R334w
- Thread starter Simba15
- Start date
I am one of the 114. I also have the combination DF508 and R334W. I'm 41, was diagnosed at age 7 with a sweat chloride of 110, FEV1 is 48%, colonized with MRSA and pseudomonas, pancreatic sufficient, history of severe pancreatitis. For the past year and a half, I've been struggling a lot with wheezing and inflammation. I'm currently in pulmonary rehab with does seem to be helping with the inflammation.
Aboveallislove
Super Moderator
jricci...if you are pancreatic suffcient are you on kalydeco.? if not id ask to get on asamph
I was very hopeful as I did research and discovered that my mutation in a class IV conductance mutation and since I have CFTR and the cell surface that Kalydeco should be effective. However, as I did further research, I was disappointed as the in-vitro studies of my mutation,r334w,did not show promising results with Kalydeco. VanGoor classifies r334w as a severe conductance mutation. See the following slides: http://www.flickr.com/photos/66477137@N05/7670225762/.
Even with these results, I still believe Kalydeco should have some effect on me since I am pancreatic sufficient and must have some functional CFTR at the cell surface for this to be possible. I was very close to participating in the Ivacaftor clinical trial in Denver, however I am not able to since you are required to stop hypertonic saline for the duration of the study. Ironically, my doctor had stopped HTS on me about 3 months ago, thinking that I may have developed a sensitivity to it and it may be contributing to my inflammation. This 2 week trial without HTS did not go well and my PFTs dropped about 15%. So I know I wouldn't be able to omit it from my regime for the duration of the clinical trial which I believe is 7 months. I have not attempted to see if my insurance company would approve Kalydeco off-label, but highly doubt they would with the research that has shown it to be ineffective with my mutation during in-vitro studies.
Even with these results, I still believe Kalydeco should have some effect on me since I am pancreatic sufficient and must have some functional CFTR at the cell surface for this to be possible. I was very close to participating in the Ivacaftor clinical trial in Denver, however I am not able to since you are required to stop hypertonic saline for the duration of the study. Ironically, my doctor had stopped HTS on me about 3 months ago, thinking that I may have developed a sensitivity to it and it may be contributing to my inflammation. This 2 week trial without HTS did not go well and my PFTs dropped about 15%. So I know I wouldn't be able to omit it from my regime for the duration of the clinical trial which I believe is 7 months. I have not attempted to see if my insurance company would approve Kalydeco off-label, but highly doubt they would with the research that has shown it to be ineffective with my mutation during in-vitro studies.
Aboveallislove
Super Moderator
Wow. You're on top of it. And thanks for much for info on hts. A friend asked if our DS would be in a trial of the combo and I said he's too young but I don't think we would anyway because he's on hts and it works really well for him and I wouldn't want to stop. I think I'd ask the doctor to prescribe and see what happens. If they ask for letter of medical necessity the pancreatic sufficiency and residual function might do it, and he could suggest a 3 month study with SC before and after.
I again agree!!! I can't tell you what a difference it made in Abby who does not have the right mutations...I can not imagine going back to the way things were!! All they can do is tell you no. I wrote a detailed summary of how she did on it in CFTR Modulation and Gene Therapy Talk this morning....check it out 
When Abby started Hyper-Sal I could see a huge difference!! This is 10x more of a difference and yes she is still on Hyper-sal.
When Abby started Hyper-Sal I could see a huge difference!! This is 10x more of a difference and yes she is still on Hyper-sal. That's very encouraging news Jenny. I'm so happy for her. It's a shame your doctor isn't on board. I know how important it is to have a good relationship with your doctor. What insurance do you have? Did it have to go through an appeal process? I will talk to my doctor and get his thoughts on it. You're right, it never hurts to try!
Aboveallislove- Hypersal wasn't allowed in the study I was speaking of because change in baseline sweat chloride level was one of the outcome measures. It is thought that hypersal can influence sweat chloride values. I'm not sure with the future combination drug studies if sweat chloride will be an outcome measure. I thought I remembered reading somewhere that change in FEV1 will be the main measure. So Hypersal may be allowed in future studies. I'm not certain.
Thank you both for the encouraging words. Hope is always uplifting : )
Aboveallislove- Hypersal wasn't allowed in the study I was speaking of because change in baseline sweat chloride level was one of the outcome measures. It is thought that hypersal can influence sweat chloride values. I'm not sure with the future combination drug studies if sweat chloride will be an outcome measure. I thought I remembered reading somewhere that change in FEV1 will be the main measure. So Hypersal may be allowed in future studies. I'm not certain.
Thank you both for the encouraging words. Hope is always uplifting : )
Simba15
Member
Ok what are r334W people's level of functioning and symptoms?
I started taking biaxin one year ago. I take it daily. it helped with my sinus infections, bronchitis. in the last year my GI symptoms are worse. getting that checked on monday. I work, take long walks daily (about 3 miles a day). I also have sleepapnea which I think was caused by the CF.MY ENT said my sinus cavity never developed.
No one would know I have CF really. I am thankful for that. I work alot, so i am tired. If i get stressed it does immediately go to my chest. My GI symptoms might be pancreas but idk yet. Since R334W is supposed t be the "mild" CF gene, are other here doing about the same as me?
I started taking biaxin one year ago. I take it daily. it helped with my sinus infections, bronchitis. in the last year my GI symptoms are worse. getting that checked on monday. I work, take long walks daily (about 3 miles a day). I also have sleepapnea which I think was caused by the CF.MY ENT said my sinus cavity never developed.
No one would know I have CF really. I am thankful for that. I work alot, so i am tired. If i get stressed it does immediately go to my chest. My GI symptoms might be pancreas but idk yet. Since R334W is supposed t be the "mild" CF gene, are other here doing about the same as me?
