key: cord-0737336-mv33a64r
authors: Beck, Lisa A.; Deleuran, Mette; Bissonnette, Robert; de Bruin-Weller, Marjolein; Galus, Ryszard; Nakahara, Takeshi; Seo, Seong Jun; Khokhar, Faisal A.; Vakil, Jignesh; Xiao, Jing; Marco, Ainara Rodriguez; Levit, Noah A.; O’Malley, John T.; Shabbir, Arsalan
title: Dupilumab Provides Acceptable Safety and Sustained Efficacy for up to 4 Years in an Open-Label Study of Adults with Moderate-to-Severe Atopic Dermatitis
date: 2022-05-03
journal: Am J Clin Dermatol
DOI: 10.1007/s40257-022-00685-0
sha: 3ff4fea7bdb6ab4f1b04d39446ed0b730c78a94d
doc_id: 737336
cord_uid: mv33a64r

BACKGROUND: Moderate‐to‐severe atopic dermatitis (AD) often requires long-term management with systemic therapies. OBJECTIVE: Our objective was to report the safety and efficacy of dupilumab treatment up to 4 years in adults with moderate-to-severe AD and efficacy in a subgroup of patients who transitioned from dupilumab once-weekly (qw) to administration every other week (q2w). METHODS: This interim analysis of the open-label extension study (NCT01949311) evaluated dupilumab 300 mg qw or q2w in adults previously enrolled in dupilumab trials for moderate-to-severe AD. Patients switched from qw to q2w following protocol amendment. The primary outcome was safety; efficacy was also assessed. RESULTS: Of 2677 patients enrolled and treated, 352 (13.1%) completed week 204 (end of efficacy assessments) and 202 (7.5%) completed safety follow-up through week 244. Self-reported compliance was 98.1%. Dupilumab’s safety profile was consistent with previous reports. Common treatment-emergent adverse events (≥5%) included nasopharyngitis, AD, upper respiratory tract infection, oral herpes, conjunctivitis, injection-site reaction, and headache. At week 204, mean ± standard deviation (SD) Eczema Area and Severity Index was 2.46 ± 3.98, and mean percent change from parent study baseline (PSBL) was −91.07%; mean ± SD Pruritus Numerical Rating Scale score was 2.10 ± 1.83, and mean percent change from PSBL was −68.74%. Efficacy was maintained in patients (n = 226) who transitioned from qw to q2w dosing. Limitations of this study included its open-label design, the lack of control arm, and smaller subsets of patients at later timepoints and receiving the approved q2w regimen. CONCLUSION: These results support dupilumab as continuous long-term treatment for adults with moderate-to-severe AD; efficacy was sustained following transition from qw to q2w dosing. TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT01949311. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40257-022-00685-0.

Atopic dermatitis (AD) is a common chronic inflammatory systemic disease characterized by intense itching and recurrent eczematous lesions [1] . Management of moderate-tosevere AD often requires long-term treatment with systemic therapies; however, many available AD treatments are not recommended for long-term use because of safety concerns, and some newer investigational treatments lack long-term safety data [2] . For example, systemic corticosteroids (SCSs) are often used to treat severe AD exacerbations but are not recommended for treatment durations longer than 2 weeks; rebound flares are common following treatment cessation [2, 3] . The maximum recommended treatment duration for cyclosporine is 1 year in the USA and 2 years in Europe because of safety concerns; cyclosporine also requires close monitoring of vital signs and laboratory parameters to detect untoward changes in blood pressure and renal function during use [2, 4] . Other systemic immunosuppressants, including methotrexate, azathioprine, and mycophenolate mofetil, are commonly used off label to treat moderate-to-severe AD, but serious adverse events (AEs) have been reported [2] . An open-label study assessed the efficacy and safety of methotrexate and azathioprine in patients with moderate-to-severe AD up to 5 years, but the study sample size was small (N = 27), and drug continuation at 5 years was low because of AEs and lack of efficacy [5] .

Dupilumab, a fully human VelocImmune ® -derived [6, 7] monoclonal antibody that blocks the shared receptor subunit for interleukin (IL)-4 and IL-13, is approved for patients with type 2 inflammatory diseases, including AD, asthma, and chronic rhinosinusitis with nasal polyps [8, 9] . In multiple phase III clinical trials of dupilumab monotherapy or in combination with topical corticosteroids (TCSs), dupilumab provided rapid and sustained improvements in AD signs and symptoms and quality of life, with an acceptable safety profile [10] [11] [12] [13] [14] [15] .

