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Simba15
01-29-2013, 06:52 PM
I have read there are about 114 of "me" in the world - R334W. Anyone here with that?

jricci
01-30-2013, 10:41 PM
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
01-30-2013, 11:04 PM
jricci...if you are pancreatic suffcient are you on kalydeco.? if not id ask to get on asamph

JENNYC
01-31-2013, 10:08 AM
I agree with Aboveallislove! Pancreatic sufficient sounds like a winner!! Abby is not pancreatic sufficient and it still helped her...not the way that it helped the G551D's but enough so that I can't imagine going back!! :)

Imogene
01-31-2013, 10:32 AM
There are 5 members on our site with this mutation.

jricci
01-31-2013, 01:37 PM
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/[email protected]/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.

Aboveallislove
01-31-2013, 01:53 PM
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.

JENNYC
02-01-2013, 09:45 AM
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. :)

jricci
02-01-2013, 12:25 PM
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 : )

JENNYC
02-01-2013, 04:27 PM
We have Humana and all that was required was a prior authorization which was a very small questionaire that the dr filled out and faxed in and BOOM we have approved Kalydeco for 2 years!! I feel very blessed. I hope you start feeling better no matter what!!!

Simba15
02-01-2013, 09:02 PM
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?

Simba15
02-01-2013, 09:03 PM
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/[email protected]/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.

I don't understand this. Can you explain in baby talk?

Simba15
02-01-2013, 09:03 PM
There are 5 members on our site with this mutation. Great. would like to talk to them and compare symptoms and stories.

amalone
04-11-2014, 03:46 PM
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.

jricci
04-12-2014, 05:23 PM
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 canít come soon enough for me as Iíve had a difficult year and saw my PFTs fall to 29%, the lowest theyíve ever been. Thankfully, my PFTs are recovering now. I am counting on this drug to be life changing for me. I know it canít reverse damage already done, but if it stops progression then this would be huge for me. Iíll be sure to post an update if I hear anything.

jricci
11-11-2014, 09:48 PM
Well I have an update! Itís 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 Iím 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 30ís/low 40ís). 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 4th dose. I took a deep breath in the cool outside air and could feel the air reaching parts of my lungs that I havenít felt in a very long time. Another big change Iíve 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 couldnít 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, Iíll share my story via this forum in the hopes that it will help others with residual function mutations. Hereís to new beginningsÖ

foxalive
11-25-2014, 04:24 AM
Hello everyone :)Thank you for having created this topic!I was so glad to find it! This is an incredibly great to meet you here :)Iím 32 y.o. I have r334w-f508del. And B.Cepacia many years in my lungs.I am from Russia, sorry for my English, itís so poor.

jricci
11-25-2014, 10:38 AM
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.

nocode
11-27-2014, 02:48 AM
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.

foxalive
11-27-2014, 03:53 AM
Hi, nocode!
I hope in your country Kalydeco is available and you can give it a try!
Could you clarify what you have second mutation? You wrote - it does not seem to exist :)
What an infection in your lungs?

nocode
11-27-2014, 10:45 AM
Hi Foxalive! My other mutation is N1303K (I checked).
What do you mean by your last sentence? :)

Greetings to Russia.

foxalive
11-27-2014, 05:08 PM
Nocode, I have b.cepacia in my lungs.
What kind of bacteria in your lungs?

nocode
11-27-2014, 06:58 PM
Pseudomonas. Can you get rid of cepacia? Have you noticed a decline since you got it?

foxalive
11-27-2014, 07:22 PM
I have Cepacia for about six years.
At first condition deteriorated badly, gradually has stabilised. But she never got so still. Now it is relatively stable.
I tried to get rid it, but it did not work out. In Russia, the bad quality of care.

Simba15
01-24-2015, 10:48 AM
I had sinus surgery and it helped immensely. No kalydeko here
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.

Simba15
01-24-2015, 10:52 AM
Only 164 people in the world???!!!:eek: So doctors know NOTHING about us!

Maria Torres
03-18-2015, 09:59 AM
My daughter is one of the 164. She is 18 months old right now. She is F508Del and R334W and pancreatic insufficient. She has luckily not had any hospitalizations yet and we have been through RSV and 2 cases of bronchitis. I am happy to see all the older people in the group it helps to know she has a very good chance at a long life. I hope that they keep testing the mutations with Kalydeco. I have heard that some people have seen positive changes and some not.

JDsmom
06-12-2015, 03:50 AM
Well I have an update! Itís 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 Iím 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 30ís/low 40ís). 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 4th dose. I took a deep breath in the cool outside air and could feel the air reaching parts of my lungs that I havenít felt in a very long time. Another big change Iíve 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 couldnít 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, Iíll share my story via this forum in the hopes that it will help others with residual function mutations. Hereís to new beginningsÖ

Hi - may I ask are you still on Kalydeco and still keeping the good results? We are in the same boat with R347P - Class 4/Conductance, not responsive in vitro but also PS and very keen to try Kalydecco or - as DF508 as well - the combination drug.

jricci
06-25-2015, 09:13 PM
Hi - may I ask are you still on Kalydeco and still keeping the good results? We are in the same boat with R347P - Class 4/Conductance, not responsive in vitro but also PS and very keen to try Kalydecco or - as DF508 as well - the combination drug.

Sorry I havenít responded sooner. Just seeing this now. Yes, I continue to do well on Kalydeco. Progress did plateau quickly for me. But in my eyes, stability is progress considering I felt like my health has been faltering for the last 3+ years. The most noticeable differences are decreased shortness of breath, decreased cough, and the ability to sleep through most nights without waking up coughing. I was getting up at least once a night with pretty intense coughing attacks for the last couple of years. Also exercise isnít as grueling as it was. I feel like air is moving more freely and I can take more air in with each breath. I think because my lung function was pretty low (31%) when I started Kalydeco, the results I felt initially were quick and dramatic. Going from 31% to 42% lung function in 5 days felt miraculous. Truly Ėthere is no other word to describe it. I was at a point where even IV antibiotics werenít giving me much relief. And if they did, it was temporary.
I still have bad days, but prior to Kalydeco my good days were getting few and far between. And even my ďbadĒ days are so much more tolerable now that I have the knowledge that my progression has slowed and my health has stabilized. The fear of my future is no longer the first thing I think about when I wake up.

Since your son is pancreatic sufficient, I think there is a very good possibility that Kalydeco will be effective to some capacity. I do want to mention that my sweat chloride only decreased by 10%. This may explain the poor in vitro results. But I think what this proves is that it takes very little correction of CFTR function to notice a clinical difference. Is your doctor willing to write a prescription? Do you need any help with getting journal articles? Iíd also be willing to share my medical records with your doctor if he needs some convincing to write a prescription. Let me know if there is anything I can do to help.

Simba15
06-26-2015, 09:37 AM
Why are people recommending Kalydeco if we are not sick?
Kalydec

Kalydec

Simba15
06-26-2015, 09:39 AM
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 guess I am very lucky and I pray I stay that way. My FEV is 111-114. I have colitis which I am managing with diet and L-Glutamine. Never took Kalydeco b/c I am not sick. Why are people taking it?

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