While Medytox and Daewoong have been embroiled in court matters over the source of a botulinum toxin (BTX) strain, from the consumer’s perspective, a growing issue of concern is resistance to BTX.

It is no secret that Korea has a large BTX market driven by its high emphasis on beauty standards. 

In North America and Europe, 60 percent account for treatment and 40 percent for beauty, whereas in Korea, the treatment and beauty market ratio is 10 to 90 percent. 

The Korean BTX beauty market is expected to grow from 173 billion won in 2021 to 209 billion won in 2023, according to Samsung Securities Research.

BTX uses a Clostridium botulinum toxin to reduce fine lines and wrinkles by paralyzing the underlying muscles. BTX is commonly applied to the forehead, between eyebrows, and eyelid wrinkles on the face. In Korea, BTX treatments for triangular jaws and shrinking trapezial muscles in the shoulders for wedding shoots are quite popular. It can also be used for excessive sweating, eyelid twitching, cervical dystonia, migraines, and post-stroke muscle stiffness.

An increasing BTX resistance trend

The treatments usually last for three to five months and should be repeated at regular intervals as prescribed by a clinician. 

However, repeated administration of BTX type-A (BoNT-A) can cause the formation of neutralizing antibodies that interfere with the biological activity of this BoNT-A protein, resulting in decreased therapeutic effect or immune resistance in severe cases.

According to a consumer study conducted by Merz Aesthetics and Frost & Sullivan between 2018 and 2021, 79 percent of respondents reported a decrease in the effectiveness of BTX treatment compared to the first time, a 10 percent increase compared to 2018.

A study published in June last year on the trends of BTX resistance showed that BTX resistance is growing due to the large amount of BTX administered during the treatment of neurological indications. 

Experts agree that using highly purified BTX preparations with a low risk of resistance is helpful to minimize the risk of forming neutralizing antibodies.

Additionally, the paper also emphasized the need to increase consumer awareness regarding resistance risk, noting that healthcare professionals should thoroughly discuss BTX treatments with patients in advance and get a thorough understanding of their BTX treatment history to recommend the right treatment.

Clinician guidelines for preventing BTX resistance

Many believe BTX resistance is linked to high doses or frequent BTX procedures.

However, Lift Plastic Surgery Director Jeon Su-gyeong pointed out that while patients who receive high doses might be more likely to show signs of resistance, even patients who receive small doses  with low frequency are not exempt.

“The amount of toxin you use will not solve the problem as it reacts differently to each person’s immune system,” said Jeon on a recent YouTube show.

She also observed that imported products appear to cause less resistance compared to domestic products due to the presence of a conjugated protein in Korean products.

Jeon explained, “It’s an issue of the purity of the products. When you extract toxins from bacteria, foreign substances, and complex proteins are usually attached to the toxins. Imported products tend to filter out these conjugated proteins but domestic products keep them, often resulting in more resistance.”

In this regard, she stressed the importance of a trained professional performing the procedure to first test the effectiveness of a BTX strain on a patient with a small quantity to evaluate how well the muscles are responding to the toxins. 

She elaborated, “Based on the response observed, the clinician can decide whether to increase the dosage to improve the effect or discontinue treatment if the patient has become resistant.

Accordingly, she advocated for using more refined BTX strains from the very first injection treatment if it can be afforded because once resistance develops, it is difficult to manage and unlikely for the person to respond to other strains.

Jeon also noted that while some Korean companies do manufacture refined BTX strains without the conjugated protein, they still add excipients called a sub-zero agent, at the end of the manufacturing process to ensure safe delivery which can sometimes affect the treatment.

Subsequently, the plastic surgeon mentioned three important factors to assess when picking a BTX strain -- the ingredients with a particular focus on the two aforementioned, the safety and sustainability of the product, and the possibility of developing resistance.

Company and consumer perspective on BTX resistance

Recently, Merz Aesthetics launched Xeomin domestically in Korea which can be maintained at room temperature and consequently, claims to have reduced resistance effects.

At Xeomin’s press conference in February, Apgujeong Oracle Dermatology Director Park Je-young said, “Xeomin isolates active neurotoxins through chromatographic techniques, a high-level manufacturing process that separates complex proteins that cause resistance.”

Meanwhile, Hope Wilson, a U.K. expat living in Korea, shared her experience of using BTX for four years inconsistently. “I have been slightly resistant to all the BTX I have tried so far as my muscles still move after treatment, but it is still 70 percent effective for me, but my American friend usually loses the muscle movement completely for about 2 months,” she recalled. “It is possible to build resistance to all types of BTX except Xeomin as it has fewer additives.”

In response to showing some signs of resistance, her doctor recommended trying a more expensive BTX treatment or waiting longer between injections.

However, she expressed that the value of BTX comes from the expertise of doctors rather than the product itself. She revealed, “I often revisit hospitals with friendly staff and experienced doctors as they can clearly see that I still have strong muscles and know exactly where they should inject the toxin for maximum effect.”