Overview

Interferon (IFN) therapy was first approved back in the 1980s. This treatment modality uses artificial IFNs to treat certain viral infections, cancers, and autoimmune diseases. IFNs are signalling proteins, which are normally produced naturally by our body. These proteins play a significant role in your body’s immune response against combatting infection and cancer. During their discovery, IFNs were considered a cornerstone within drug development due to their potential as a general anti-viral and anti-cancer drug. However, its precedence has declined over the years and it is no longer used as a first-line treatment.^1,2 

In this article, we will explain what IFN therapy is and its potential benefits and risks. Why is IFN therapy no longer the standard treatment? And does it still offer any benefits?

What are interferons?

IFNs are signalling proteins that belong to a larger family of molecules called cytokines. Cytokines play a significant role in your body’s natural defence system. They are secreted by immune cells and are important in regulating immunity, inflammation, and haematopoiesis. These proteins act as chemical messengers to alert your body when something is wrong and activate your body’s immune response. This involves triggering immune cells through signalling cascades to attack invading viruses. IFNs are especially important in combatting viral infection and cancer. The name “interferon” was derived from its ability to “interfere” with the replication of viruses and cancer cells.

IFN therapy refers to the use of artificial IFNs that work similarly to the natural IFNs made by your body. The first IFN drug was approved by the U.S. Food and Drug Administration (FDA) in 1986 as an adjuvant treatment to treat chronic hepatitis and rare forms of cancer such as hairy cell leukaemia. 

Currently, IFN therapy is no longer the mainstay of treatment for these conditions. This is due to advancements in more targeted therapies, which have paved the way for more effective treatments that have less severe side effects. However, IFN therapy may still be recommended as a combination therapy or as an adjuvant drug. Patients who do not respond well or are unable to use conventional therapies may be given IFN instead.^1,2  

Types of IFNs

IFNs are categorised into three main subtypes. These subtypes are based on their anti-viral activity in vitro (outside the body). 

• IFN-alpha
• IFN-beta
• IFN-gamma

Recently, a fourth IFN subtype has been discovered called IFN-lambda. However, more research is required to enable its approval for clinical use.³ 

How are IFN drugs administered?

IFN drugs are administered subcutaneously (injection into the subcutaneous fatty tissue under the skin). The type of IFN and dosage you are given depends on the condition you have.^1,2  

What conditions can interferons treat?

IFN-alpha

• Chronic hepatitis B and C
• Genital warts
• Hairy cell leukaemia (blood cell and bone marrow cancer)
• Kaposi sarcoma
• Malignant melanoma
• Non-Hodgkin’s lymphoma
• Renal cell carcinoma (a type of kidney cancer)¹

IFN-beta

• Multiple sclerosis (MS)¹

IFN-gamma

• Chronic granulomatous disease (CGD)¹

Potential side effects 

IFN-alpha

IFN-alpha may cause flu-like symptoms such as:¹

• Chills (shivering)
• Fever (high temperature)
• Headache
• Myalgia (muscle pain)
• Nausea 

Other adverse effects may include:¹

• Alopecia (hair loss)
• Autoimmune reactions/inflammation
• Erectile dysfunction
• Fatigue
• Loss of appetite
• Skin rashes 

IFN-beta

If you are taking IFN-beta therapy, you may experience flu-like symptoms within 2-8 hours of injection. These symptoms last for less than 24 hours and may include:¹

• Back pain
• Chills (shivering)
• Fever (high temperature)
• Headache
• Myalgia (muscle pain) 

IFN-gamma

IFN-gamma therapy may lead to the following symptoms:¹

• Arthralgia (joint pain)
• Autoimmune reactions/inflammation
• Back pain
• Chills (shivering)
• Diarrhoea and vomiting  
• Erythema (redness or discolouration) or tenderness around the injection site 
• Fatigue
• Fever (high temperature)
• Headache
• Myalgia (muscle pain)
• Nausea 
• Skin rashes
• Weight loss 

Toxicity and complications

In addition to the side effects listed (above), IFN therapy can increase your risk of other severe health issues, such as:

Eye disease

IFN therapy can cause or worsen retinopathy. Retinopathy refers to a disease of the retina. The reported incidence of developing IFN-induced retinopathy is widely variable and ranges from 18% to 86%. Research shows that a higher incidence is generally found in patients who are nonresponsive to IFN therapy. Other risk factors include:^4,5 