Given that AD is a chronic relapsing disease characterized by flares and often requires continuous long-term treatment for stable disease control, analyses of long-term safety and efficacy data over time are critically important. Previous analyses of dupilumab treatment in a placebo-controlled study up to 52 weeks (LIBERTY AD CHRONOS) and an open-label extension study up to 3 years (LIBERTY AD OLE) have demonstrated acceptable safety and sustained efficacy in adults with moderate-to-severe AD [10, 16, 17] . Our objective in this report is twofold: (1) to describe an interim analysis of safety and efficacy results from the LIB-ERTY AD OLE study in adults with moderate-to-severe AD treated with dupilumab up to 4 years and (2) to describe efficacy results in a subgroup of patients (n = 226) who transitioned from dupilumab 300 mg weekly (qw) after at least 156 weeks of treatment to 300 mg every 2 weeks (q2w) and were followed for approximately 48 weeks (median 48.5 weeks; interquartile range 45.71-51.71) after the transition.

The LIBERTY AD open-label extension (OLE) study (NCT01949311) is an ongoing phase III multicenter trial to assess the long-term safety and efficacy of dupilumab in adults with moderate-to-severe AD [18] . Two analyses (with data cutoff dates of April 11, 2016 , and December 1, 2018) have been previously reported [16, 17] . Here, we report results with a cutoff date of March 19, 2021 (database lock April 28, 2021), which includes patients from approximately 550 sites in 28 countries in North America, Europe, and Asia-Pacific (Table S1 in the electronic supplementary  material [ESM] ).

The OLE enrolled adult patients who previously participated in dupilumab AD trials (phases I-III) [10, 12, [18] [19] [20] [21] [22] [23] [24] [25] [26] . Patients were ineligible if they had an AE related to dupilumab that led to treatment discontinuation or a serious AE related to dupilumab in the parent study. Details of enrollment criteria have been reported in greater detail previously [17] .

Patients enrolled from the start of the study in October 2013 received a subcutaneous dose of dupilumab 200 mg qw (with a 400-mg loading dose). On June 12, 2014, the protocol was amended to a dose regimen of 300 mg qw based on results from a dose ranging study (NCT01859988). On November 12, 2019, the protocol was amended to a dose regimen of 300 mg q2w to align with the regimen approved by regulatory agencies [8, 9] . A complete list of protocol amendments is provided in Table 1 .

Concomitant treatments for AD, including TCSs and topical calcineurin inhibitors (TCIs), were permitted, although use of SCSs and nonsteroidal systemic immunosuppressive medications (including phototherapy) as rescue medications required temporary discontinuation from the study treatment for the duration of rescue treatment and for five half-lives of the rescue treatment. Following Protocol Amendment 7 (June 2, 2017), patients were not required to temporarily discontinue study treatment following rescue treatment with SCSs. Originally, the planned study duration per patient was up to 3 years of dupilumab treatment or until regulatory approval of dupilumab in the patient's enrollment country, whichever came first. The study duration was later amended to 5 years in Protocol Amendment 8 (January 8, 2018), allowing some patients to re-enter the study and resume dupilumab treatment at week 156 following a treatment interruption. Protocol amendment history has been reported in greater detail previously [17] .

This study was conducted in accordance with the Declaration of Helsinki, the International Council for Harmonisation guideline, good clinical practice, and local applicable regulatory requirements, including institutional review board approval. All patients provided written informed consent before any study procedures began.

