Dermatol Ther (Heidelb) (2022) 12:1481–1491 https://doi.org/10.1007/s13555-022-00734-w BRIEF REPORT Indirect Treatment Comparison of Baricitinib versus Dupilumab in Adults with Moderate-to-Severe Atopic Dermatitis Marjolein S. de Bruin-Weller . Esther Serra-Baldrich . Sebastien Barbarot . Susanne Grond . Christopher Schuster . Helmut Petto . Jean-Philippe Capron . Afaf Raibouaa . Thomas Werfel Received: March 1, 2022 / Published online: May 11, 2022  The Author(s) 2022 ABSTRACT therapies (population A) and cyclosporine (population B). Population A was additionally Introduction: Indirect treatment comparison examined as monotherapy. was used to compare approved doses of barici- Results: For the Eczema Area and Severity tinib and dupilumab for treating adult patients Index (EASI) 75, baricitinib and dupilumab were with moderate-to-severe atopic dermatitis (AD) similar. A C 4-point improvement in itch who are candidates for systemic therapy. numerical rating scale (NRS) was significantly Methods: Baricitinib and dupilumab were more likely with baricitinib 4 mg than dupilu- compared (Bucher method) at weeks 4 and 16. mab in population A as monotherapy (RR = Performance in combination with topical cor- 2.62, 95% CI 1.22, 5.61, p = 0.013) and in TCS ticosteroids (TCS) was analyzed in patients with combination at week 4. These differences were inadequate response or inadvisable to topical not significant by week 16. For the Dermatology Life Quality Index (DLQI), baricitinib 4 mg and dupilumab were similar on mean difference in M. S. de Bruin-Weller (&) change from baseline (MDcfb), though some Department of Dermatology and Allergology, differences were seen between baricitinib 2 mg University Medical Center, Utrecht, The and dupilumab at week 16 for the population A Netherlands monotherapy (MDcfb = 2.05, 95% CI 0.53, e-mail: m.s.debruin-weller@umcutrecht.nl 3.56, p = 0.016) and TCS combination therapy E. Serra-Baldrich (MDcfb = 2.48, 95% CI 0.46, 4.50, p = 0.016) Department of Dermatology, Cutaneous Allergy groups, and in population B (MDcfb = 3.38 95% Unit, Hospital Sant Pau, Universitat Autònoma Barcelona, Barcelona, Spain CI 1.18, 5.58, p = 0.003). Conclusions: Baricitinib potentially offers more S. Barbarot rapid improvement in itch while providing Department of Dermatology, Nantes Université, similar efficacy on EASI75 and DLQI outcomes CHU Nantes, INRAE, UMR 1280 PhAN, 44000 Nantes, France compared with dupilumab. S. Grond  C. Schuster  H. Petto  J.-P. Capron  Keywords: Atopic dermatitis; Indirect A. Raibouaa Eli Lilly and Company, Indianapolis, IN, USA treatment comparison; Systemic therapies T. Werfel Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany 1482 Dermatol Ther (Heidelb) (2022) 12:1481–1491 To support physicians when choosing appro- Key Summary Points priate treatments for AD, we conducted an ITC across all approved systemic therapies for the Head-to-head (H2H) trial evidence treatment of moderate-to-severe AD in adults regarding the performance of novel with PBO-controlled randomized controlled therapies versus their competitors is often trial evidence. lacking. Indirect treatment comparisons (ITC) METHODS allow the results of existing trials to be compared in a rigorous way and can help To identify relevant studies for our ITC, we to bridge knowledge gaps when H2H systematically reviewed the literature for pla- comparisons are not available. cebo-controlled trials evaluating systemic ther- apies in adults with moderate-to-severe AD over Baricitinib represents an approved oral four waves starting in 2018 with updates in treatment option for adult patients with 2019, and May and December 2020. Eligibility moderate-to-severe AD that offers similar criteria for the review were: studies in adults efficacy on the Eczema Area and Severity with confirmed moderate-to-severe AD; ran- Index (EASI)75 and Dermatology Life domized controlled trials of a comparative Quality Index (DLQI) to dupilumab when investigation (one of which could be PBO); and indirectly compared. studies published in English or German. We Baricitinib potentially offers more rapid interrogated MEDLINE and Embase, both via improvement in itch, a key symptom for Ovid