Simba15
Member
I don't understand this. Can you explain in baby talk?
Simba15
Member
Great. would like to talk to them and compare symptoms and stories.
A
amalone
Guest
I wonder if you all would be willing to resurrect this conversation with an update. I am one of the few people with DF508 and R334W. I would love to hear if anyone with that mutation has gotten a chance to try Kalydeco since you all last posted.
I am fairly mild in my Cf presentation. My FEV1 hovers around 75% of predicted. I am pancreatic sufficient and have manageable sinus issues. A couple docs have danced around sinus surgery but decided against it. Presently my primary method of controlling my pulmonary function is Hypertonic Saline and regular running.
I am fairly mild in my Cf presentation. My FEV1 hovers around 75% of predicted. I am pancreatic sufficient and have manageable sinus issues. A couple docs have danced around sinus surgery but decided against it. Presently my primary method of controlling my pulmonary function is Hypertonic Saline and regular running.
Unfortunately I still haven't had the chance to try Kalydeco. I was enrolled in the combination VX-809/Kalydeco trial and went through the screening process, but then had an exacerbation during the screening period so I was no longer eligible to be on the study. By the time I could have re-screened, the study was closed. I was disappointed to say the least. I haven't heard of anyone else with our mutation that has tried Kalydeco, but I really believe that this drug should work for those of us with this mutation that are pancreatic sufficient. I'm hoping the results from the pilot study testing Kalydeco and residual CFTR function are released soon. If the results from this study are positive and vertex submits a drug application to FDA for approval of Kalydeco for those who have evidence of residual CFTR function then we would be included. I believe the study closed in the fall, so I would imagine the results should be released soon. It can’t come soon enough for me as I’ve had a difficult year and saw my PFTs fall to 29%, the lowest they’ve ever been. Thankfully, my PFTs are recovering now. I am counting on this drug to be life changing for me. I know it can’t reverse damage already done, but if it stops progression then this would be huge for me. I’ll be sure to post an update if I hear anything.
Well I have an update! It’s a long one. My doctor attended the NACFC and spoke to other doctors about their experiences with off label Kalydeco use for residual function mutations. After hearing many success stories, he decided to prescribe it for me. He was cautiously optimistic that it would help me since I’m pancreatic sufficient (have residual function). My mutations are DDF508 and r334w. (r334w is a class IV conductance mutation. It is one of the few conductance mutations that did not show a significant response to Kalydeco in in-vivo studies.) We were expecting pushback from my insurance company and we were armed with a lot of information to appeal if it was denied. But my insurance company covered it immediately, no questions asked. I started Kalydeco 5 days ago. My lung function was at 31% (this was after an unsuccessful round of IV antibiotics. I would say I consider my baseline lung function to be in the upper 30’s/low 40’s). I began noticing a difference within a matter of days! The biggest change I noticed was decreased inflammation. I have had a lot of issues with wheezing in the last 3 years. I could feel my lungs opening up by the 4[SUP]th[/SUP] dose. I took a deep breath in the cool outside air and could feel the air reaching parts of my lungs that I haven’t felt in a very long time. Another big change I’ve noticed is that my mucus is thinner, similar to what it is after a hypertonic saline treatment, except it was this consistency the whole day! I did a repeat PFT today and my lung function was up to 41%. 31% to 41% in 5 days! My doctor said he couldn’t remember the last time my lungs sounded so good. Unbelievable! I asked my doctor if Vertex was keeping a database of mutations that have responded/not responded to the off-label use of Kalydeco. He said that the CFF collects data for the registry and this information would be included but it is only released annually. I plan on calling Vertex and asking them if there is any way for them to keep track of off label use. It only makes sense that this information should be officially collected and shared with patients and doctors alike. But in the meantime, I’ll share my story via this forum in the hopes that it will help others with residual function mutations. Here’s to new beginnings…
Glad you found this forum foxalive. According to the CF registry, there are 164 people in the world with our mutation. I would have never thought I would be able to be touch with someone that shares my mutation, let alone someone from Russia! Technology is amazing. I sent you a PM.
Hi everyone. I'm a 31 year old European female who also has this mutation! My second one is N3103w (wow can't remember for sure now if the numbers are right).
My lung function has been in the low 30s for a really long time, around 10 years or so.
Other than a crappy lung function I feel pretty good otherwise. I am pancreatic sufficient too. I have only had 2 hospitalizations for lung infections in my life, which is low from what I read on the forums.
I am 5'3" and 110 pounds. I have no weight issues.
Because of my low lung function I was evaluated for transplant a year ago but did not go on the list because of all the things I am still able to do unassisted (with no supplemental O2), and because of a stable lung function.
I do use O2 when I sleep and during exercise (2L). I have recently started to use 1-2L for most of the day when I'm home and I feel better! It gives more energy for other things.
I would love to try Kalydeco; I didn't know it could have such a great effect on this mutation. Not sure how it works in the Netherlands though.
My lung function has been in the low 30s for a really long time, around 10 years or so.
Other than a crappy lung function I feel pretty good otherwise. I am pancreatic sufficient too. I have only had 2 hospitalizations for lung infections in my life, which is low from what I read on the forums.
I am 5'3" and 110 pounds. I have no weight issues.
Because of my low lung function I was evaluated for transplant a year ago but did not go on the list because of all the things I am still able to do unassisted (with no supplemental O2), and because of a stable lung function.
I do use O2 when I sleep and during exercise (2L). I have recently started to use 1-2L for most of the day when I'm home and I feel better! It gives more energy for other things.
I would love to try Kalydeco; I didn't know it could have such a great effect on this mutation. Not sure how it works in the Netherlands though.