Treatment for the mildly diseased

[ethan508]

I've got my clinic visit coming up next week and am conflicted about starting Orkambi. I don't love the price (even though I won't bear the brunt of the price, I don't love making my self-insured employer pay), I'm nervous about possible side effects especially those involving the liver, and am little disappointed that it doesn't seem to be as effective as Kalydeco. My lung disease has been somewhat mild. I only do Tobi 2-3 months of the year usually during flare up in the winter, I've yet to be hospitalized for a pulmonary exacerbation, I cough and produce but it is rare for it to be any sort of disruptive. I'm still at the point that anyone that finds out I have CF is surprised (and I'm able to keep that group fairly small), outside of the time commitment for treatments I'm able participate in any activity I want, I even completed a 10k race last weekend at an 8:30 min/mile pace. I still have downs, I'm tired (was once told I nap at a level twice my age), I get depressed and stressed, I tend to catch many of the bugs going around and when caught they hit me fairly hard. But still, I'm just not sure if I'm ill enough to require/deserve/risk $250k in brand new treatment.

Irrationally, a part of me is afraid. If I don't take Orkambi, then I have a few more weapons on the shelf when things start to go south. I'll protect myself from being disappointed in a sub-optimal treatment. In general, I've never been super cutting edge or overly aggressive in treating my disease, but I am super compliant once I start a treatment (I've maybe missed 1 or 2 Vest/Neb sessions in the last year). So any thoughts? Any things I should discuss with my Clinic team (I've heard rumors my clinic isn't focusing on getting Orkambi to those with PFT over 70%)? Any tools you use when you are decided to start a new treatment? Any opinions on being aggressive with mild disease?

PS> On a re-read this post does feel like complaining about 'first world problems' and I'm glad I have the luxury of decent health. But that being said, the above concerns are still valid to me.

 

[welshwitch]

Super valid points, Ethan! Just because a drug is a available, doesn't make it something you NEED to take. Especially if you don't feel you especially need it. I'm also interested in the insurance issue. Do you work for a small company? Is your employer going to know that you specifically are bumping up their premiums? If this is the issue, I'd call Beth Sufian (attorney with CF who does pro bono work for CF-ers). I called her once with a similar fear and she had some great advice. Isn't that what health insurance is for -- covering meds?

Insurance issues aside, I'd probably still try Orkambi if I qualified.

 

[leecee]

I don't have CF but my daughter does and I had the same concerns when they started her on Kalydeco. The issues with liver function concern me. She does not feel different or better and I was told she would not feel a change. Is it better for her to take it in the long run? I have no idea. I absolutely hope so. Her doctor thought she should be on it because of her bronchiectasis. I wish I had advice for you but unfortunately I can't see into the future so I'm of no help.

 

[Aboveallislove]

Hey Ethan,
I have a ton of "jumbled" thoughts, but I’ll try to organize somewhat. Obviously, this is coming from someone very "rah rah" on Kalydeco and Orcambi and I have always taken the position that some improvement, even slight, is worth it with a drug with a safe profile. I know we have respectfully disagree at times (at least I hope I’ve been respectful...you always have). But I must admit that now that Orcambi is a reality and as a mom needing to give consent, I look more seriously at the side effects and also especially with those of late posting of some issues. So, with that backdrop, here’s where I’m at:

We know what CF does. We know that sometimes we don’t see the damage, but it is there. Our son has been VERY blessed to have never had an exacerbation or sinus issues and so far has only culture staph and h-influenza (later of which has been gone for 2 years). So I think: Why "risk" it now, since he is doing so well. But his Xrays are showing more inflamation. Minor still, but it is still there. And if he doesn’t use Orcambi and then gets an exacerbation and all of the complications that could bring, or cultures a bad bug, I have a hard time living with that decision. Yes, the drug could cause problems, but the FDA has approved it and even the 1 no vote saw no real safety concern. The real concerns will be monitored for liver (those with issues returned to stable when they went off the drug) and cataracts. And with me, I never blame myself for decisions made when I didn’t know something,...I make the best decision knowing what I know then...Now for you it is different because you aren’t making the decision for a child but for yourself. But as far as your concerns for the sideeffects, the liver can be tested and the objective science has shown it to be safe.

