARCOMS) Registry conducted a supplemental survey among registry participants responding to the 2011 update survey. The supplemental survey investigated reasons for switching DMT, origin of the discussion of DMT change, and which factors influenced the decision. 
RESULTS: Of the 691 eligible candidates, 308 responded and met the inclusion criteria (relapsing disease course, switched DMT after September 2010). The responders were 83.4% female, on average 52 years old. The most recent prior therapy included first-line injectables (74.5%), infusions (18.1%), an oral DMT (3.4%), and other DMTs (4.0%). The discussion to switch DMT was initiated almost equally by physicians and participants. The primary reason for choosing the new DMT was based most frequently on physician's recommendation (24.5%) and patient perception of efficacy (13.7%).
CONCLUSION: Participants frequently initiated the discussion regarding changing DMT, although physician recommendations regarding the specific therapy were still weighed highly. Long-term follow-up of these participants will provide valuable information on their disease trajectory, satisfaction with, and effectiveness of their new medication.

Whilst the results are what they are and it is not surprising that there were large switches from the injectables because we know they have a a lower efficacy levels,  but why are the switches occurring?  

If you are treating to target of No evidence of Disease activity, it makes sense to switch and escalate. Prof G has mademany posts on this aspect 

What causes damage in MS

Azevedo CJ, Kornak J, Chu P, Sampat M, Okuda DT, Cree BA, Nelson SJ, Hauser SL, Pelletier D. In vivo evidence of glutamate toxicity in multiple sclerosis.Ann Neurol. 2014 Jul 9. doi: 10.1002/ana.24202. [Epub ahead of print]

OBJECTIVE: There is increasing evidence that altered glutamate (Glu) homeostasis is involved in the pathophysiology of multiple sclerosis (MS). The aim of this study was to evaluate the in vivo effects of excess brain Glu on neuroaxonal integrity measured by N-acetylaspartate (NAA), brain volume, and clinical outcomes in a large, prospectively followed cohort of MS subjects.
METHODS: We used multivoxel spectroscopy at 3T to longitudinally estimate Glu and NAA concentrations from large areas of normal-appearing white and gray matter (NAWM and GM) in MS patients (n = 343) with a mean follow-up time of 5 years. Using linear mixed-effects models, Glu was examined as a predictor of NAA decline, annualized percentage brain volume change, and evolution of clinical outcomes (Multiple SclerosisFunctional Composite [MSFC], Paced Auditory Serial Addition Test-3 [PASAT], and Expanded Disability Status Scale). Glu/NAA ratio was tested as a predictor of brain volume loss and clinical outcomes.
RESULTS: Baseline Glu[NAWM] was predictive of accelerated longitudinal decline in NAA[GM] (-0.06mM change in NAA[GM] /yr for each unit increase in Glu; p = 0.004). The sustained elevation of Glu[NAWM] was predictive of a loss of 0.28mM/yr in NAA[NAWM] (p < 0.001) and 0.15mM/yr in NAA[GM] (p = 0.056). Each 10% increase in Glu/NAA[NAWM] was associated with a loss of 0.33% brain volume/yr (p = 0.001), 0.009 standard deviations/yr in MSFC z-score (p < 0.001), and 0.17 points/yr on the PASAT (p < 0.001).
INTERPRETATION: These results indicate that higher Glu concentrations increase the rate of NAA decline, and higher Glu/NAA[NAWM] ratio increases the rate of decline of brain volume, MSFC, and PASAT. This provides evidence of a relationship between brain Glu and markers of disease progression in MS

Glutamate is the major excitatory neurotransmitter that control nerve function. However if too much is produced it can cause excitotoxicity. NAA is the second-most-concentrated molecule in the brain after the amino acid glutamate. It is detected in the adult brain in neurons, and is a marker of nerve content. The more glutamate that is present is associated with nerve loss and associates with brain shrinkage. This process occurs in stroke, but there are few good treatments for human stroke but loads of treatments for experimental stroke. In humans such treatments for stroe invariably fail because they are not given early enough after the stroke. In MS however you could give the stroke drug even before the excitotoxicity has occurred and so the chances of success are greater.