What Makes A Drug First-Line Or Second-Line?

Last updated: March 2020

So, a fellow asthma writer posed a question to me. She said, “What makes a drug a first-line versus a second-line option?" A great question. One worthy of a great answer. So, here is what I have to say on this topic.

What makes a drug first-line?

These are the medicines doctors first resort to for a given disease (the doctors first choice try). They are the most commonly prescribed medicines for a particular disease. These medicines are well accepted by the medical community.

For asthma, they include systemic corticosteroids like Flovent, Asmanex, and Qvar. They include combination inhalers like Advair, Symbicort, Dulera, and Breo. These medicines are the first choices doctors will prescribe when trying to help you obtain better asthma control. One or a combination of these will work for most asthmatics.

How is it decided what drugs are first-line vs second-line?

I couldn’t find any specific answer to this question among the literature I have access to. So, I am going to make an educated guess here. I’m going to speculate that there are five qualifications for a medicine becoming first-line.

  • It works. It opens airways fast. It helps you prevent symptoms and control your asthma. More importantly, it works for most people with asthma. Studies prove it works. Examples here include albuterol and Advair. They have both been well studied. They are proven safe and effective for asthma. Albuterol ends asthma attacks and Advair prevents them.
  • Side effects are minimal. You can tolerate or easily treat side effects if they occur. Side effects to albuterol and Advair are considered negligible. Both medicines may cause tremors, but it’s often considered a good trade-off for being able to breathe. Advair may cause thrush. But, it’s both preventable by rinsing and treatable.
  • It’s cost effective. Most people can afford it. Most people can afford a $50 copay for albuterol or Advair. They may not want to pay that much, but they can afford it.
  • It’s easy to administer. You can take it by yourself. Inhalers and nebulizers are easy to use. Most inhalers are generally simple to use. Modern nebulizer systems are easy for the general asthmatic to set up and use.
  • Doctors are comfortable prescribing it. They recognize that it will benefit you. They are confident it’s safe and effective. Most asthma experts recommend all asthmatics have a rescue inhaler like albuterol handy at all times. Most doctors are comfortable with this recommendation.

What makes a drug second-line?

These are your medicines that are less commonly prescribed for a particular disease. But, they are available as options when first-line treatments alone are not working.

What classifies a medicine as the second line?

Again, I’m going to speculate using experience guided by common sense. This is just a guess. But, I believe I am close to the actual answer, if not spot on. Again, there are five qualifications.

  • It’s not proven. It may work for some, but not all people with asthma. A good example here is Singular. It helps some asthmatics, but not all. Biologics like Xolair may also fit into this category. It’s a relatively new line of treatment. So, future studies may reveal it only helps some asthmatics.
  • There’s a greater risk for side effects. Systemic corticosteroids fit nicely into this category. They work great for ending asthma attacks and controlling asthma. But, the risk for side effects is too great. So, they sit as second-line treatments ready to be prescribed if and when needed.
  • It’s not cost effective. Xolair costs thousands of dollars. Because it costs so much, it’s reserved as a second-line option. At the present time, all biologics fit into this category.
  • It’s not easy to administer. Xolair needs to be injected into a vein. So, it’s not easy to give to yourself.
  • Doctors are not as comfortable with it. Xolair is a newer medicine. So, some doctors may be leary of it. This relegates it to second-line status. So, new medicines may fit into this category.

What causes a drug to change first-line or second-line status?

Or what causes first-line medicines to become the second-line? What causes second-line drugs to become first-line? Once again, I’m going to make an educated guess here.

  • Studies show it’s not as beneficial as once thought. Muscarinics are a good example here. Atrovent was once-upon-a-time considered a first-line asthma medicine. It fit all the qualifications of one. But, subsequent studies did not show it benefited most asthmatics. Studies do show, however, that it does help most COPDers. So, it remains a first-line treatment for COPD. Likewise, because it may help some asthmatics, it remains a second-line option here.
  • Researchers learn more. Back in the 1970s, doctors were leary that inhaled corticosteroids (ICS) may cause the same side effects as systemic corticosteroids. After studying this hard, researchers learned ICS are safe and effective for controlling asthma. This moved ICS out of second-line into the first-line status.
  • Better, stronger, safer medicinal options become available. A good example here is theophylline. It was a first-line asthma medicine during the 1970s and 80s. It opened airways and kept them open. But, it also had some unwanted side effects, such as it kept you awake, like coffee does. The advent of combination inhalers like Advair made it so most asthmatics could be weaned off theophylline. This helped to relegate Advair to first-line status. But, it moved theophylline from first-line to second-line drug status.

What to make of this?

So, these are just some examples of what makes a drug first-line or second-line? There may be other reasons overlooked here. Still, this should give you a pretty good idea of why that Advair inhaler is first-line and why Singular is second-line.

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