But what about the benefit: The drug has some "high" responders. You might be one of those and frankly I’d think you have a better shot than most because of your great stable status...you must have come modifying genes that are helping the CFTR function somehow. The only way you will know is if you try it. If it were me, I’d give it 6 months. You can always stop and who knows that stop might make you realize it is doing wonders. Also, it might be just a minor improvement, like you are less tired, but that does impact others too. DH has a medical condition (not CF) that leaves him very tired and fatigued and it is hard on him but also on me and DS. That extra energy is not just for you both your family. And staying the decline until better drugs are available might also mean extra years later with your grandchildren! You can monitor the liver and maybe even look at other assessments such as your FEV, xrays, cultures (maybe you’ll get rid of a bug), or sweat test to see how you are responding. So I guess that’s my bottom line of what I would do in your case.

Finally, re the cost: Your concern about your employer and being a good steward of their resources is admirable. I guess you could always try to do a 661 study instead or see if you could carry your own insurance so it doesn’t hit your employer but an insurance company which might be better able to spread the cost more broadly. For us, my insurance allows for mail order or pharmacy and the mail order saves like $30K a year, whichh the the state’s supplemental insurance covers as co-pay coverage, but the states prefers you to use the pharmacy ...even when I explained it. (That’s without Orcambi). And it is jumping threw hoops and hours of extra time to get reimbursed but I couldn’t in conscience have the state pay the co-pay at that cost to the state which might mean that the program becomes so fiscally unsound that it isn’t there for other Cfers. Yes, someone is still paying, but the cost is spread more with the large employer’s insurance. So maybe you can find another option working with the employer to keep you separate from the rest.
Anyway, those are my thoughts. Good luck with the decision.

 

[franzie2984]

I understand your feelings and thoughts completely. I feel exactly the same way. I am wary of taking Orkambi because the results don't look terribly promising and I am already fairly healthy for someone in their 30s with homozygous 508 mutations -as you have said you are as well. My doctor did prescribe Orkambi for me and I am waiting to see if my insurance will approve it. My lung function is over 70% (it's about 80% these days) so I am not sure why your clinic would not also prescribe it for you with your lung function level.

I too, am worried about the possible side effects. On that note- I have personally been a late joiner (not proud of it-just the truth) to doing many treatments, partly because my parents were pretty wary of my taking pulmozyme and the like, and when I was born most of the treatments were not available yet -my lung function was also well over 100% throughout my childhood. I just started doing the vest and inhaled medications at about age 27..... Now that I am doing slightly worse than when I was younger-I can see the benefit of trying the new treatments and will try the Orkambi when I get approval. I don't regret not being as compliant or trying new treatments when I was younger, but had I known then what I know now, I probably would have done them.

That being said, thanks allaboveislove! Your post have given me a different perspective on Orkambi--

 

[Katie Low]

franzie2984

I am also a late joiner. I am now 27 and my lungs were over 100% just until a couple of years ago. Im now at 95% and doing pulmoyzine and hypertonic saline once daily. When did your numbers start going down?

 

[windex125]

I went to clinic last Thurs. after xray,blood work,vitals the genetic person came in and discussed this new drug with me. My mutations are of course D508 and a V #cannot remember the numbers but she did tell me that out of 88,000 people there are only me and one other person with these 2 mutations. Never knew that. My pfts are 49-50% they have been this number for years. I have only one functioning lung the other is collapsed for years (I am thinking who ever is reading right now is saying if she talks about that collapsed lung one more time lol) due to the collapse I have mediastinal shift everything from the larynx down has been pushed to the right, very bad Acid Reflux, severe bronchiectasis, and I culture MAC for years now, Gastroparsis, PI (just became that in 2014), loss of hearing due to inhalation of Tobi before it was legal for inhalation. When Cayston came out the doctor felt I should give it a try and I did. It did nothing for me. Meaning no improvements in pfts. So when she mentioned the new drug, I said NO at this point I feel I am stable and there is nothing that is going to give me such a turn around I will be able to run. When people mention running marathons, I say WOW that's great. I use o2 at night. I'm also considered a mild case. I suffer from stress and depression as well, but at 60 what more am I going to do? I am just happy to have a BM everyday, as there are days that it is all day which sucks. But it comes with the territory. I think about the young ones more than myself and how this may help them to lead a better life, and how the parents who have to take care of their children with this horrible disease will it benefit them. So for whoever it is helping I said great news.t I have to say this last, I just have to.... the price of it OMG a new drug and this happens often who will be able to afford this?? It drives me crazy. My last battle with a new drug and pricing something that really has helped me, was Pulmozyme I call it my liquid gold, have not had a plug for years, and that was a big problem the stuff was so so thick I had to sometimes pull it out of my mouth as it would only come up half way, UGG I'm not even sure why I'm sharing that. So think about yr decisions, weight the pros and cons something I never thought about when I was younger. But you know the old saying with age comes wisdom....xxxxxx