• Age (older adults have a higher risk)
• Diabetes (IFN therapy may worsen in patients who already have diabetic retinopathy)
• High blood pressure (hypertension) 

Lung issues

IFN-alpha can cause pulmonary toxicity (lung damage). If you have pre-existing lung disease (e.g., bronchitis or pneumonia) using IFN therapy is not recommended as it may exacerbate your condition. Consult your healthcare provider if you experience symptoms such as a persistent cough or shortness of breath, as this may be indicative of more serious lung issues and you may need to stop taking IFNs.¹

Mental health disorders

One of the reasons for the decrease in IFN therapy use is because of its association with neurological disorders. Patients undergoing this treatment are reported to develop depression or suicidal ideation.⁶

Thyroid disease

Treatment with IFN-alpha has been shown to increase your risk of thyroid dysfunction. Your thyroid gland is a small organ found in your neck which secretes thyroid hormones. These hormones play an essential role in the regulation of your metabolism, growth, and development.  Patients may experience symptoms of either an overactive thyroid (hyperthyroidism or thyrotoxicosis) or an underactive thyroid (hypothyroidism). To prevent this from manifesting or worsening, your thyroid hormone levels should be monitored frequently (at least every 3 months). If you already have uncontrolled thyroid disease (i.e., your condition is not well controlled with medicine), then it is not recommended for you to take IFN therapy.⁷

Heart issues

Patients taking IFN-alpha are at risk of cardiotoxicity. Symptoms may include high blood pressure and experiencing abnormal heart rhythms (arrhythmia).¹ 

What conditions can interferon therapy be repurposed for? 

When IFN therapy was first discovered, it was proposed as a general anti-viral and anti-cancer drug. The use of IFNs has decreased over the years due to the development of more effective and targeted therapies that confer fewer side effects.

Nevertheless, an increasing number of studies are being conducted to optimise IFN therapy and investigate its use for other conditions. For instance, IFNs are potential candidates for COVID-19 treatment and as an adjuvant for cancer immunotherapy.^8,9,10,11

Overall, IFN therapy is still a viable treatment option particularly when patients are nonresponsive or do not qualify for other treatments due to potential complications.

What treatments have replaced IFN therapy? 

Initially, IFN therapy was a mainstay of treatment for conditions such as chronic hepatitis and hairy cell leukaemia. However, the development of alternative treatments with improved efficacy and tolerability has resulted in the decline of IFN usage. 

Examples of treatments that have replaced IFN therapy are:

Direct-acting antiviral (DAA) drugs  

Historically, hepatitis C was treated by combination therapy. This included a weekly injection of IFN and taking daily ribavirin (a capsule or tablet). But now, DAA drugs (e.g., sofosbuvir and daclatasir) are used to treat hepatitis C infections. These new drugs are administered via oral tablets, making treatment easier and more accessible. Moreover, they have fewer side effects than IFNs and the treatment course is shorter (DAA drugs are taken for 8 to 12 weeks, whereas IFN was taken for 24 to 48 weeks.) DAA drugs are also reported to have a cure rate of more than 90%, making it the favourable treatment modality for hepatitis C.¹²

Targeted therapies for cancer

In cancer treatment, IFN therapy has also been largely replaced by novel targeted therapies and immunotherapy drugs. As these drugs are more targeted, they have less off-target side effects, making them more tolerable and effective. Examples of targeted treatments include:¹¹

• Monoclonal antibodies
• Tyrosine kinase inhibitors
• Immune checkpoint inhibitors

Summary

IFNs are signalling proteins that activate immune cells through various signalling cascades. Activation of immune cells enables our immune system to fight disease and prevent the replication of viruses and cancer cells. IFN therapy refers to the medical treatment that utilises man-made versions of these IFNs. This therapy is used to treat certain cancers and viruses like hepatitis and hairy cell leukaemia. Although this treatment initially garnered a lot of attention and promise, in recent years more targeted and effective drugs have replaced IFN therapy. That said, IFN therapy is still an option for some patients and can still be beneficial for boosting your immune system. It also has potential applications for other conditions like COVID-19 and may be useful for combination therapies.