Wednesday, September 2, 2015

An update about IPF Treatment Guidelines

You might have heard that there are new “treatment guidelines” for Idiopathic Pulmonary Fibrosis (known as “IPF”). I was part of a webinar hosted by the Pulmonary Fibrosis Foundation last month where we summarized the new guidelines. Check it out.

If you have IPF, I think it is important for you to understand which treatments are currently recommended for IPF — and to also understand which treatments are not recommended for IPF. Before I begin, remember that everything on this website is informational in nature — please do not interpret anything I say as medical advice. Discuss everything with your doctor first before you make any changes to your medical treatment regimen. Also, you should be aware that these guidelines were only developed for folks with IPF. These guidelines do not apply to people with other forms of interstitial lung disease or pulmonary fibrosis.



In the next 4 paragraphs, I give a little bit of background about the guidelines. If you just want to skip ahead to the actual guidelines, scroll down to “Here’s what’s in the guidelines"

Clinical practice guidelines (typically just called “guidelines”) are a collection of formal recommendations to guide the diagnosis, screening, and/or treatment of a medical condition. Sometimes guidelines are developed by professional medical societies and sometimes they are developed by governmental organizations. In this case, the guidelines were developed by 4 professional medical societies: the American Thoracic Society, the European Respiratory Society, the Japanese Respiratory Society, and the Latin-American Respiratory Society.

Here are two links: the new treatment guidelines from 2015, which are an update to previous guidelines from 2011. Many of the recommendations in the 2011 guidelines still stand. The new guidelines only addressed 10 recommendations and of these they left 2 recommendations unchanged. I will try to present a unified overview of the current recommendations (whether from 2015 or from 2011), but I will also mention when a recommendation was new or changed in 2015.

The final bit to know about before we talk about the actual recommendations made in the guidelines is that there are two kinds of recommendations: STRONG and CONDITIONAL (referred to as WEAK in the 2011 guidelines). Even though STRONG sounds very different from CONDITIONAL or WEAK, the truth is that they are quite similar. A STRONG recommendation means that almost everyone would want the treatment. A CONDITIONAL recommendation means that the majority would want the treatment.

I should also point out that the guidelines also make recommendations against certain treatments. A STRONG recommendation against a treatment would mean that almost no one would want that treatment. A CONDITIONAL recommendation against a treatment would mean that some people might still want that treatment, but that the majority would not.

Here’s what’s in the guidelines:

Here is what is currently recommended to treat IPF

STRONG Recommendations for the treatment of IPF (Almost everyone will want this)
1. Oxygen use (when medically indicated by low oxygen levels)
2. Lung transplantation (when medically indicated)

CONDITIONAL (or WEAK) Recommendations for the treatment of IPF (the majority of folks will want these)
1. Pirfenidone (Esbriet®)
2. Nintedanib (Ofev®)
3. Antacid therapy (such as Prilosec® or Pepcid®) even in the absence of symptoms
4. Pulmonary rehabilitation

There is also a CONDITIONAL recommendation to use steroids (like prednisone) during a severe sudden worsening (called an “acute exacerbation”). Most folks who have an acute exacerbation need to be hospitalized — this is often a serious event.

Of the above recommendations, the only change in 2015 were the recommendations for pirfenidone and nintedanib.

I think all of the above recommendations are good ones  — and in my own opinion, I don’t see any distinction between the “strength” of the STRONG and CONDITIONAL recommendations. These are all STRONG recommendations in my mind.

