Hopkins C, Surda P, Walker A, Wolf A, Speth M, Jacques T, et al. EPOS 4 patients. Rhinology. 2021 Suppl. 30: 1-57.

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Biologics

Why you have been prescribed this medication?

“Biologics” are medications that have been specially engineered to block the body’s pathways that generate inflammation.

Biologics can be tailored to target the exact path of inflammation for different diseases and so have been used in many different conditions – for example, they have been used for some time in rheumatoid arthritis and psoriasis. In addition, there are now biologics that can target the airway and in particular can be used for the treatment of asthma and chronic rhinosinusitis (CRS), especially in those with nasal polyps (CRSwNP).

 

CRS is an inflammatory disease. It is usually treated using medications such as intranasal steroids and saline irrigation. Usually, these treatments are successful in controlling the disease. However, despite appropriate medical treatment, CRS some- times fails to respond and surgery is usually offered as the next option. Again, surgery is successful in the majority of patients at improving symptoms and allowing access for nasal treatment that keep the sinus disease at bay. However, a very small minority of patients may have a relapse despite appropriate medical therapy and despite surgery. For CRSwNP, polyps may recur and up to 1 in 5 patients may need another operation within five years of their last. Until recently, this type of patient had few options other than to undergo repeated operations and / or courses of oral corticosteroids and they often suffered with a heavy burden of symptoms.

 

A new option for treatment

Biologic agents are a new option that can be added into these patient’s treatment plans. They are usually considered for patients whose chronic rhinosinusitis with nasal polyps do not respond to surgery and appropriate medical therapies. Some patients with sinus disease may also be considered for biologic treatment because they have asthma which is difficult to control. Interestingly, even though this specific treatment was originally designed primarily to treat asthma there are many patients who will also notice a significant improvement in their nasal symptoms.

 

The availability of biological agents vary across different countries, as does the selection criteria used to determine if biologicals can be used.

 

How biologic treatments work

Biologic therapies are a new type of medical treatment. These drugs directly act on your immune system by preventing the release of the chemical signals that trigger the body to respond by producing inflammation. In turn, there is a reduction in tis- sue swelling and it becomes less waterlogged. Polyps, if they are present, may stop growing or often significantly reduce in size. In turn, patients feel like they can breathe more easily through the nose, have less problematic nasal discharge, and may start being able to smell again.

 

Biologics are as effective as corticosteroids; both work to reduce inflammation but biologics do this in a more specific way so that there are fewer unwanted side effects. One of the most positive effects of biologic therapies is that they can reduce your reliance upon oral corticosteroids and can reduce the side effects associated with that medication.

 

Types of biologics

There are several different subtypes of biologic agents that can be used for sinus disease, and it is likely that the list will increase rapidly over the next few years now that the technology has been established. Dupilumab is the first agent we have that is targeted directly at nasal polyps and scientific trials have shown that patients using this treatment were found to have a significant reduction in the size of their polyps, and reported an improvement in their nasal breathing, sense of smell, and quality of life.

 

Other biologics named mepolizumab, reslizumab, benralizumab and omalizumab are available and are more often used for patients whose asthma is their number one medical concern. It is likely in time that many more biologic agents will become available.

 

How, when and for how long you should use it

Biologic treatment requires a series of injections. You will likely have some blood tests before receiving a biologic to help determine that they will be safe to use. 

If you receive dupilumab, the first injection will be performed by your doctor, but you may be able to perform them at home by yourself later on. Injections must be performed every 2 weeks and are usually continued long-term, but your doctor will be very clear about your exact treatment schedule.

 

If you receive omalizumab, the dose will be calculated precisely according to your weight. Injections must be performed every 2-4 weeks and again are usually continued long term – but your doctor will again be very clear on your exact treatment schedule also.

 

If at the end of your first trial period of the medication you have not found any benefit, you and your doctor may decide to dis- continue it. If you do notice an improvement, you will have the option to continue this treatment. Symptoms will be controlled as long as the treatment is maintained. Unfortunately, if you stop the treatment, symptoms usually return.

 

The availability of biologics may vary across different countries and are likely to change over time.

 

Side effects (and what to do if they occur)

Although side effects were reported in many of the trials for biologics, in most trials these were more common in patients who received a dummy or placebo injection, and biologics seem to be well tolerated in most patients. The most common side effects are injection site reactions (redness, swelling, itching), and a sore throat (nasopharyngitis). These side effects are usually short lived and settle without any medical treatment.

 

In a few patients, biologics can also cause serious side effects. Although these are very rare, you should be aware of their signs and if you notice them then you should immediately consult a doctor. First, these effects include allergic/hypersensitivity reaction such as uncontrollable itching, fever, skin rash, joint pain, swollen lymph nodes. The most serious form of these symptoms is called anaphylaxis which is recognised by very sudden onset of breathing problem, swelling of the face, mouth, tongue, and feeling very faint. If you have anaphylaxis symptoms: stop using your treatment and go to the emergency department of your nearest hospital right away.