The primary endpoint of the OLE was the incidence and rate (events per patient-year [PY]) of treatment-emergent AEs (TEAEs). Key secondary endpoints included the incidence and rate of serious TEAEs and AEs of special interest, proportion of patients with an Investigator's Global Assessment (IGA) score of 0 or 1 (clear or almost clear), and proportion of patients with a ≥75% improvement (reduction) in the Eczema Area and Severity Index (EASI) from baseline of the parent study (EASI-75). Of note, IGA and EASI assessments at the end of treatment visit were removed from the protocol and subsequently restored during amendments 6 and 7, respectively. Additional secondary endpoints included change and percent change in EASI from baseline, proportion of patients with a ≥50% or ≥90% reduction in EASI (EASI-50 or EASI-90) from baseline of parent study, change and percent change in weekly average Pruritus Numerical Rating Scale (NRS) score, proportion of patients with a ≥3-point improvement (reduction) from baseline in weekly average Pruritus NRS score or with a score of 0, proportion of patients with a ≥4-point reduction from baseline in weekly average Pruritus NRS or a score of 0, and percentage of patients requiring rescue treatment. Post hoc outcomes included the proportion of patients with a ≥2-point improvement in IGA score from baseline. Additional post hoc outcomes assessed dupilumab efficacy before and after patients switched from qw to q2w dosing, including the proportion of patients with IGA 0 or 1, mean EASI, and mean weekly average Pruritus NRS score at baseline of q2w dosing and 48 weeks prior to and after this baseline. The proportion of patients who switched qw to q2w dosing with EASI ≤7 or Pruritus NRS score ≤4 who maintained a continuous wellcontrolled response for >24 weeks was also assessed.

Analyses were performed on the safety analysis set, which comprised patients who received at least one dose of the study drug. Rescue medication use was manually adjudicated. Exposure-adjusted analyses for safety outcomes were calculated for the duration of study participation. Efficacy outcomes were assessed up to week 204 and included all observed data at each timepoint; missing values were not imputed. Efficacy data were only reported up to week 204 because of the small number of patients with efficacy data collected after this timepoint. Sensitivity analyses on patients who completed week 204 (or who withdrew but were enrolled in the study at least 204 weeks prior to the OLE study cutoff) were performed on some EASI and weekly average Pruritus NRS endpoints, using observed cohort and the last observation carried forward (LOCF; missing values imputed) approach. SAS software, version 9.4 (SAS Institute Inc., Cary, NC, USA), was used for all analyses. Because of the absence of a control arm in LIBERTY AD OLE, safety results from LIBERTY AD CHRONOS (NCT02260986) [10] are provided for comparison. The CHRONOS trial was selected for comparison because of its large sample size, 52-week duration, and mandatory use of concomitant TCSs.

A total of 2827 adult patients were screened from 14 parent studies (Fig. 1 ). Screen failures (n = 149) included the following: consent withdrawn (n = 8), exclusion criteria met (n = 62), inclusion criteria not met (n = 48), lost to follow-up (n = 2), and other (n = 29). Of these, 2678 were enrolled and 2677 were included in the safety analysis set (one patient was enrolled but not treated [17] ; no new patients were enrolled since the previous report. During the OLE treatment period, 53.3% of patients used TCSs, 16.3% used TCIs, 56% used TCSs or TCIs, and 13.6% used TCSs and TCIs. Few patients required rescue medication (47 [1.8%]); of these patients, 44 (1.6%) used systemic corticosteroids, and three (0.1%) used cyclosporine. The extent of either TCS, TCI, or both classes for rescue medication was not captured as part of the protocol. Table 3 shows the mean duration of dupilumab exposure (300 mg qw or dupilumab 300 mg q2w) among patients who switched from qw to q2w. The overall duration of exposure to open-label dupilumab among this group of patients ranged from 182 to ≥260 weeks; mean ± standard deviation (SD)/ median exposure: 241.7 ± 16.4/242.1 weeks. This cohort (n = 226) had an initial exposure duration of at least 3 years to dupilumab 300 mg qw. The duration of time patients spent on the qw dose ranged from 156 to <260 weeks, and the duration of time patients spent on the q2w dose regimen ranged from 4 to <76 weeks; mean ± SD/median qw exposure 195.0 ± 19.2/194.1 weeks; mean ± SD/median q2w exposure 46.7 ± 7.4/48.5 weeks. Of those who received the q2w regimen, 175 patients had exposure for 24 to <52 weeks, and 47 had exposure for >52 weeks.