 

[franzie2984]

Katie low-if I had to pinpoint it I would say 26 or so. I'll PM you.

 

[Simba15]

If you don't need it, don't take it. These clinics want those of us with rare mutations to take things we don't need to observe the affects. I won't be guinea pig until I NEED the meds That's my two cents.

I've got my clinic visit coming up next week and am conflicted about starting Orkambi. I don't love the price (even though I won't bear the brunt of the price, I don't love making my self-insured employer pay), I'm nervous about possible side effects especially those involving the liver, and am little disappointed that it doesn't seem to be as effective as Kalydeco. My lung disease has been somewhat mild. I only do Tobi 2-3 months of the year usually during flare up in the winter, I've yet to be hospitalized for a pulmonary exacerbation, I cough and produce but it is rare for it to be any sort of disruptive. I'm still at the point that anyone that finds out I have CF is surprised (and I'm able to keep that group fairly small), outside of the time commitment for treatments I'm able participate in any activity I want, I even completed a 10k race last weekend at an 8:30 min/mile pace. I still have downs, I'm tired (was once told I nap at a level twice my age), I get depressed and stressed, I tend to catch many of the bugs going around and when caught they hit me fairly hard. But still, I'm just not sure if I'm ill enough to require/deserve/risk $250k in brand new treatment.

Irrationally, a part of me is afraid. If I don't take Orkambi, then I have a few more weapons on the shelf when things start to go south. I'll protect myself from being disappointed in a sub-optimal treatment. In general, I've never been super cutting edge or overly aggressive in treating my disease, but I am super compliant once I start a treatment (I've maybe missed 1 or 2 Vest/Neb sessions in the last year). So any thoughts? Any things I should discuss with my Clinic team (I've heard rumors my clinic isn't focusing on getting Orkambi to those with PFT over 70%)? Any tools you use when you are decided to start a new treatment? Any opinions on being aggressive with mild disease?

PS> On a re-read this post does feel like complaining about 'first world problems' and I'm glad I have the luxury of decent health. But that being said, the above concerns are still valid to me.

 

[MichaelL]

I have mutations that indicate a mild form of CF. I wasn't even diagnosed until I was 34. That said, my health has really deteriated over the last seven years. I have now been on disability for a few years and my life has changed a lot -- not in a good way. Considering your long-term health and maintaining the quality of life you currently enjoy should be a big part of your decision.

I think your health should be a more important factor in your decision than insurance concerns. I'm surprised a small company would self insure. That is generally better for large companies with a large risk pool.

I don't want to sound like I'm trivializing your decision. I have not had to make a decision on these new drugs because they aren't prescribed for my mutation combination. As such, I have not done much reading on the side effects and risks.

 

[ethan508]

Thanks for the responses. You have all given me a broader vision.

A point of clarification. My company is pretty big (10k+ employees) and our health care is handled by corporate HR who hires an insurance company to administer the program. I understand that having a third party administration leaves coporate blind to which treatments go to which employee which keeps corporate protected from health based discrimination claims. So I'm not specifically worried about my job. Like Aboveall mentioned, it is more of an issue of being a good steward of resources. I've seen so many of my peers laid off (about 50% at the plant I work in 6 years) that I understand there is a bottom line when it comes to payroll. I don't want to eat more into that payroll on a whim. Even if it doesn't hit me directly it will hit someone else (if it cut into the million dollar bonuses at the top of corporate governance I might not mind, but the cuts usually start at the bottom).

If Orkambi gave me energy, if I wasn't so tired all the time, that alone would be worth it to me. I get tired of being tired. However, I didn't read any of the study data that mentioned fatigue or even the perceived health of the participants.