Search Platform, and The Cochrane Cen- patients, than dupilumab when indirectly tral Register of Controlled Trials (CENTRAL) for compared. published studies as well as ClinicalTrials.gov (http://clinicaltrials.gov/), the International Clinical Trials Registry Platform Search Portal, and the search portal of the World Health Organization to identify potentially relevant studies based on ongoing trials. INTRODUCTION The only approved treatments with PBO- controlled trial data identified by the review at Baricitinib, a selective Janus kinase (JAK)1/JAK2 this time were dupilumab [6] and baricitinib. inhibitor, is approved in several countries for The approved dose of dupilumab (300 mg sub- the treatment of moderate-to-severe atopic cutaneously every 2 weeks following a loading dermatitis (AD) in adults who are candidates for dose of 600 mg) [7, 8] was then indirectly systemic therapy [1]. It has proven effective compared with baricitinib 2/4 mg once daily [1] both as monotherapy and in combination with using PBO as the common comparator (Fig. 1). topical corticosteroids (TCS) [2, 3]. When treatment data were available from more At present, there are no existing head-to- than one study versus PBO, standard meta- head (H2H) trials comparing the efficacy of analysis methods were applied before conduct- baricitinib with other approved systemic thera- ing ITC by means of the Bucher methodology pies available for the management of AD in this ITC [5]. patient population. In such circumstances, Patient-level data were available for all methodological tools such as indirect treatment baricitinib studies, whereas for dupilumab out- comparisons (ITC) are often employed by comes, data were extracted from the published researchers [4, 5]. ITC methodologies use the literature. The ITC was conducted in two results of direct comparisons with a common patient populations with subcohorts: popula- comparator, such as placebo (PBO), to evaluate tion A and population B. Population A consisted the relative efficacy of different interventions. Dermatol Ther (Heidelb) (2022) 12:1481–1491 1483 Fig. 1 Structure of ITC analysis of BARI 2/4 mg versus were intolerant of, had contraindications to, or did not DUPI 300 mg Q2W. BARI baricitinib, DUPI dupilumab, respond to topical treatments. Population B: patients who ITC indirect treatment comparison, QxW every x weeks, were also intolerant of, had contraindications to, or did TCS topical corticosteroids. Population A: patients who not respond to, cyclosporine of two cohorts, while population B included versus PBO for each of the binary outcomes. only one cohort: Where RRs were [ 1, results favored baricitinib, Population A: patients who were intolerant while RRs \ 1 favored dupilumab. For Derma- of, had contraindications to, or did not respond tology Life Quality Index (DLQI) assessments, to topical treatments the ITC was based on mean difference in change from baseline (MDcfb). MDcfb [ 0 favored • Cohort 1: patients receiving baricitinib or dupilumab while MDcfb \ 0 favored baricitinib. dupilumab as monotherapy An overview of the population groups is pro- • Cohort 2: patients receiving baricitinib or vided in Table 1. dupilumab in combination with TCS Informed by the primary and key secondary Population B: patients who were also intol- endpoints common across the trials identified erant of, had contraindications to, or did not in the systematic literature review, we assessed respond to cyclosporine: the following efficacy outcomes in our study at week 4 and again at week 16: the proportion of • Cohort 1: patients receiving baricitinib or patients with C 75% improvement in Eczema dupilumab in combination with TCS Area and Severity Index (EASI75), the propor- The ITC was based on the relative efficacy tion of patients with C 4-point improvement in (relative risk [RR]) of the two agents assessed itch Numeric Rating Scale (NRS) from baseline 1484 Dermatol Ther (Heidelb) (2022) 12:1481–1491 Table 1 Relevant trials identified by systematic literature review Patient population of adults with moderate-to-severe AD BARI randomized DUPI randomized clinical trials clinical trials Population A: Monotherapy: Monotherapy: patients who had failed