Tuesday, 16 September 2014

Daclizumab HYP a new kid on the block

Othman AA, Tran JQ, Tang MT, Dutta S.Population Pharmacokinetics of Daclizumab High-Yield Process in Healthy Volunteers: Integrated Analysis of Intravenous and Subcutaneous, Single- and Multiple-Dose Administration. Clin Pharmacokinet. 2014 Sep 12. [Epub ahead of print]

BACKGROUND AND OBJECTIVE:Daclizumab is a humanized monoclonal antibody that blocks the α-subunit of the interleukin-2 receptor with demonstrated benefits in the treatment of multiple sclerosis. The present work aimed to characterize the pharmacokinetics of daclizumab high-yield process (HYP) in healthy volunteers.
METHODS:Three double-blind, randomized, placebo-controlled, phase I studies evaluated the pharmacokinetics of daclizumab HYP in healthy volunteers following single subcutaneous administration (50, 150, or 300 mg), multiple subcutaneous administrations (100 or 200 mg biweekly with a 200 mg loading dose), or single intravenous administration (200 or 400 mg). Measurable serum concentrations (n = 925) from 70 subjects treated with daclizumab HYP in the three studies were analyzed using non-linear mixed-effects modeling.
RESULTS:A two-compartment model with a first-order absorption and elimination adequately described daclizumab HYP pharmacokinetics. Daclizumab HYP clearance, inter-compartmental clearance, and central and peripheral volumes of distribution were 10 mL/h, 44 mL/h, 3.89 L, and 2.52 L, respectively, scaled by [bodyweight (kg)/70] with 0.54 and 0.64 exponents for clearance and volume parameters, respectively. Lag-time, mean absorption time, and absolute bioavailability (100-300 mg) for subcutaneous administration were 2 h, 4.6 days, and 84 %, respectively. Bodyweight explained only ~20 % of daclizumab HYP pharmacokinetic variability. With this limited dataset, sex, age, race, or presence of antibodies did not correlate with daclizumab HYP clearance. The estimated effective half-life was 21-25 days. The developed model was robust in bootstrap evaluation and predicted the data adequately in stochastic simulations.
CONCLUSIONS:Daclizumab HYP is characterized by slow clearance, linear pharmacokinetics (at doses ≥100 mg), high subcutaneous bioavailability, and a half-life suitable for monthly administration.

This is data of early studies looking at how people handle daclizumab (an antibody that blocks T cell function and augments a subset of Natural killer cells. They found they could get the dose for a once a month dosing. The results of the phase III trial inMS was presented at ECTRIMS2014 and there was a significantly better effect than using beta interferon. The major side effect was skin reactions at the site of injections, which could be treated with steroids. So this is going to be the next new MS drug. We will report on this as the data is published

ClinicSpeak: holistic approach to MS version 4.0

My holistic approach to MS: a work in progress. #ClinicSpeak #MSBlog #MSResearch

"As promised I have  tried to update and expand my London Tube map analogy of the holistic approach to MS. The idea is to one day link this map to click through topics to help MSers self-manage their disease. Please feel free to comment on the map and suggest changes or additions. Please note this is a work in progress and it will continue  to evolve over time and I am sure contains errors. This upgrade is the result of being jet-lagged and having time on my hand due to insomnia."

Final Reminder: Imperial College MS Study Day 26th September 2014

Final Reminder: Imperial College MS Study Day 26th September 2014. #MSBlog #MSResearch

"If you live in London you may want to attend the Imperial College MS Study Day on the 26th September 2014. There a few places left. Please register online if you want to attend. I have embedded the programme for your information. "

MS Day: How can Nurses Help?

UCL/Barts research day presentations

MS Nurse Team: Q & A
On behalf of my brother, big thank you to Freya from Royal London and all the MS nurses, providing an extremely amazing support every day and being there throughout everything.

This month MS Trust newsletter mentioned that the average ratio of patients to a nurse should be 500/1. However it is currently approaching - 800/1. In Ealing, which is the biggest borough in London with MS patients, the ratio is up to nearly 1000/1 and it is getting worse. The relationship and ratio between nurses and patients in the NHNN is great, but I do not think it is reflected on the country at all. MS Trust has done an awful lot of work doing research on numbers and looking at the caseloads. I think it is going to be an ongoing challenge. A lot of it will be on developing the services but also on having the support to develop the services. It is a common goal for community or hospital nurses to be able to help you to manage MS as well as possible.

Are the MS nurses have been or will be affected by the governmental cuts?
Yes, we are affected by the government cuts. It is always difficult to balance and also know how much government will give us. The MS trust has recently done a research to see how many patients we should have per nurse and they also have done a bit of work on the impact that we have on you. Hopefully we will be able to use this evidence to show the government how essential MS nurses are to these services. The new NICE guideline that comes out in October and the draft guideline definitely mentions how important MS nurse are for the team. We have to hope it will be a positive move forward. We always rely on 2 charities and they are our most avid supporters, and they fight really hard to make sure that there are always MS nurses around.