As I mentioned above, there are also recommendations against using certain treatments:

STRONG Recommendations against treatment in IPF (almost no one will want this)

1. Steroids (such as prednisone) unless an “acute exacerbation” develops (see above)
2. Steroids combined with azathioprine and N-acetylcysteine
3. Steroids combined with other drugs that act on the immune system
4. Anticoagulation with warfarin (coumadin) — please note that folks who need blood thinners like warfarin for a different condition, such as atrial fibrillation or blood clots, should stay on their blood thinner. This recommendation is only meant to recommend against using blood thinners to specifically treat IPF.
5. Other medications that aren’t typically used nowadays for IPF. They include:
    Imatinib
    Colchicine
    Cyclosporine
    Interferon gamma
    Ambrisentan
    Etancercept

CONDITIONAL (or WEAK) Recommendations against treatment in IPF (some people might still want these therapies)
1. N-acetylcysteine alone (NAC)
2. Mechanical ventilator (a breathing machine) if respiratory failure (lung failure) develops.
3. Treatment of pulmonary hypertension
4. Sildeanfil
5. Other medications that aren’t typically used nowadays for IPF. They include:
    Bosentan
    Macitentan

Again, I tend to lump the STRONG and CONDITIONAL recommendations here together. They are all STRONG recommendations in my mind.

I imagine there are still many questions about these guidelines. Go ahead and post your questions and I’ll do my best to answer.

28 comments :

  1. What about Cellcept as a treatment?

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    1. Hi Mary,

      Some folks who have forms of pulmonary fibrosis other than IPF are treated with Cellcept (the generic name is mycophenolate mofetil) -- these guidelines don't apply to folks with diseases other than IPF. The guidelines also do not address the role of Cellcept as a single drug treatment for IPF, but the guidelines do recommend against using prednisone combined with drugs that act on the immune system (like Cellcept). I recommend discussing this with your pulmonologist. I frequently use Cellcept to treat folks who have both inflammation and fibrosis in the lungs (but who don't have IPF).

      Dave Lederer

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    2. What about using serrapeptase along with NAC as an aid to treatment?

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    3. Serrapeptase cannot be effective in treating lung disease because enzymes are digested in the stomach and never reach the lungs.

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  2. Dr. Lederer, what is your feeling of pursuing a Nissan Fundoplication operation to stop GERD since PPI's like Nexium or Dexilant do not stop the reflux but only reduce the acid. It seems like the Nissan stops GERD while the drugs only tamper down the acid. What is your opinion?

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    1. Hi Bill. Good to see you here. This is one of the big questions in the field right now. You are 100% correct: Antacid therapy only reduces acid and does not stop reflux of "non-acid" liquid into the esophagus -- this non-acid liquid can contain bile, enzymes, and food particles, which could damage the lung. There is a surgical procedure (Nissen fundoplication) in which the surgeon wraps a part of the stomach around the lower part of the esophagus. This approach can be extremely effective in preventing reflux. You are probably aware that this strategy is being studied in IPF in a clinical trial sponsored by the National Institutes of Health (https://clinicaltrials.gov/ct2/show/NCT01982968). Until we have an answer, I do not routinely recommend this type of surgery for folks with IPF unless they have another reason to undergo this surgery.

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    2. Good day,

      I have ILD/ fibroses i am on 4L oxygen 24\7. I have realy bad reflux i cought alot cant eat anything then i start coughting up flem. I am on nexuim,rennies an citrozoda still have reflux. They say it is bad but whe cant fix it becuase my oxygen is to low its at 34%. I was on cellcept also did'nt work no cortizone is working. What else can i do to helo with reflux just stop coughting and having so much flem thanks so much dr

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    3. Thanks for sharing your story here. I don't think I can give you a straight answer based on your post here. I suggest talking to your pulmonologist and perhaps a gastroenterologist about how to best manage your symptoms. All the best.

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  3. I have not been able to tolerate either Esbriet or OFEV. When I was on these my cough increased dramatically. I was hospitalized after trying Esbriet for about 1 1/2 months. I'm taking 10mg Prednisone daily and my cough is under control. Could you please comment on this? I hate taking Prednisone for so long (4 yrs now), but it seems to be the only choice.
    Also I have a slow growth IPF I believe, as my pulmonologist says there has been little or no growth in the last 2-3 years. Or do I have IPF at all???