topical treatment, or had contraindication to or BREEZE-AD1 [3] SOLO-1 [21] were intolerant of topical treatments BREEZE-AD2 [3] SOLO-2 [10] Phase 2b [22] TCS combination TCS combination therapy: therapy: BREEZE-AD7 [4] CHRONOS [23] Population B: TCS combination TCS combination patients who had inadequate response to existing topical medications and therapy: therapy: failed cyclosporine, or had contraindications to or were intolerant to BREEZE-AD4 CAFÉ [25] cyclosporine (NCT03428100) [24] While we deemed a phase II trial of dupilumab to meet the inclusion criteria, a phase II trial of baricitinib had too small a sample size for inclusion AD atopic dermatitis, BARI baricitinib, DLQI Dermatology Life Quality Index, DUPI dupilumab, TCS topical corticosteroid (peak daily pruritus NRS score used as equiva- RESULTS lent; both instruments measure worst level of itch within the past 24 h [9–11]), and change At the time of the systematic literature review from baseline (CFB) in Dermatology Life Qual- (SLR), nine parallel PBO trials (four baricitinib ity Index (DLQI). and five dupilumab) covering 3364 patients Missing data were accounted for by non-re- were identified to inform the ITC (Table 1). sponder imputation (NRI) for binary outcomes, Baseline characteristics for each of the trials are while for the DLQI, least-squared means were given in Table 2 and are consistent with com- selected from the relevant included studies. parable disease severity based on EASI, itch, and Patients in receipt of rescue treatment or who DLQI scores across all included studies. The discontinued treatment were considered non- results of the ITC analysis are summarized in responders. Statistical analyses were conducted Table 3. In population A at week 4, there was no using the CHEETAH tool (Indirect Comparison significant difference between EASI75 response on results from 2 Meta-Analyses version 1.1), a rates for either treatment group, though RR program developed by Eli Lilly based on the R values numerically favored both baricitinib 2 package ‘‘meta’’ [12]. and 4 mg. Similarly, at week 16 there was no statistically significant difference, though in Compliance with Ethics Guidelines this instance, RR values numerically favored dupilumab. This pattern was replicated in pop- This article is based on previously conducted ulation B. studies and does not contain any new studies With respect to C 4-point improvement in with human participants or animals performed itch NRS from baseline between baricitinib 2 or by any of the authors. 4 mg and dupilumab in either monotherapy or TCS combination therapy studies at week 16, no Dermatol Ther (Heidelb) (2022) 12:1481–1491 1485 Table 2 Baseline characteristics of patients in monotherapy studies included in the ITC Study Molecule Baseline Age (years; mean) Mean baseline scores (SD) (therapy) population [SD] EASI DLQI Itch/ pooled dataa,b pruritisd NRS (n) BREEZE-AD1 BARI (Mono) 497 35.5 (13.3) 31.8 13.8 6.6 (2.1) (12.8) (7.3) BREEZE-AD2 BARI (Mono) 490 35.0 (13.3) 33.5 14.5 6.7 (2.2) (13.8) (8.0) BREEZE-AD7 BARI (Combi) 329 33.8 (12.5) 29.7 15.0 7.1 (1.9) (12.3) (7.8) BREEZE-AD4 BARI (Combi) 370 38.0 (13.8) 31.5 13.9 6.8 (2.0) (12.5) (7.5) SOLO 1 DUPI (Mono) 448 38.5c 31.1c 13.5c 7.7c SOLO 2 DUPI (Mono) 469 34.5c 29.6 15.0 7.8 (N/A) (N/A) Phase 2b trial DUPI (Mono) 125 38.3 (12.6) 33.4 13.7 6.3 (1.8)e/6.5 (14.2) (6.7) (2.0) CHRONOS DUPI (Combi) 421 35.6 (N/A) 29.9 13.9c 7.6c (N/A) CAFÉ DUPI (Combi) 215 38.2 (13.1) 33.1 13.5c 6.5 (2.3) (10.1) N/A not applicable a Pooled data for approved dosage regimens and placebo b In BREEZE-AD1, patients were randomized to receive baricitinib 2 mg (n = 123), baricitinib 4 mg (n = 125), baricitinib 1 mg (n = 127; not included in pooled data), or placebo (n = 249); in BREEZE-AD2, patients were randomized to receive baricitinib 2 mg (n = 123), baricitinib 4 mg (n = 123), baricitinib 1 mg (n = 125; not included in pooled data), or placebo (n = 244). In BREEZE-AD4, all patients received TCS and were randomized to baricitinib 2 mg (n = 185), baricitinib 4 mg (n = 92), baricitinib 1 mg (n = 93; not included in pooled data), or placebo (n = 93); in BREEZE-AD7, all patients received TCS and were randomized