Can sweat chloride numbers drop on their own?

[JENNYC]

Hey guys I am just wondering if sweat chloride numbers can drop by 12 points or more on their own? We are going to see Abby's dr Friday and I want to be prepared for whatever he might say. Our last 2 conversations he was very negative and explained away everything. I hope that he surprises me and is happy as we are with her drop in sweat chloride!! For me it just confirms what I was already seeing. I have tried to google it and I haven't found anything. Anything you have would be much appreciated

 

[Aboveallislove]

Hey,
Don't know the answer to that, but from everything I've seen for those being tested on Kalydeco, if anything the #s have gone up as they get older. I think there were several that have their kids #s from diagnosis, pre-K, post K, etc. and the pre-K was higher than the diagnosis for everyone I remember seeing. And make sure you hit the doctor with "at a minimum it was a 21 point improvement and a 19% improvement. That the Kalydeco study had about a 40 point improvement, but the combo which is going to Phase 3 had a 10 point improvent and still showed 10% in FEV. AND that SC seems to continue to decrease. Please keep us posted on how it goes!

 

[JENNYC]

Thank you so much!! I will for sure let you know how it goes!! I thought that it usually got higher as they get older. I just want to be prepared. I'm not very good when under pressure It's best if I am prepared going into what might be a stressful situation. I hope that he is as excited as we are!! I don't know why I let myself get all worked up about it!

 

[Aboveallislove]

Jenny--totally understandable. I was getting nervous thinking "I wonder what Abby's doctor will say NOW" so I can imagine how you must be. Hugs

 

[GenH]

Hey guys I am just wondering if sweat chloride numbers can drop by 12 points or more on their own? We are going to see Abby's dr Friday and I want to be prepared for whatever he might say. Our last 2 conversations he was very negative and explained away everything. I hope that he surprises me and is happy as we are with her drop in sweat chloride!! For me it just confirms what I was already seeing. I have tried to google it and I haven't found anything. Anything you have would be much appreciated

Hi Jenny, in a few of the vertex trials there have been drops of about 10 points, which has been statistically significant (this means there is greater than a 95% chance the improvement is due to the medication as opposed to random chance- the calculations also take sample size and placebo change into account). So the change you have seen is similar to the F508del trial results.

To aboveallislove- my sweat chloride was 110 when I was 3 at diagnosis and 102 last week (starting Kalydeco tomorrow). So not necessarily an increase with age. In the G551D 6-11yo trial the baseline was 104 and in the 12+ trial the baseline was 100.2.

 

[JENNYC]

Thanks GenH!! I appreciate it!! Makes me feel better!! I will let yall know how her dr reacts.

 

[Aboveallislove]

Thanks GenH for info on increase in SC.

And Jenny, I love GenH's point re the stat. significant changes. This is from press release:
"One of the two primary endpoints in this study was change in sweat chloride from Day 28 to 56 compared to placebo. There was no decrease in sweat chloride among those receiving placebo from Day 0 to 28 or from Day 28 to 56. In homozygous patients treated with 600mg of VX-809 alone for 28 days, there was a statistically significant mean decrease in sweat chloride of 6.4 mmol/L compared to placebo (p=0.01). An additional mean decrease in sweat chloride of 3.7 mmol/L compared to placebo was observed with combination treatment between Day 28 and 56, which was not statistically significant."

So a change of 6.4 compared to placebo when on JUST 809 was considered stat. significant to a tight probability of .01 (I think that mean only 1% chance it was "coincidence." The 3.7 change was not stat. significant. So I think the strong argument can be made that anything above 7 points is not a coincidence/chance. And you have an established 21 point change--and at minimum 12 but could be easily more. Now the "counter" will be that 809 isn't suppose to "fix" anything in this study and that is 809 and not Kalydeco, BUT the point still seems to remain that SC would not randomly/conicidently drop by 6.4 points--if it could/would then placebos would have that occur too. (Note: It might not have been a 6.4 point drop, but it could have been placebos went up by 2 points and those in the study went down by 4.4 so compared to placebo there was a comparative drop of 6.4. This is likely a combination of a drop and an increase in placebo since study said no one in placebo had a drop in SC.) So GenH's point makes your argument even strong because we have a study showing that SC just doesn't coincidently drop that much!