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    1. Hi Bob. Thanks for sharing your experience. I'm sorry to hear you've had such a hard time with these medications. I can't offer specific medical advice to you about prednisone or your diagnosis, but I will say that many people have improved cough with low doses of prednisone (likely due to decreased post-nasal drip, in my opinion). I suggest you discuss this with your doctor and see if there are other medications that might help -- take a look at my recent post about managing cough. I will point out that there is at least 1 clinical trial for folks with IPF who are not on Esbriet or OFEV. You can read more here: https://clinicaltrials.gov/ct2/show/NCT01890265. Good luck.

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  4. The Conditional Recommendations for treatment list both perfenidone and nintedanib. Do you prescribe these drugs in concert? If you prescribe one of these drugs with greater frequency, which one and why? I have been taking Esbriet for almost two years but am now considering a switch to OFEV. I would appreciate any insights that might help me with this decision. Thank you

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    1. Hi Jilly. Thanks for your questions. I am not aware of anyone who is prescribing both pirfenidone and nintedanib together for the same patient. There is one published study from Japan where a handful of folks with IPF were given both medications: http://erj.ersjournals.com/content/45/5/1382.

      I do not have a preference for one drug over the other. They each slow the decline in lung function by about 50% over time. In my experience, I have kept people on the same drug for as long as they have tolerated it. Best of luck.

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  5. My husband is on 3000 mg daily of Cellcept and 10 mg a day of Prednisone, it seems to be holding his fibrosis at bay. He is on 3 liters of 02 at rest and 8 liters with exertion. He has been diagnosed with Hypersensitivity pneumonitis/ILD from a pet bird, with ground glass opacity and honeycombing. I am worried now reading that you are strongly advising against the both of these drugs used. Why? What kind of side effects happens ?

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    1. Thank you for giving me the opportunity to clarify this. The current guidelines recommend against using prednisone and cellcept (also known as mycophenolate mofetil) to treat IPF. Based on what you shared, your husband does not have IPF. Instead, he has hypersensitivity pneumonitis -- a different type of interstitial lung disease (you may want to confirm this with your doctor since I don't have the details of your husband's medical condition). Prednisone and cellcept are used to treat inflammation in the lung, which is common in hypersensitivity pneumonitis but is uncommon in IPF. I frequently use prednisone and cellcept to treat hypersensitivity pneumonitis.

      Regarding side effects, here are some websites that provide information and side effects from prednisone:

      http://www.hopkinsvasculitis.org/vasculitis-treatments/prednisone/
      http://www.ucsfhealth.org/education/prednisone/.

      I also wrote about prednisone on my blog back in 2013:

      http://www.pfdoc.org/2013/11/should-i-take-prednisone-for-my.html

      Cellcept is generally well tolerated. In my experience, the major side effects are diarrhea, infection, and less commonly low blood cell counts. There are also risks to the fetus if a pregnant woman takes cellcept.

      Best of luck.

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  6. Thanks for this. I have used the saline nasal rinse and it seems to help. Still worried about the long term effects of prednisone, even in low doses. I'm on 10 mg/day now. PLease comment and thanks!

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  7. Hi Dr Lederer, my husband had IPF and a double lung transplant 8 months ago. He is doing fantastic for the most part. He developed a slight cough 2 months ago and the Dr's are sending him to a specialist for reflux. Does that sound typical?

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  8. Hi Terri. Thanks for sharing the good news about your husband. Great to hear that he is doing well. Yes, reflux is common after lung transplantation, and it is very common for folks to undergo reflux testing after lung transplantation. Please give your husband my best regards!

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  9. Dr. Lederer, why is there a recommendation against treating pulmonary hypertension in some patients?

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    1. Hi Nancy. Good question. Maybe I'll try to address this in an upcoming post in detail. Briefly, I can tell you that pulmonary hypertension (elevated blood pressures in the artery that connects the heart and the lungs inside the chest) should be treated when it is due to a problem in the blood vessels in the lung (called pulmonary arterial hypertension, or PAH) but should not routinely be treated when it results from heart disease or from a problem in the airways or airscas of the lung (such as IPF). This recommendation was made both by the guidelines I discuss above and by the ABIM Foundation's Choose Wisely campaign:

      http://www.choosingwisely.org/clinician-lists/american-college-chest-physicians-american-thoracic-society-pharmacologic-treatement-with-advanced-vasoactive-agents/

      The reasons for this are (1) some drugs that treat pulmonary hypertension are ineffective or even harmful in IPF (for example, ambrisentan), and (2) we haven't adequately studied how, when, and who to treat if a patient has both IPF and PH. Treatment might be helpful or harmful or neither. Some studies are ongoing to try to sort this out.