to baricitinib 2 mg (n = 109), baricitinib 4 mg (n = 111), or placebo (n = 109). In SOLO 1, patients were randomized to receive dupilumab 300 mg Q2W (n = 224), dupilumab 300 mg Q1W (n = 223; not included in pooled data), or placebo (n = 224); in SOLO 2, patients were randomized to receive dupilumab 300 mg Q2W (n = 233), dupilumab 300 mg Q1W (n = 239; not included in pooled data), or placebo (n = 236); in the phase 2b trial, patients were randomized to receive dupilumab 300 mg Q2W (n = 64), placebo (n = 61), or other regimens not included in pooled data: dupilumab 100 mg Q4W (n = 65), dupilumab 300 mg Q4W (n = 65), dupilumab 300 mg Q1W (n = 63), or dupilumab 200 mg Q2W (n = 61). In CHRONOS, all patients received TCS and were randomized to dupilumab 300 mg Q2W (n = 106), dupilumab 300 mg Q1W (n = 319; not included in pooled data), or placebo (n = 315); in CAFÉ, all patients received TCS and were randomized to dupilumab 300 mg Q2W (n = 107), dupilumab 300 mg Q1W (n = 110; not included in pooled data), or placebo (n = 108) c Weighted median values d For the baricitinib trials, Itch NRS is reported, and for the dupilumab studies, peak pruritus is reported. The phase 2b trial reported both itch and pruritus NRS e Placebo only 1486 Dermatol Ther (Heidelb) (2022) 12:1481–1491 Table 3 Results of the indirect treatment comparison of baricitinib and dupilumab in adult patients with moderate-to- severe atopic dermatitis (AD) Outcome Therapy BARI 2 mg versus DUPI BARI 4 mg versus DUPI (population) 300 mg Q2W 300 mg Q2W Relative risk (95% CI) EASI75 at Week 4 Monotherapy (pop. 1.32 (0.66, 2.63), p = 0.427 1.84 (0.96, 3.52), p = 0.064 A) TCS combo therapy 1.00 (0.49, 2.02), p = 0.990 1.45 (0.74, 2.85), p = 0.281 (pop. A) TCS combo therapy 1.35 (0.49, 3.69), p = 0.559 2.19 (0.80, 5.99), p = 0.128 (pop. B) EASI75 at week 16 Monotherapy (pop. 0.66 (0.41, 1.05), p = 0.081 0.82 (0.52, 1.30), p = 0.404 A) TCS combo therapy 0.62 (0.38, 1.02), p = 0.058 0.69 (0.43, 1.11) p = 0.129 (pop. A) TCS combo therapy 0.76 (0.42, 1.38), p = 0.365 0.87 (0.46, 1.63), p = 0.656 (pop. B) Itch NRS C 4 point Monotherapy (pop. 1.49 (0.66, 3.33), p = 0.337 2.62 (1.22,5.61), p = 0.013 improvement at week 4 A) TCS combo therapy 1.14 (0.69, 2.91), p = 0.345 2.16 (1.08, 4.31), p = 0.029 (pop. A) TCS combo therapy 1.76 (0.55, 5.66), p = 0.341 2.98 (0.93, 9.59), p = 0.066 (pop. B) Itch NRS C 4 point Monotherapy (pop. 0.65 (0.36, 1.17), p = 0.147 0.95 (0.55, 1.65), p = 0.866 improvement at week 16 A) TCS combo therapy 0.63 (0.37, 1.08), p = 0.096 0.73 (0.43, 1.23), p = 0.240 (pop. A) TCS combo therapy 0.87 (0.34, 2.22), p = 0.768 1.45 (0.56, 3.71), p = 0.442 (pop. B) Mean difference in change from baseline (95% CI) CFB DLQI at week 4 Monotherapy (pop. 1.79 (0.33, 3.25), p = 0.016 -0.11 (-1.34, 1.12) p = 0.86 A) TCS combo therapy 1.07 (-0.78, 2.92), -0.62 (-2.46, 1.22), p = 0.509 (pop. A) p = 0.256 TCS combo therapy 0.56 (-1.45, 2.57), -0.95 (-3.11, 1.21), p = 0.388 (pop. B) p = 0.585 Dermatol Ther (Heidelb) (2022) 12:1481–1491 1487 Table 3 continued Outcome Therapy BARI 2 mg versus DUPI BARI 4 mg versus DUPI (population) 300 mg Q2W 300 mg Q2W CFB DLQI at week 16 Monotherapy (pop. 2.05 (0.53, 3.56), p = 0.008 0.68 (-0.77, 2.14), p = 0.358 A) TCS combo therapy 2.48 (0.46, 4.50), p = 0.016 1.09 (-0.93, 3.11), p = 0.291 (pop. A) TCS combo therapy 3.38 (1.18, 5.58), p = 0.003 2.00 (-0.41, 4.41), p = 0.104 (pop. B) For EASI75 and Itch NRS C 4, relative risk \ 1 indicates a result favoring dupilumab. Relative risk [ 1 indicates a result favoring baricitinib. For DLQI, MDcfb [ 0 indicates a result favoring dupilumab and MDcfb \ 0 favors baricitinib. Results that attained statistical significance are given in bold text BARI baricitinib, DLQI Dermatology Life Quality Index, DUPI dupilumab, EASI Eczema Area and Severity Index, NRS Numeric Rating Scale, QxW every x weeks statistically significant differences were evident, clinically meaningful, where a meaningful although RR values numerically favored dupi- clinical difference has been determined to be 4 lumab except for baricitinib 4 mg in population [13]. B. At week 4, however, C 4-point itch NRS improvement was significantly more likely to be seen