The one piece of study evidence that does carry weight in my mind is the reduced exacerbations. If this drug could give me another 30+ years with the health I've enjoyed in my last thirty years, I'd take that in an instant. It is amazing how improvement is the ideal goal for treatment, but even a reduction in decline or even the risk of decline is very enticing. Oh to have that crystal ball.

I guess that leaves me doing my own n=1 study or waiting to hear enough positive anecdotes and clinical experience to buy down the risk. But where do those anecdotes and clinical experience come from if people like me don't try the drug? Who would have thought so much faith would be involved in medical science?

 

[Printer]

Ethan:

Given the risks, I would not go on it. You seem to understand business; run a cost benefit on using Orkambi.

Bill

 

[jricci]

I've got my clinic visit coming up next week and am conflicted about starting Orkambi. I don't love the price (even though I won't bear the brunt of the price, I don't love making my self-insured employer pay), I'm nervous about possible side effects especially those involving the liver, and am little disappointed that it doesn't seem to be as effective as Kalydeco. My lung disease has been somewhat mild. I only do Tobi 2-3 months of the year usually during flare up in the winter, I've yet to be hospitalized for a pulmonary exacerbation, I cough and produce but it is rare for it to be any sort of disruptive. I'm still at the point that anyone that finds out I have CF is surprised (and I'm able to keep that group fairly small), outside of the time commitment for treatments I'm able participate in any activity I want, I even completed a 10k race last weekend at an 8:30 min/mile pace. I still have downs, I'm tired (was once told I nap at a level twice my age), I get depressed and stressed, I tend to catch many of the bugs going around and when caught they hit me fairly hard. But still, I'm just not sure if I'm ill enough to require/deserve/risk $250k in brand new treatment.

Irrationally, a part of me is afraid. If I don't take Orkambi, then I have a few more weapons on the shelf when things start to go south. I'll protect myself from being disappointed in a sub-optimal treatment. In general, I've never been super cutting edge or overly aggressive in treating my disease, but I am super compliant once I start a treatment (I've maybe missed 1 or 2 Vest/Neb sessions in the last year). So any thoughts? Any things I should discuss with my Clinic team (I've heard rumors my clinic isn't focusing on getting Orkambi to those with PFT over 70%)? Any tools you use when you are decided to start a new treatment? Any opinions on being aggressive with mild disease?

PS> On a re-read this post does feel like complaining about 'first world problems' and I'm glad I have the luxury of decent health. But that being said, the above concerns are still valid to me.

Ethan,
As someone who has always been very cautious of drugs and their side effects, I can certainly understand your hesitation with starting a new drug. However as you make this decision, please keep in mind the safety profile of Orkambi. Compared to other drugs that CF patients are treated with, Orkambi’s risk of serious side effects is low. Orkambi has been associated with a less than a 1% chance of liver damage. Orkambi has proven to decrease exacerbations by 30-39%. By decreasing number of exacerbations, Orkambi is decreasing the exposure to drugs with a much more hazardous safety profile. Compare the potential adverse effects of the antibiotics we are prescribed with the potential adverse effects of Orkambi. Comparitively, the adverse effects of antibiotics are greatly increased in number, incidence, and severity. For example, Tobramycin’s adverse effects include kidney damage, inner ear damage, nerve damage, seizures, and the list goes on...

I couldn’t agree more with your statement that “It is amazing how improvement is the ideal goal for treatment, but even a reduction in decline or even the risk of decline is very enticing.”
It seems that some people are somewhat disheartened by the modest improvement Orkambi has shown in clinical trials compared to Kalydeco with gating mutations. In the 6 month trial, Orkambi increased FEV1 by about 2.6-4 percentage points. Think about this- there was an increase, however small, in pulmonary function in people with a progressive disease. And this increase was a result of the partial correction of the underlying defect. You have to remember that this was a short 6 month trial of this drug. Try to put the results into perspective with the long-term implications of slowed progression of a life threatening disease. Ultimately, progression of the disease is what CF patients succumb to. If increased stability is achieved and progression is slowed, years are added to lives.

