Nemolizumab: New Effective Drug for Management of Atopic Dermatitis, Study Finds

The trial report published in The Lancet Journal, suggests Nemolizumab
when used in combination with TCS and TCI has shown to be effective and there have
been significant clinical improvements in reducing inflammation and itch in
both adults and adolescents with moderate-to-severe atopic dermatitis.

Atopic dermatitis is a chronic, itchy inflammatory
skin disease commonly affecting children resulting in significant morbidity and
greatly affecting the quality of life. Nemolizumab, an interleukin (IL)-31 receptor inhibitor has recently been
introduced to manage atopic dermatitis, and a phase 3 clinical trial was
conducted to assess its efficacy and safety.

For this purpose, Jonathan I Silverberg, Department of
Dermatology, George Washington University School of Medicine and Health Sciences,
Washington, DC, USA, and colleagues organized ARCADIA
1 and ARCADIA 2, a double-blind, placebo-controlled phase 3 trials in
adult and adolescent participants, aged ≥12 years with moderate-to-severe
atopic dermatitis, associated pruritus, and inadequate response to topical
steroids.

Participants from 281 clinics, hospitals, and academic
centers in 22 countries were enrolled in both trials. They were randomly
assigned in a 2:1 ratio to receive either nemolizumab 30 mg subcutaneously
(with a baseline loading dose of 60 mg) or a matching placebo every 4 weeks.
This treatment was given alongside background topical corticosteroids (TCS)
with or without topical calcineurin inhibitors (TCI).

Both study staff and participants were blinded
throughout the study, with outcome assessors remaining blinded until the
database was locked. Coprimary endpoints at week 16 post-baseline were Investigator’s
Global Assessment (IGA) success (score of 0 [clear skin] or 1 [almost clear
skin] with a ≥2-point improvement from baseline) and at least 75% improvement
in Eczema Area and Severity Index score from baseline (EASI-75 response).

Outcome rates were compared between groups with
the Cochran–Mantel–Haenszel test adjusting for randomisation strata.

Efficacy analyses were done on
an intention-to-treat basis; safety analyses included all participants who
received one dose of nemolizumab or placebo.

The study reveals the following
findings:

• Both trials achieved the co-primary endpoints.
  At week 16, a higher proportion of participants receiving nemolizumab plus
  TCS–TCI achieved IGA success compared to those receiving placebo plus TCS–TCI
  (ARCADIA 1: 221 [36%] of 620 vs 79 [25%] of 321, with an adjusted percentage
  difference of 11.5%, ARCADIA 2: 197 [38%] of
  522 vs 69 [26%] of 265, adjusted difference 12·2%)
• EASI-75 response (ARCADIA 1: 270 [44%] vs 93
  [29%], adjusted difference 14·9%, ARCADIA 2: 220 [42%] vs 80
  [30%], adjusted difference 12·5%)
• Nemolizumab demonstrated significant benefits
  across all key secondary endpoints, including itch improvement as early as week
  1 and sleep improvement by week 16.
• The safety profile was similar between nemolizumab plus
  TCS–TCI and placebo plus TCS–TCI.
• 306 participants in ARCADIA 1 and 215 participants
  ARCADIA 2 who received nemolizumab plus TCS–TCI had at least one
  treatment-emergent adverse event.
• 146 participants in ARCADIA 1 and 117 participants
  ARCADIA 2 who received placebo plus TCS–TCI had at least one treatment-emergent
  adverse event.
• In
  ARCADIA 2, ten serious treatment-emergent adverse events potentially related to
  nemolizumab were reported in five (1%) participants. No deaths were reported.

“Nemolizumab demonstrates improvements in inflammation
and itch in adults and adolescents with moderate-to-severe atopic dermatitis. If approved, nemolizumab could
provide a valuable addition to existing therapies,” said the researchers.

Reference: Silverberg JI, Wollenberg A, Reich A, Thaçi D,
Legat FJ, Papp KA, Stein Gold L, Bouaziz JD, Pink AE, Carrascosa JM, Rewerska
B, Szepietowski JC, Krasowska D, Havlíčková B, Kalowska M, Magnolo N, Pauser S,
Nami N, Sauder MB, Jain V, Padlewska K, Cheong SY, Fleuranceau Morel P, Ulianov
L, Piketty C; ARCADIA 1 and ARCADIA 2 Study Investigators. Nemolizumab with
concomitant topical therapy in adolescents and adults with moderate-to-severe
atopic dermatitis (ARCADIA 1 and ARCADIA 2): results from two replicate,
double-blind, randomised controlled phase 3 trials. Lancet. 2024 Aug
3;404(10451):445-460. doi: 10.1016/S0140-6736(24)01203-0. Epub 2024 Jul 24.
PMID: 39067461.