with baricitinib 4 mg than dupilumab in DISCUSSION population A for both monotherapy and TCS combination trials. In population B, there were This indirect comparison analysis found that no statistically significant differences between baricitinib and dupilumab might have similar baricitinib 2 or 4 mg compared with dupilumab efficacy across EASI75, C 4-point improvement in achieving C 4-point itch improvement at in itch NRS, and DLQI improvement (baricitinib week 16; RR values numerically favored dupi- 4 mg) after 16 weeks of treatment, confirming lumab for these comparisons apart from the the findings of a recently published network C 4-point itch improvement seen in baricitinib meta-analysis (NMA) and extending them to an 4 mg. earlier time point (week 4) [14]. For DLQI, no significant differences were For earlier time points, baricitinib 4 mg was observed in MDcfb between baricitinib 4 mg associated with a higher likelihood of an and dupilumab as monotherapy or TCS combi- improvement in itch relative to dupilumab. nation therapy in either population at week 4 or This finding is largely in keeping with the week 16. However, DLQI at week 4 significantly existing evidence on baricitinib and other JAK favored dupilumab over baricitinib 2 mg in the 1/2 inhibitors, where improvements in itch population A monotherapy group. At week 16, have been observed as early as one day after DLQI MDcfb significantly favored dupilumab treatment initiation [15, 16]. When asked, versus baricitinib 2 mg as both monotherapy in patients often rate itch as the symptom they population A and TCS combination therapy in find most bothersome and rate as their most population A. This difference was also seen in important treatment goal [17, 18]. The population B at week 16 in our analysis. While increased expression of pruritogens, including these differences were statistically significant, TSLP, IL-4, IL-13, and IL-31, is thought to be they did not meet the criteria for being most important for itch induction in AD [19, 20]. These pruritogens may signal via JAKs 1488 Dermatol Ther (Heidelb) (2022) 12:1481–1491 [21] and consequently be directly inhibited by improvement in itch, a key symptom for baricitinib. Such inhibition may explain barici- patients, while it might also provide similar tinib’s ability to rapidly reduce itch. By week 16, efficacy in terms of EASI75 and DLQI outcomes itch improvement was comparable to that compared with dupilumab based on indirect achieved by dupilumab. Our findings will serve evidence [24–28]. to support clinical decision-making with regards to treatment options, not only several months into patients’ therapy but also in the ACKNOWLEDGEMENTS early weeks after treatment initiation. H2H trial data, considered to be the highest form of evidence, can take time to emerge, Funding. The study and this analysis were perhaps delaying access to potentially beneficial funded by Eli Lilly and Company, as was the therapies for health systems and patients. In Rapid Service Fee associated with the publica- such circumstances, NMAs and ITCs like our tion of this manuscript. study can help to provide valuable evidence before H2H data are available. In this case, we Medical Writing and/or Editorial Assis- chose an ITC framework as only one other drug tance. Mr. Alan Ó Céilleachair, an employee of was identified by the SLR. Several factors should Eli Lilly and Company, provided scientific be considered when interpreting our results. writing and editorial support on the manu- Evidence identified by the systematic review script. Support for this assistance was funded by was more limited for the TCS combination Eli Lilly and Company. groups than for monotherapy. Also, it is possi- ble that differences in trial design, such as TCS Authorship. All named authors meet the use not being standardized across trials and International Committee of Medical Journal different washout periods, limit cross-trial Editors (ICMJE) criteria for authorship for this comparability in the AD research landscape. article, take responsibility for the integrity of Heterogeneity across trials designs and statisti- the work, and have given their approval for this cal analysis that impact