A total of 14,569 TEAEs were reported during the OLE, with 2273 (84.9%) patients experiencing at least one TEAE ( Table 4 ). The exposure-adjusted TEAE incidence rate was 256.86 number of events [nE]/100 PY. Most TEAEs were mild to moderate in severity, with 10.4 and 9.8% of patients experiencing at least one serious or severe TEAE, respectively. Treatment was discontinued because of TEAEs in 3.7% of patients. Serious TEAEs deemed related to study treatment occurred in 1.2% of patients, with each TEAE reported by Medical Dictionary for Regulatory Activities (MedDRA) preferred term (PT) occurring in <0.1% of patients. Three deaths occurred during the OLE, all of which were deemed unrelated to study treatment. Circumstances of death were natural causes in an 88-year-old woman, unknown causes in a 60-year-old woman approximately 5 months after the final dose of study drug, and unknown causes in a 42-year-old man. The most common TEAEs (≥5% incidence; reported by PT) included nasopharyngitis, AD, upper respiratory tract infection, oral herpes, conjunctivitis, injection-site reaction, and headache. Incidences of the MedDRA high-level terms (HLTs) injection-site reactions and herpes viral infections were 9.8 and 12.8%, of patients. The exposure-adjusted incidence rates for these TEAEs in the OLE at week 204 were generally lower than in the 300 mg qw arm in CHRONOS at 52 weeks (Table 4 ) [17] .

Rates of serious TEAEs and serious TEAEs related to treatment were similar between patients in the OLE and Table 2 Study completion, reasons for withdrawal, and treatment history Data are expressed as n (%) unless otherwise specified AD atopic dermatitis, AE adverse event, OLE open-label extension, q2w every 2 weeks, qw weekly, TCI topical calcineurin inhibitor, TCS topical corticosteroid a These patients completed the treatment and end-of-study periods b Includes reasons of relocation, desire for pregnancy, did not want to discontinue treatment for 12 weeks during the follow-up period, work/ school conflict, and personal reasons not specified. Further details for patient withdrawal because of personal reasons were not captured c Includes both those on treatment at the time of withdrawal and those not on treatment during the safety follow-up period. Further details on the AE are not provided as with a formally reported clinical safety event d Includes decisions because of alcohol abuse, AD worsening during follow-up period (n = 2), multiple complex medical issues that outweighed study benefits, principal investigator decision, positive result of hepatitis B core antibody test, resignation of the investigator, site closing, patient could not commit to scheduled study visits (n = 2), patient's declining health, and medical monitor decision to discontinue because of a serious AE (no further details provided by the investigator) causing the patient to discontinue dupilumab for 6 months Conjunctivitis (reported as a narrow cluster of MeDRA PTs: conjunctivitis, conjunctivitis allergic, conjunctivitis bacterial, conjunctivitis viral, and atopic keratoconjunctivitis) was reported in 20% of patients, with most cases being of mild (9.3%) or moderate (9.8%) severity as assessed by the investigator (Table 4 ). One case of serious conjunctivitis was reported but was deemed unrelated to the study drug. The exposure-adjusted incidence rate of conjunctivitis in the OLE (15.66 nE/100 PY) was lower than in the 300 mg qw arm at 52 weeks in CHRONOS (30.6 nE/100 PY). Most cases of conjunctivitis resolved during the study treatment period (775 of 888 cases; 87%). The most frequently used ophthalmic treatments included intraocular corticosteroids, antiallergy medications, and anti-infectives. Severe conjunctivitis occurred in 26 (1.0%) patients, and conjunctivitis leading to drug discontinuation occurred in 14 (0.5%) patients. Most conjunctivitis incidents occurred early in the study, and incidence decreased throughout the course of treatment (Table 4 ).

AD signs and symptoms improved throughout the OLE, with EASI and weekly average Pruritus NRS scores improving rapidly during the first several weeks, followed by incremental improvements throughout the remainder of the treatment period (Table 5 , Figs. 2, 3, 4) . A slight transient increase in mean EASI and mean weekly average Pruritus NRS score was observed at week 156 (visit 31), corresponding with patient re-entry to the study following treatment interruption (Figs. 3 and 4) . Sensitivity analyses conducted to assess any bias on treatment outcomes because of patient withdrawal were consistent with results from all observed patients (Table 5 , Figs. 3, 4) .

By week 204, a total of 64.4% of patients achieved an IGA 0 or 1, 80.8% achieved a reduction in IGA of ≥2 points from the parent study baseline, and 94.9, 90.9, and 75.8% achieved EASI-50, EASI-75, and EASI-90, respectively (Table 5 ). Mean EASI improved from week 52 (3.15) to week 204 (2.46), as did mean weekly average Pruritus NRS scores (2.37 at week 52 to 2.10 at week 204). The proportion of patients achieving a ≥3-point improvement in weekly average Pruritus NRS score from parent study baseline at week 204 (78.7%) was similar to that at week 52 (78.2%), whereas the proportion of patients achieving a ≥4-point improvement in weekly average Pruritus NRS score from parent study baseline was greater at week 204 (70.8%) than at week 52 (66.9%).

