Trikafta and the identity crisis

By Jaquelien Noordhoek. M.A., M.Sc. President and CEO of the Dutch Cystic Fibrosis Foundation, President of Cystic Fibrosis Europe and President of the European Cystic Fibrosis Congress 2022

Having been a part of the CF community for nearly three decades, I think I can safely say that these are really exciting times. Before the era of modulating therapies, we welcomed news about the most effective droplet size of inhaled antibiotics, presented at international conferences on CF. A lot of progress has been made and, thanks to improved treatments, the survival rate has increased. Treatment with an effective and evidence-based multidisciplinary approach has contributed to this. It is amazing what has been achieved thanks to the persistence of so many researchers, clinical doctors, and patient organizations around the world.

We then entered the era of modulating therapies and the news was, and still is, overwhelming, exciting, and encouraging. Access to these therapies is improving, but not fast enough. For now, it really depends on where you were born. A tragic fact in life, in my opinion. Unfortunately, we tend to forget this in the hype we know, but we'll have to face the facts: in many countries, Trikafta (called Kaftrio in Europe) will probably never be available for people with CF. Imagine the frustration parents, patients, and doctors feel when they surf the Internet and read about what is happening in the western part of the world.

Nonetheless, we have reached the Trikafta era. In many homes, champagne bottles were uncorked when the family member with CF was finally able to swallow the first dose of this miraculous medication. Photos of patients receiving their first dose have gone viral. My organization received nicely decorated cakes for successfully lobbying for reimbursement of this medication in the Netherlands. Doctors, parents and people living with the disease, we all have high expectations for this new drug. Indeed, the results of study after study are impressive. The personal testimonies on social media are amazing.

Meditating on the huge change that medication can have on a life, a family, and a future, I was initially a bit surprised when a number of patients reported specific side effects to me. I'm not talking about the kind of side effects that are a result of the medication itself, such as the dose, the interaction with other medications, or the effects on mental well-being because of certain compounds in the medication. These types of effects are the subject of extensive studies. Here, I want to focus on the mental thoughts that people with CF and their loved ones may have when Trikafta is within reach, especially thoughts and feelings that are likely to exist but are not always planned or experienced consciously. However, they have a huge impact.

While preparing a presentation for the European CF conference last June, I asked a group of Dutch patients and parents of children with CF what they thought when Trikafta was at hand. As I said, I was a bit surprised by some of the answers, but they make a lot of sense when you take a closer look. In fact, some of their answers were eye-opening.

“I would like to know more about how Trikafta affects your life,” said a young woman with CF. Then she hastens to convince us how lucky she is to have access to this medication: “It's such a huge gift that I feel like I shouldn't be complaining or asking for understanding.” She has doubts and questions, but it seems she doesn't want to bother us with that, because the gift is such a beautiful thing. Another patient replied, “The people around me are so ecstatic about this; I'm afraid I won't be able to live up to their expectations. What if my body let me down? ”

I totally understand that. I understand that very well. People with CF grew up with the idea of not living very old. They had to get used to their bodies letting them down — or they had to adapt to it, physically and mentally. Parents raised their children with the fear of losing them, a thought that is always on the mind. These parents may now want to change their mindset, which seems easy to do, because Trikafta is so promising and the results are truly amazing. But see how this parent describes the change: “We lived 20 years with the idea that she wouldn't get old. Now that this could happen, we started to realize how worried we had been. For years and years. Only now do we feel the weight that has been on our shoulders for so many years. All of a sudden, we became aware of it. It was so sad and upsetting. This caused depression in one of us and some slight relationship problems, as we seemed to deal with it differently and we had to figure it out ourselves.” People with CF tend to rehash old worries and feel sorry for the painful episodes they had to endure in the past — at least that's what some people on the Dutch panel answered when asked.

Let's look at this a bit more. By talking to people with CF, they made it clear to me that they also need to get used to their “new” bodies. Maybe it's the same feeling people feel after a lung transplant. They were used to a body with limitations, pains, and very uncomfortable moments. Frustrations too. Now, that same body needs to be explored again and expectations are high: a whole new future seems to be in store for them. The same goes for mental processes when people with CF have access to Trikafta. This is not a side effect of the drug itself, but the brain has to adapt to a new and unpredictable situation. As glorious as the effects of drugs on the body are, mental processes will also be affected. New questions are emerging. Some panelists tell us that for the first time in their lives, they feel like they have a future. However, they are not at ease, they are not used to considering it. “Are you starting to make plans? ” we asked. “Or are you changing the plans you had?” Are you rethinking your future? “No, it's too early for that,” answered some people with CF, “but it seems that people around me expect me to make plans and create my own future with enthusiasm and eagerness, and their expectations are high and I am afraid of failure.”

“My life has another chance. And what do I do now? ” posted a woman with CF on Facebook. “Now that there is a possibility that I will get old [...] what kind of work should I like? I mean, think of something that I would like to do for many years. I just can't imagine it.”

The (possible) use of Trikafta makes people aware that too many people with CF did not survive. There are dear friends for whom the medication came too late. “Thinking of these people, I feel even more grateful and I also have feelings of sorrow again. [...] I wish they could have had the chance to experience the benefits of Trikafta.” There are also people with CF who do not have the “right” mutations and who cannot yet benefit from the medication. I'm still quoting an excerpt from a Facebook message: “I know they're happy for us, but it's sad that there's nothing for them.”

Most of the people on our panel answered that they had started to think differently about their future, and in a more positive way. They start dreaming of working, having children, participating in society, and feeling more confident because their illness now seems to be more of a chronic condition. At the same time, some people are worried about the possible side effects of the medication itself in the long term; some of them also experience feelings of anxiety upon realizing that they are dependent on the medication. What will happen if the medication cannot be prescribed or dispensed for any reason?

Another question that has been raised concerns the meaning of the term “severity of the disease” when the diagnosis should be discussed with parents of newborns. Life expectancy is much better today and more newly diagnosed children will be able to live their lives in more or less healthy conditions. The message of health professionals about CF has a huge impact on how parents perceive it; it affects their mental well-being and probably how they raise their children. So what is the best approach to describe the impact of CF on the lives of parents of newborns with CF? I invite health professionals to think about the possible effects of their message, when describing the impact of the disease and explaining the difference it can make if a person is eligible for and has access to the medication.

I want to thank the interviewees for giving us a better understanding of the effects that using this medication can have on their mental well-being. As involved bystanders, we need to know that possible side effects are not always obvious. And that is completely understandable.

“But when all of these thoughts go away, I feel thankful. So deeply, I can't explain it. I think it's because there were several occasions in my life where we thought “that's it” and then that sliding scale down. Or even the times when we had to deal with death. And I am always there. Life has been and is not over with me, of course.*”

*Quoted with the kind permission of Yvonne Verschoor-Broeksma.

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