study outcomes in AD version to be published. clinical research has been identified as a chal- lenge for healthcare providers [22], though in Author Contributions. Marjolein de Bruin- this instance, there is evidence that these may Weller contributed to the conception of the favor dupilumab [23]. The lack of longer-term work, the design of the work and the interpre- follow-up in our analysis also represents a lim- tation of the data. Esther Serra-Baldrich, Sebas- itation. This was a function of the period of tien Barbarot, Susanne Grond, and Christopher PBO-controlled observation within the trials Schuster contributed to the interpretation of themselves; comparisons can only be made the data for the work. Afaf Raibouaa contributed where there are PBO data available to populate to the conception of the work, the design of the the models. This could be resolved by the con- work, and the acquisition of data for the work. duct of full H2H trials with a longer follow-up Helmut Petto contributed to the conception of period, but such analysis lies outside the scope the work, design of the work, and the analysis of this work. We did not assess differences in and interpretation of data. Jean Phillipe Capron safety outcomes between the competing contributed to the analysis and interpretation treatments. of data. All authors contributed to critical revi- sion of the work for important intellectual content. CONCLUSIONS Disclosures. Marjolein de Bruin-Weller has Baricitinib represents an approved oral treat- served as a consultant, advisory board member, ment option for adult patients with moderate- and/or speaker for AbbVie, Almirall, Arena, to-severe AD that potentially offers more rapid Aslan, Galderma, Janssen, Leo Pharma, Pfizer, Dermatol Ther (Heidelb) (2022) 12:1481–1491 1489 Regeneron, and Sanofi-Genzyme, and Eli Lilly NonCommercial 4.0 International License, and Company. Esther Serra-Baldrich has which permits any non-commercial use, shar- received payment or honoraria for lectures, ing, adaptation, distribution and reproduction presentations, speakers’ bureaus, manuscript in any medium or format, as long as you give writing or educational events from Abbvie, appropriate credit to the original author(s) and Novartis, Almirall, Leo, Sanofi, Pfizer, and Eli the source, provide a link to the Creative Lilly and Company. Sebastien Barbarot has: Commons licence, and indicate if changes were received payment or honoraria for lectures, made. The images or other third party material presentations, speakers’ bureaus, manuscript in this article are included in the article’s writing or educational events from Almirall, Creative Commons licence, unless indicated Sanofi-Genzyme, Abbvie, Novartis, Janssen, otherwise in a credit line to the material. If Leo-Pharma, Pfizer, UCB Pharma, and Eli Lilly material is not included in the article’s Creative and Company; received support for attending Commons licence and your intended use is not meetings and/or travel from Almirall, Sanofi- permitted by statutory regulation or exceeds the Genzyme, Abbvie, Novartis, Janssen, Leo- permitted use, you will need to obtain permis- Pharma, Pfizer, UCB Pharma, and Eli Lilly and sion directly from the copyright holder. To view Company; and participated on a Data Safety a copy of this licence, visit http:// Monitoring Board or Advisory Board for Almi- creativecommons.org/licenses/by-nc/4.0/. rall, Sanofi-Genzyme, Abbvie, Novartis, Janssen, Leo-Pharma, Pfizer, UCB Pharma, and Eli Lilly and Company. Susanne Grond, Helmut Petto, and Jean Phillipe Capron are employees and REFERENCES shareholders of Eli Lilly and Company. Christopher Schuster and Afaf Raibouaa are 1. European Medicines Agency. EMA/505843/2020: employees of Eli Lilly and Company. Thomas An overview of Olumiant and why it is authorised in the EU. Amsterdam: European Medicines Werfel has: received payment or honoraria for Agency; 2017, 23 November 2017. lectures, presentations, speakers’ bureaus, manuscript writing or educational events from 2. Simpson EL, Lacour JP, Spelman L, Galimberti R, Sanofi-Regeneron, Abbvie, Pfizer, Galderma, Eichenfield LF, Bissonnette R, et al. 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