Unfortunately CF progression is unpredictable. I have a “mild” mutation. At the age of 44, I have been lucky enough to have CF in the background for most of my life. CF began to take center stage the last few years and the quality of my life has been affected. Average CF decline of FEV1% predicted is a decrease of 1.5 to 2 percentage points per year. My progression had accelerated. I had a 17 point decrease in the last 3 years. This was prior to starting Klaydeco off-label this past November. Fortunately I was able to regain some of this lung function thanks to Kalydeco.

Good luck with your decision and please keep us updated.

 

[ethan508]

Clinic went well. It is nice to have doctors/professionals that you have a mutually respectful relationship with. They are pretty good about presenting information and allowing me to digest it in my own way. We decided that Orkambi is something that is 'right for me.' So now my nurse coordinator is working to get the prior authorization for my insurance. If successful in obtaining it, I'm going to try it for 3-6 months and see how it turns out. If I'm going to be doing an personal n=1 study, I suppose I should get myself a log figured out to track some quality of life metrics. My doctor said that the Orkambi studies did track quality of life but I haven't found them. Anyone have a link?

Otherwise I did drop a percentage on my PFTs (grrrr). Still waiting for OGTT and other blood work results.

 

[imported_Momto2]

Ethan, please let us know what happens. I've heard that insurance companies would probably not approve Orkambi for someone with an FEV1 above 90%, but other than that doctors statement, I have no real evidence to back that up.

 

[Ratatosk]

The questionnaire the doctor submitted to Vertex GPS only asked is if he's DDf508 and if the treatment is appropriate. There weren't any additional questions regarding FEV1, though the doctor did mention DS' lower pfts -- he still hasn't mastered them yet --- the last time that it would probably help him. I guess I look at it in terms of while ds still doesn't have a lot of symptoms; annual lung scans and sinus CTs show a progression in the disease. The purpose of the drug is to treat the underlying cause of the disease based on the mutation. Plus it's pretty scary when we see people who are active, the disease doesn't seem to be progressing and then BAM, the culture a bug, catch influenza.... I want to use whatever tools in the toolbox that are available to increase longevity and help delay the progression of the disease.

 

[ethan508]

My doctor mentioned that the studies were done for people with a FEV1 range of 40-90% so it might be harder to get prior authorization outside of those ranges. Essentially I'm 4% 'off label'.

 

[Aboveallislove]

My doctor mentioned that the studies were done for people with a FEV1 range of 40-90% so it might be harder to get prior authorization outside of those ranges. Essentially I'm 4% 'off label'.

ethan,
The label doesn't have any fev parameter, so you aren't off label at all. Vertex might prioritize those with lower fev for the assistance such that if you and a fifty percent came in the same day they'd first help the other one with the paperwork...but fev is not a label issue. An insurance company try to pull "not medically necessary" if fev is high, but that shouldn't fly given what the drug does and what the label says, but it might mean appeals for some.

This is the "label": ----------------------------INDICATIONS AND USAGE---------------------------

ORKAMBI is a combination of lumacaftor and ivacaftor, a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, indicated for the treatment of cystic fibrosis (CF) in patients age 12 years and older who are homozygous for the
F508del mutation in the CFTR gene. If the patient’s

genotype is unknown, an FDA-cleared CF mutation test should be used to detect
the presence of the
F508del mutation on both alleles of the CFTR gene. (1)
Limitations of Use
The efficacy and safety of ORKAMBI have not been established in patients
with CF other than those homozygous for the
F508del mutation. (1)

http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206038Orig1s000lbl.pdf

 

[Brandon Justice]

I'm delta F508 homozygous, I'm 20 years old with an FEV1 of 89% and it's all thanks to Orkambi. I've been on the drug for 2 years through its clinical trial phase. Trust me everyone, it's a miracle. Diet and exercise and certain health and wellness products along with Orkambi is key to your success. Take a second to run past my blog brandoncysticfibrosis.wordpress.com I started it yesterday so folks who are interested can track my journey and know that Orkambi not only works, it blew away all of my expectations.

 

[ethan508]

My insurance decline the first authorization for Orkambi. They want an orignial copy of a genetic test to prove I'm really DDF508. My genetic test was done in 1997 as a part of a study by an universty hospital back east. My doctors only have a memo from the study hospital. So I guess I get to do another genetic test (no big deal but just more waiting time). I hope my insurance company will pay for the genetic test.