Dear Editor,
Real‐life data concerning dupilumab effectiveness and safety in adolescents (aged ≥ 12 to <18 years) with moderate to severe atopic dermatitis (AD) are rarely reported. 1 In two adolescence studies, the phase III randomized, placebo‐controlled, clinical trial (LIBERTY AD ADOL) 2 and the phase IIa and subsequent phase III open‐label extension (LIBERTY AD PED‐OLE) 3 dupilumab produced significant improvement in signs and symptoms at Week 16, with a good safety profile. We report our real‐life experience in using dupilumab to treat AD in adolescents.
This was a 32‐week prospective real‐life study. The study was approved by the ethics committees of the participating institutions, and informed consent from patients and parents were obtained.
Nine adolescents (mean age 15.7 years) with moderate to severe AD who were started on dupilumab from January to October 2020 under the Italian Medicine Agency compassionate use programme were included in this study. Data on demographics and AD clinical characteristics at baseline are reported in Table 1.
Table 1.
Demographics and clinical characteristics at baseline of nine adolescents with moderate to severe atopic dermatitis.
| Patient | Sex | Age, years | BMI | Age at AD onset, years | Clinical course | Atopic comorbidities | Prior systemic medications | Clinical phenotype | EASI | cDLQI | NRS itch score | NRS sleep‐loss score |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | F | 15 | 31.9 | 1 | P | – | AH, CsA, PT, SCS | DE | 42 | 28 | 9 | 8 |
| 2 | M | 17 | 22.2 | 1 | R | A, Rh | AH, CsA, PT, SCS | FE, HNE, HE | 26 | 21 | 7 | 6 |
| 3 | M | 14 | 25.6 | 2 | R | – | CsA, SCS | DE | 36 | 24 | 9 | 9 |
| 4 | M | 15 | 23.2 | 1 | R | A, C, Rh | AH, CsA, SCS | DE | 55 | 28 | 4 | 4 |
| 5 | M | 16 | 21.2 | 1 | P | A, Rh | CsA, SCS | DE | 36 | 30 | 9 | 9 |
| 6 | F | 16 | 22.0 | 5 | P | – | – | FE, HNE | 42 | 25 | 9 | 7 |
| 7 | F | 15 | 19.3 | 1 | R | – | AH, SCS | FE, HNE, HE | 27 | 8 | 7 | 6 |
| 8 | F | 16 | 28.6 | 2 | P | A | AH, PT, SCS | FE, HNE, HE | 24 | 5 | 9 | 8 |
| 9 | F | 17 | 25.1 | 12 | P | Rh | AH, CsA, SCS | DE | 30 | 25 | 9 | 8 |
A, asthma, AD, atopic dermatitis; AH antihistamines; C, conjunctivitis, cDLQI, Children’s Dermatology Life Quality Index; CsA. ciclosporin A; DE, diffuse eczema; EASI, Eczema Area and Severity Index; FE, flexural eczema, HE, hand eczema; HNE, head and neck eczema, NRS, Numerical Rating Scale; P, persistent, PT, phototherapy; R, relapsing; Rh, rhinitis; SCS, systemic corticosteroids.
Eight patients (weight ≥ 60 kg were treated every 2 weeks with dupilumab 300 mg) and the ninth (weight < 60 kg) with 200 mg. Moisturizers and mild topical corticosteroids (TCS) were allowed. AD characteristics, TCS use and adverse events (AEs) were assessed at Weeks 16 and 32.
All patients completed the full 32‐week course of dupilumab. At Weeks 16 and 32, 100% of patients reached 75% reduction in Eczema Area and Severity Index (EASI75), 44.4% reached EASI90 and 22.2% reached EASI100 (Table 2), with an EASI reduction at Weeks 16 and 32 of 84.7% and 83.0%, respectively. At Week 16, there was a 77.4% reduction in the Children's Dermatology Life Quality Index (cDLQI), which reduced from 20.4 to 4.6, a 5.9‐point reduction in Numerical Rating Scale (NRS) itch score (from 8.0 to 2.1) and an 87.5% reduction (from 7.2 to 0.9) in NRS sleep‐loss score. Overall, the therapeutic outcome was maintained at Week 32.
Table 2.
Dupilumab effectiveness at Weeks 16 and 32 by sex, baseline body mass index (< 25 and ≥ 25) and baseline Eczema Area and Severity Index (< 30 and ≥ 30).
| EASI reduction | All patients (n = 9) | Sex | Baseline BMI | Baseline EASI | |||
|---|---|---|---|---|---|---|---|
| Male (n = 4) | Female (n = 5) | BMI < 5 (n = 5) | BMI ≥ 25 (n = 4) | EASI < 30 (n = 3) | EASI ≥ 30 (n = 6) | ||
| Week 16, n (%) | |||||||
| EASI75 | 9 (100) | 4 (100) | 5 (100) | 5 (100) | 4 (100) | 3 (100) | 6 (100) |
| EASI90 | 4 (44.4) | 1 (25.0) | 3 (60.0) | 3 (60.0) | 1 (25.0) | 1 (33.3) | 3 (50.0) |
| EASI100 | 2 (22.2) | 0 | 2 (40.0) | 1 (20.0) | 0 | 1 (33.3) | 1 (16.7) |
| Week 32, n (%) | |||||||
| EASI75 | 9 (100) | 4 (100) | 5 (100) | 5 (100) | 4 (100) | 3 (100) | 6 (100) |
| EASI90 | 4 (44.4) | 2 (50.0) | 2 (40.0) | 4 (80.0) | 0 | 1 (33.3) | 3 (50.0) |
| EASI100 | 2 (22.2) | 0 | 2 (40.0) | 2 (40.0) | 0 | 1 (33.3) | 1 (16.7) |
BMI, body mass index; EASI, Eczema Area and Severity Index.