Relative to q2w dosing baseline and 48 weeks prior to dose transition, measures of AD signs and symptoms were stable 48 weeks post-switch among patients who transitioned from qw to q2w dosing (N = 226; Table 5 , Fig. 5 ).

The mean EASI at q2w dosing baseline (1.92) was similar to that 48 weeks after the switch (1.93; Table 5 , Fig. 5) . A similar trend was observed for weekly average Pruritus NRS score (q2w dosing baseline mean score = 2.15, score who transitioned from qw to q2w had an NRS score ≤4 (low burden of itch) or EASI ≤7 (mild) at the time of the switch, and more than 80% maintained this stringent response on q2w for 6 months continuously (Fig. 6) , indicating well-controlled disease without any exacerbation related to the changed dosing frequency to the approved posology. Week 52 (n = 2207)

Week 100 (n = 1065)

Week 148 (n = 557)

Week 

In this study, dupilumab showed an acceptable safety profile and sustained efficacy in adults with moderate-tosevere AD for up to 4 years. Safety data reported here are consistent with data from previous controlled studies of dupilumab up to 52 weeks [10, 12, 19] , and common AEs (nasopharyngitis, AD, upper respiratory tract infection, conjunctivitis, headache, oral herpes, and injection-site reactions) are consistent with the known safety profile of dupilumab. These AEs are also similar to those reported in a recent analysis of real-world dupilumab safety data, in which conjunctivitis, blepharitis, keratitis, herpes simplex, and headache were the most commonly reported AEs [27] .

Exposure-adjusted incidence rates of TEAEs declined over time, with lower rates in this 4-year analysis (256.86 nE/100 PY) compared with the 3-year analysis of this trial (270.1 nE/100 PY) and an earlier 52-week controlled trial (504.5 nE/100 PY) [10, 17] . Treatment discontinuation because of AEs or lack of efficacy was low (4.3 and 2.2% incidence, respectively), and few patients required rescue treatment (1.8% incidence), indicating well-controlled disease. Compliance with study treatment was high (98.1%).

Clinical trials of dupilumab for the treatment of AD report a greater incidence of ocular surface disease, including conjunctivitis, among patients receiving dupilumab compared with placebo [28, 29] . In this analysis, the exposure-adjusted incidence rate of conjunctivitis was 15.66 nE/PY, which was lower than that reported at 52 weeks in a placebo-controlled Kaplan-Meier curve of continuous maintenance of NRS score ≤4 or EASI ≤7 following dupilumab dose switch from 300 mg weekly to 300 mg q2w. Patients maintained response (treated >24 weeks or not) as censored at last assessment within 24 weeks of dose switch. EASI Eczema Area and Severity Index, NRS Numerical Rating Scale, q2w every 2 weeks trial (30.6 nE/100 PY) and comparable with that reported in the 3-year analysis of this trial (16.14 nE/100 PY) [10, 17] . Most cases of conjunctivitis were mild or moderate in severity, and treatment discontinuation because of conjunctivitis was rare (0.5% of patients). Conjunctivitis incidence also decreased throughout the course of treatment in this study, with the majority of cases (61%) occurring during the first year of dupilumab treatment, and most conjunctivitis events recovered/resolved during the treatment period. These data show that the exposure-adjusted incidence rate of conjunctivitis declined over time. Similar to conjunctivitis, the incidence of injection-site reactions also decreased over time, with a lower incidence in this 4-year analysis (15.11 nE/100 PY) than in the 3-year analysis (16.70 nE/100 PY) and the 52-week controlled trial (78.02 nE/100 PY) [10, 17] . The same was true for skin infections, which decreased from 9.75 nE/100 PY in the 52-week trial to 5.69 nE/100 PY in the 3-year analysis and 5.57 nE/100 PY in the 4-year analysis. These improvements may possibly be due to more efficient control of AD with continued dupilumab treatment.

In this study, dupilumab demonstrated rapid improvements in AD signs and symptoms in the first several weeks of treatment, following by sustained efficacy up to 204 weeks. Sensitivity analyses of EASI and weekly average Pruritus NRS score were consistent with results from analyses on all observed patients, suggesting that patient withdrawal did not bias the results.