      At the very least, someone with IPF or PF who has PH should not initiate therapy for PH without consultation with a physician experienced in the care of people with PH. Also, anyone reading this should not change their therapy in response to reading this without discussing things with their physician.

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  10. I was diagnosed with IPF February, 2015. It took about 7 months of testing to figure it out. I have been very interested in rehab, but when my doc tried to set it up,I was told that I wasn't bad enough. I thought the idea was to not get bad enough through education.

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  12. I have of possibly caused by lupus. I have been taking cellcept. Should I continue this treatment?

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    1. I guess I missed this question -- sorry! This is a question you should discuss with your doctor. I cannot give you medical advice or make medical recommendations over the internet.

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  13. Dr. Lederer

    Has there been any change in your 2015 view on treating IPF? In Australia the chance of a Lung Transplant is near zero even with maximum health insurance

    Thank you
    Stephen

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    1. There are no new drugs approved since 2014 to treat IPF in the US, and many of the other therapies I recommend (oxygen, pulmonary rehabilitation, transplant) have not changed either. So, my approach is largely the same. There are some newer studies suggesting that antacid therapy may carry risks in IPF, so I often take that into account when making treatment recommendations.

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  14. Thank you for this blog! My name is Hannah. My mother and both maternal grandparents died of IPF--my grandparents both at age 84, and my mother last July at age 64. My mother's final diagnosis was Familial IPF, and I (female, age 38) want to do what I can to preserve lung function if I develop the disease. Are OFEV or Esbreit ever given or recommended for patients without IPF diagnosis but with a familial history? Also, I have been offered prednisone for acute viral infection of the lungs recently but declined because I don't tolerate the emotional side effects well--from reading this blog, it seems that declining prednisone is a good choice with our familial history of IPF (yes?). I can tolerate steroid shots and am on a QVAR inhaler--what does your research show about positive/negative effects of either of these forms of steroid for patients with IPF? Is long-term use of QVAR bad for IPF? Lastly (sorry for so many questions), we banked cord-blood stem cells for both our children when they were born--is there any recent news on stem cell research for IPF (thinking ahead for them)? Thank you!

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    1. Hi Hannah. Thanks for reaching out. I am sorry to hear about your mother and both of your grandparents. It is unusual for two unrelated family members to both develop PF (although I have seen this before). Sometimes that indicates some kind of exposure (such as mold or birds) that can trigger scarring in the lungs (http://www.everydayhealth.com/columns/health-answers/mold-and-a-misdiagnosis-that-could-leave-you-breathless/).

      There are no official medical guidelines on prevention of PF. We do not use either of the two approved anti-fibrotics to prevent PF. I can't really provide advice about oral or inhaled steroids -- best left up to your doctor (sorry). There are also no medical guidelines on inhaled steroids for people with PF. "Stem cell therapies" for PF advertised in the US and elsewhere are not proven to be effective and there are reports of serious adverse events after undergoing the procedure. These "treatment" are not covered by insurance because they are a scam.

      Things you can do: Have regular follow-up visits with your doctor, make sure he or she listens carefully to your lungs every time you get a physical exam, use hand sanitizer/soap to avoid infections, and follow your doctor's advice for a healthy diet and exercise.

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    2. Thank you so much for this reply! And especially for the preventative advice and for the information on stem cells. They suspected asbestos exposure for my grandfather (who was in construction) and grandmother (who washed his clothes), but when my mother also died of IPF so much younger than either of them, the familial piece came into the picture. She entered a study on familial IPF at Vanderbilt before she died--hopefully research on this form of IPF will yield more answers as time goes on. Thank you so much for all you and your research partners and practitioners are doing!

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