 

Other reported side effects include eye problems such as a red, painful eye hair loss and joint pains, but these are also uncommon. As biologics are relatively new, there may be log-term side effects which have not yet been reported.

 

If you report other symptoms that are not listed in this leaflet and you think it may be related to your biologic treatment, you must also refer it to your physician.

 

Potential interactions with other medications you take Because biologics act on your immune system, you should be careful if you must be vaccinated. Notably, you should not receive a “live vaccine”, which are vaccines that contain fragments of active infection. At the time of writing, commonly used live vaccines include measles, mumps, rubella, vaccinia, varicella, zoster (which contains the same virus as varicella vaccine but in much higher amount), yellow fever, rotavirus, and some types of influenza. The first few coronavirus vaccines to have been discovered are not live – but you should always check the most up to date information.

 

Patient’s experience with biologics

Patient 1 reports:

“I was suffering from chronic rhinosinusitis with nasal polyps for more than 10 years. In addition to topical steroids, I was

prescribed several courses of prednisolone and already had two surgeries. Despite these treatments, my polyps came back and I was still suffering from sinusitis. One year ago, my physician told me about a new treatment, named dupilumab. He made the first injections, and then I was instructed about how to do it. After a few weeks, I felt an improvement: my sense of smell came back and I could breathe through the nose. My sleep gets better and my life has changed. I have encountered no adverse effect”

 

Patient 2 reports:

“I developed nasal polyps 5 years ago and took oral steroids twice a year to shrink my polyps. But they came back after few weeks. So, I had a surgery to remove them. But again, they came back. In addition, I suffer from asthma and it was some- times hard to control it. My ENT doctor and my lung specialist therefore prescribed me dupilumab. After the third injection, my polyps were gone. Now my asthma is controlled, my nasal breathing is normal and I enjoy smelling everyday odors! The only adverse effect I had was some itching on my calves”

 

Frequently asked questions

Can I just take biologics for 6 months and then see what happens?

Sinusitis with nasal polyps is a chronic disease. Therefore, it is recommended to take Dupixent as a long-term treatment. It you stop biologics after 6 months, your symptoms will probably recur; trials showed this happening within 8 weeks of the last injection If you are considering stopping biologics please meet with your physician first to discuss the reasons why, and any alternative treatments that may be considered. In some cases it might be possible to increase the interval between injections – in the trial of dupilumab, patients who were changed to 4 weekly injections after 6 months of treatment continued to achieve significant benefits.

 

Is it better to start biologics before surgery or afterwards to stop the polyps coming back, like with aspirin desensitisation?

Classically, biologics are indicated in patients with bilateral polyps who had had sinus surgery and who have uncontrolled disease despite surgery and systemic steroids treatment. If you never had surgery, surgery will most probably be proposed to you at first instance if your general health state allows, since it may adequately control your symptoms. If your symptoms are controlled after surgery, biologics are not indicated. If you relapse or feel no improvement at 3 months after surgery, biological treatment can be considered. Studies investigating specifically the combination of surgery and biologicals are on their way, and recommendations may change with time.

 

Will biologics stop me having reactions to alcohol?

There might be different causes why you react to alcohol, ranging from allergies to hyperreactivity. In both cases, treatment with bio- logics may reduce this reaction, however this has not been formally investigated and is therefore hard to predict. Notwithstanding, we suggest to keep your alcohol consumption moderate.

 

I have N-ERD – should I choose aspirin desensitisation, biologics or both?

If you have N-ERD, you may be indeed a candidate for both treatments, however, in general they are not initiated simultaneously. The decision between one or the other is up to you and your doctor. It depends on your clinical characteristics, medical history, existence of co-existing disease or potential contra-indications to one of these treatments. No study has compared both of these treatments, so after comprehensive review of your medical history, your physician will propose you the treatment best suited to your situation.

 

Which biologic should I choose?

Although there are several biologics, Dupixent and Xolair are the only monoclonal antibodies that are currently approved (as of Jan 2021) for the treatment of chronic rhinosinusitis with nasal polyps. If you have asthma, you may be given other biologics. We do not have any trials that directly compare different biologics yet, and there is no simple test to determine which is likely to give the best result or the lowest side effects. It is usually up to your doctor to decide which treatment is best suited to your personal situation, although some healthcare systems will have restrictions on what choice is available. If you do not respond the biologic you have been given, you may be switched to a different type, and in very rare cases, biologics may be used in combination.

 

What haven't I been offered a biologic?

Biologics are usually considered in patients with severe CRSwNP. They are not yet available in all countries. In other countries, they may only be available for people meeting certain criteria, or may have co-payment requirements. Your ENT surgeon is the best per- son to explain if a biologic is available and a good choice for your disease.