To align the OLE study dose regimen with the dose regimen approved by regulatory agencies, patients transitioned from dupilumab 300 mg qw to q2w following Protocol Amendment 9. This subgroup of patients represents the longest treated cohort of patients in the OLE, with a mean total duration of dupilumab exposure of over 4.5 years. Previous controlled studies of dupilumab have demonstrated no differences in safety or efficacy between qw and q2w dose regimens, suggesting that dupilumab 300 mg q2w would achieve results similar to those with 300 mg qw [10, 12, 19] . Indeed, in this study, dupilumab showed sustained efficacy following dose regimen transition from 300 mg qw to 300 mg q2w, with stable signs and symptoms 48 weeks post-transition. Continuous maintenance of disease control, defined as EASI ≤7 or NRS score ≤4 for 24 weeks without exacerbation, was observed in more than 80% of patients who achieved this response at the time of dosage switch.

Strengths of this study include the duration of treatment and overall sample size. Limitations include the open-label design, the absence of a placebo arm, treatment interruptions because of protocol amendments, the smaller subset of patients who received q2w dosing, the smaller subset of patients who transitioned from qw to q2w dosing, and the smaller sample size at later timepoints, which was primarily because of study termination by the sponsor following regulatory approval of dupilumab in the enrollment country. Furthermore, the 300 mg qw dosing regimen is not an approved regimen. Finally, all data reported here correspond to the overall patient population rather than the continuously treated population, which had a smaller sample size at later timepoints.

Safety and efficacy results of dupilumab treatment up to 4 years supported dupilumab as a continuous long-term treatment for adults with moderate-to-severe AD. Furthermore, dupilumab efficacy was sustained following dose regimen transition from 300 mg qw to 300 mg q2w.

The online version contains supplementary material available at https:// doi. org/ 10. 1007/ s40257-022-00685-0.

principal investigator for Boehringer Ingelheim, Dermira, Galderma, Glenmark, Incyte, LEO Pharma, Pfizer, Regeneron Pharmaceuticals, Inc., and Sanofi. Takeshi Nakahara has received speaker fees from Maruho and Sanofi. Seong Jun Seo has acted as speaker, investigator, and consultant for AbbVie, Eli Lilly, LEO Pharma, Sanofi. Faisal Khokhar, Jing Xiao, Noah Levit, and Arsalan Shabbir are employees and shareholders or Regeneron Pharmaceuticals, Inc. Jignesh Vakil, Ainara Rodriguez Marco, John O'Malley are employees of and may hold stock and/or stock options in Sanofi.

Ethics approval This study was conducted in accordance with the ethical standards of the responsible committees and the Declaration of Helsinki and with the International Council for Harmonisation guidelines for good clinical practice. The trial was overseen by an independent data and safety monitoring board. The protocol was reviewed and approved by institutional review boards/ethics committees at all centers.

Consent to participate Written informed consent was obtained from all patients or their proxies.

Availability of data and material Qualified researchers may request access to study documents (including the clinical study report, study protocol with any amendments, blank case report form, and statistical analysis plan) that support the methods and findings reported in this manuscript. Individual anonymized participant data will be considered for sharing once the product and indication has been approved by major health authorities (e.g., US FDA, European Medicines Agency, Pharmaceuticals and Medical Devices Agency), if there is legal authority to share the data and there is not a reasonable likelihood of participant re-identification. Submit requests to https:// vivli. org/.

Code availability Not applicable.

Author contributions LAB, MD, RB, MdeBW, RG, TN, and SJS acquired data. JX conducted the statistical analyses on the data. All authors interpreted the data, provided critical feedback on the manuscript, approved the final manuscript for submission, and are accountable for the accuracy and integrity of the manuscript.

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Lisa A. Beck 1 · Mette Deleuran 2 · Robert Bissonnette 3 · Marjolein de Bruin-Weller 4 · Ryszard Galus 5 · Takeshi Nakahara 6 · Seong Jun Seo 7 · Faisal A. Khokhar 8 · Jignesh Vakil 9 · Jing Xiao 8 · Ainara Rodriguez Marco 10 · Noah A. Levit 8 · John T. O'Malley 11 · Arsalan Shabbir 8