Thomas Werfel, MD, on the Safety of Tralokinumab for the Treatment of Atopic Dermatitis

Pooled data from 5 pivotal trials, which included 2285 patients, showed that tralokinumab was both safe and effective for patients with atopic dermatitis (AD).^1-4 

Researchers presented their findings at the European Academy of Dermatology and Venerology Virtual Congress. Overall, tralokinumab had a similar safety profile compared with placebo after 16 weeks of treatment and remained consistent through 52 weeks of treatment, they said.¹ The majority of adverse events (AEs) were mild or moderate in intensity, and serious AEs were found to occur at a lower frequency among the tralokinumab group compared with the placebo group (2.1% vs 2.8%, respectively). In addition, the most common AE associated with treatment was conjunctivitis, with researchers reporting increased incidence among patients with severe AD and among those with a prior history of allergic conjunctivitis.²

An exploratory analysis also showed tralokinumab was associated with significant reductions in Staphylococcus aureus colonization compared with placebo, with a 10-fold greater reduction among those treated with the interleukin (IL)-13 inhibitor compared with placebo.³ In addition, phase 2b trial data showed tralokinumab did not impact vaccine responses among patients who received diphtheria, tetanus, and pertussis (Tdap) and meningococcal vaccines.⁴

Corresponding author Thomas Werfel, MD, head of research with the Immunodermatology and Allergy Division and deputy director of the Clinical Department of Dermatology and Allergy at Hannover Medical University in Hannover, Germany, discussed these findings further in an interview with the Autoimmune Learning Network.

AUTOIMMUNE LEARNING NETWORK: Could you briefly outline your study design and some of the results? 

Thomas Werfel: The study was a pooled analysis of placebo-controlled trials of tralokinumab in order to increase the number of patients in the analysis. With this, it was possible to compare the frequency of AEs on a greater basis.

In terms of safety, tralokinumab was found to be very safe. There was just one AE that appeared more frequently in the treatment group compared with the placebo group, and this was conjunctivitis, or ocular or periocular inflammation. This AE is something we are already familiar with from other therapies that target IL-13 or IL-4. 

We also performed two substudies that addressed the rate of S aureus, which used data from only one of the placebo-controlled trials where the colonization rates of S aureus on the skin was assessed. The other was a prospective study that compared vaccination responses between the tralokinumab and placebo groups.

ALN: In terms of safety, this therapy was comparable to placebo, aside from the increased incidence of conjunctivitis. Could you elaborate more on the significance of the safety data and how it will affect the role of this therapy as a new option for AD?

TW: Safety is a big issue when we talk about novel systemic treatments in AD, because AD is a chronic skin disease that is not life-threatening but leads to a substantial reduction in quality of life.

There is a high need for efficacious treatment. On the other hand, we always have to be aware that novel treatments must be safe because the disease in itself is not life-threatening. Valid data on safety are very important for new treatment options in AD.

In our study, we did not observe any systemic AEs, nor did we observe any increases in infections or effects on the immune system, which some might perhaps speculate when a therapy interferes with this mechanism. There was no signature, aside from the local effect of conjunctivitis, in regard to safety, which is an important point.

Also, many patients with AD are usually young. While new therapies are approved for adults first, and safety among adults is important, safety is perhaps more prominent when reviewing new options for children and adolescents

ALN: Why did you decide to assess the impact of this therapy on S aureus colonization, as well as the vaccines, in your study?

TW: S aureus is often found in AD lesions. Treating the skin lesions usually leads to a reduction in the colonization of S aureus on the skin. There are many studies, and we also contributed to this knowledge in the last 20 years, that S aureus secretes products that may worsen the skin disease. 

Thus, a reduction of S aureus is an indicator of an efficient treatment of AD. It is more difficult for S aureus to survive on the skin surface when the skin barrier recovers. This was one reason why we chose to assess this outcome. The other, as I mentioned, is the concept that S aureus itself may drive the disease in a negative way. 

It was important for us to assess vaccination because whenever patients are treated with therapies that interfere with the immune system, we have to check in vivo in humans if this may have a negative impact on immune responses. The most straightforward way of doing this is to look at vaccination responses because these are T–cell-driven responses. This can be very easily and efficiently checked. It is also clinically relevant because vaccinations are, of course, very important, and it is important to know if a new therapy interferes with vaccination responses in a negative way.

In the study, it was clearly shown that treatment with tralokinumab does not interfere with positive responses to Tdap or meningococcal vaccination. This adds to the evidence that tralokinzumab is safe. 

While adults were studied because this is an early phase of clinical development for this particular therapy, it is intended to be studied and used to treat younger patients, so the issue of safety is of particular importance.

References:

1. Simpson E, Merola JF, Silverberg JI, Zachariae R, Olsen CK, Wollenberg A. Safety of specifically targeting interleukin-13 with tralokinumab in adult patients with moderate-to-severe atopic dermatitis: pooled analysis of five randomised, double-blind, placebo-controlled phase 3 and phase 2 trials. Presented at: European Academy of Dermatology and Venereology Virtual Congress; October 29-31, 2020; virtual.  

2. Wollenberg A, Beck LA, de Bruin Weller M, Zachariae R, Olsen CK, Thyssen JP. Conjunctivitis in tralokinumab-treated adult patients with moderate-to-severe atopic dermatitis: pooled results from five clinical trials. Presented at: European Academy of Dermatology and Venereology Virtual Congress; October 29-31, 2020; virtual.  

3. Bieber T, Beck LA, Pink A, et al. Impact of targeting interleukin-13 on Staphylococcus aureus colonisation: results from a phase 3, randomised, double-blind, placebo-controlled trial with tralokinumab in adult patients with atopic dermatitis. Presented at: European Academy of Dermatology and Venereology Virtual Congress; October 29-31, 2020; virtual.  

4. Merola J, Bagel J, Almgren P, Røepke M, Grewal P. Vaccine antibody responses in tralokinumab-treated adult patients with moderate-to-severe atopic dermatitis: results from the 30-week phase 2 ECZTRA 5 trial. Presented at: European Academy of Dermatology and Venereology Virtual Congress; October 29-31, 2020; virtual.