Tralokinumab shows promise for AD
The human monoclonal antibody tralokinumab significantly reduced skin colonization by Staphylococcus aureus (S. aureus) in adults with moderate-to-severe atopic dermatitis (AD), according to a study presented at ISDS 2018.
This phase IIb exploratory analysis comprised 204 participants who were randomized 1:1:1:1 to receive tralokinumab (45, 150, or 300 mg) or placebo every 2 weeks for 12 weeks on a topical corticosteroid (TCS) background. Lesional and non-lesional skin swabs were obtained at baseline and week 12 to identify S. aureus-positive patients. [ISDS 2018, abstract 96]
More than half of the population in each arm were S. aureus-positive at baseline (68.0, 74.0, and 67.3 percent for tralokinumab 45, 150, or 300 mg, respectively, and 74.5 percent for placebo).
At week 12, evaluation of lesional skin swabs revealed a significant reduction in the percentage of S. aureus-positive patients with all tralokinumab doses vs placebo, with percentage differences of -31.6 percent (p=0.002), -36.4 percent (p<0.001), and -38.3 percent (p<0.001) for tralokinumab 45, 150, and 300 mg, respectively.
There was a higher fraction of individuals who transitioned from being S. aureus positive at baseline to S. aureus negative at week 12 with all tralokinumab doses vs placebo (36.2, 40.8, and 43.8 percent for tralokinumab 45, 150, and 300 mg, respectively, vs 14.9 percent).
The findings suggest that combining tralokinumab with TCS resulted in a substantial reduction in S. aureus colonization over placebo, with the greatest improvement in the tralokinumab 300 mg arm.
“AD flares are associated with increased S. aureus colonization, which may amplify cutaneous inflammatory responses via release of staphylococcal super-antigens and toxins … [Our findings] suggest that specific neutralization of interleukin-13 with tralokinumab reduces S. aureus colonization, potentially leading to fewer skin infections and AD flares,” said the researchers.
Reduced disease burden
Using the same cohort, another evaluation reflected higher SF-36v2* scores for overall MCS** and PCS*** with tralokinumab 300 mg, suggesting improved health-related quality of life (HRQoL). [ISDS 2018, abstract 97]
Compared with placebo, mean change from baseline in SF-36v2 with tralokinumab 300 mg was 5.41 vs 1.18 for MCS (adjusted mean difference [adjMD], 4.23, 95 percent confidence interval [CI], 0.98–7.47; p=0.011) and 4.05 vs -0.21 for PCS (adjMD, 4.26, 95 percent CI, 1.83–6.69; p<0.001) at week 12.
Significant differences were also observed in all remaining domains except one – bodily pain (p=0.001), general health (p=0.014), physical functioning (p=0.031), role-physical (p=0.002), role-emotional (p=0.007), social functioning (p=0.003), and vitality (p=0.013); mental health improved but not significantly (p=0.079).
The minimal important difference was met with tralokinumab in nine domains ie, MCS, PCS, bodily pain, general health, mental health, role-physical, role-emotional, social functioning, and vitality (adjMD, 4.23, 4.26, 6.06, 3.42, 3.09, 4.82, 4.75, 5.23, and 4.08, respectively).
“[The HRQoL findings] suggest significant reduction in disease burden,” said the researchers.
No safety concerns
Approximately 150 tralokinumab and 51 placebo recipients from the same cohort underwent evaluation for anaphylactic events, hypersensitivity reactions, and antidrug antibody (ADA) development, which are considerations for any biologic substance. [ISDS 2018, abstract 95]
No anaphylaxis or severe hypersensitivity reactions associated with tralokinumab were identified. Only one tralokinumab 300 mg recipient developed ADA at week 22. “[However,] the ADA titre was low, with no impact on tralokinumab pharmacokinetics,” said the researchers.
Despite reports of eye disorders in all arms (6, 14, 0, and 6 percent for tralokinumab 45, 150, 300 mg, and placebo, respectively), all were non-serious and not treatment-related. There was only one report of treatment discontinuation (tralokinumab 150 mg) due to keratitis.
In AD, a further issue is the possibility of unexplained conjunctivitis, the researchers pointed out. Nonetheless, the findings revealed no differences in the risk of conjunctivitis with tralokinumab vs placebo (3 percent vs 4 percent), as well as keratitis (1 percent vs 0 percent) or all eye disorders (7 percent vs 6 percent).
Taken together, these results suggest that tralokinumab is relatively safe for patients with moderate-to-severe AD, said the researchers.