The two patients who reached EASI100 at Week 16 were both female. Adolescents with a body mass index (BMI) of < 25 were more likely than those with a BMI of ≥ 25 to achieve EASI90 or EASI100 at Weeks 16 and 32. Patients with EASI of ≥ 30 at baseline were more likely than those with baseline EASI < 30 to achieve EASI90 at Weeks 16 and 32 (Table 2).
All patients stopped TCS at a mean of 15.3 days (range 1–24 days) after the beginning of dupilumab therapy. One patient contracted asymptomatic SARS‐CoV‐2 infection at Week 10, and one developed mild conjunctivitis at Week 12 treated with dexamethasone ointment; both continued on dupilumab.
In this real‐life experience of adolescent AD treated with dupilumab, we documented an excellent therapeutic response with the drug, better than that reported in the 16‐week LIBERTY AD ADOL 2 and the 52‐week LIBERTY AD PED‐OLE 3 studies. In fact, all of our patients reached EASI75 at Week 16, compared with 41.5% 2 and 68.4% 3 of patients in the previous two trials. Similarly, 44.4% of our patients reached EASI90 compared with 23.2% 2 and 52.6 3 of the previous trials. Two of our patients (22.2%) achieved completely clear skin, compared with none of patients included in the previous trials. 2 , 3 Additionally, we observed a greater improvement in patients with low BMI and high EASI at baseline.
Other AD characteristics also presented a better outcome in our study compared with the two clinical trials: at Week 16 we observed a reduction from baseline in cDLQI score (77.4% vs. 64.9% 3 ), NRS itch score (5.9 vs. 3.6 2 and 5.0 3 points), and NRS sleep‐loss score (87.5% vs. 47.9% 2 ), and all of these meaningful improvements were maintained at Week 32, with a further decrease in NRS sleep‐loss score (giving a 94.4% reduction from baseline).
We confirmed the excellent tolerability and safety of dupilumab, even in the SARS‐CoV‐2 infected patient. The issue of dupilumab therapy was under debate during COVID‐19 pandemic first wave. 4 In the Italian experience on 1576 patients under dupilumab treatment, 15 patients contracted SARS‐CoV‐2 infection with a good clinical outcome, confirming that dupilumab should be continued during the COVID‐19 pandemic. 5 Nevertheless, systematic studies are needed to evaluate the effect of dupilumab in patients with SARS‐CoV‐2 infection.
Conflict of interest: KH has performed paid activities as a speaker for AbbVie and Celgene; CP has performed paid activities as a consultant, advisor or speaker for AbbVie, LEO Pharma, Pfizer, Novartis, Regeneron and Sanofi; MH has performed paid activities as a consultant, advisor or speaker for AbbVie and LEO Pharma; GF has performed paid activities as a consultant, advisor or speaker for AbbVie, Celgene, Janssen, LEO Pharma, Lilly, Novartis, Amgen, Almirall and Sanofi; TG has performed paid activities as a consultant, advisor or speaker for Sanofi, Eli Lilly and Novartis; GP has performed paid activities as a consultant, advisor or speaker for AbbVie, Almirall, Amgen, Celgene, Eli Lilly, Sanofi, LEO Pharma and Novartis; MNF has performed paid activities as a consultant, advisor or speaker for Almirall, LEO Pharma, Janssen, Novartis, Lilly, UCB, AbbVie, Amgen, Pierre Fabre, Galderma, Mylan, Medac Pharma, Roche, Sun Pharma MSD and Sanofi‐Genzyme; ME has performed paid activities as a consultant, advisor or speaker for AbbVie, Almirall, Biogen, Celgene, Eli Lilly, Janssen, LEO Pharma, Novartis, Sanofi Genzyme and UCB; VP has performed paid activities as a consultant, advisor or speaker for AbbVie and Sanofi; MZ has performed paid activities as a consultant, advisor or speaker for AbbVie, Sanofi and Novartis; GG has performed paid activities as a consultant, advisor or speaker for AbbVie, Abiogen, Almirall, Amgen, Biogen, Boehringer‐Ingelheim, Bristol‐Meyers Squibb, Celgene, Celltrion, Eli‐Lilly, Genzyme, LEO Pharma, Menlo Therapeutics, Novartis, OM Pharma, Pfizer, Regeneron, Samsung, Sandoz and UCB; and LC has performed paid activities as an advisor or speaker for AbbVie, Celgene, Janssen, LEO Pharma, Lilly, Novartis, Regeneron and Sanofi. The other authors have no conflicts of interest to declare.
References
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