J AM ACAD DERMATOL Research Letters 1405 VOLUME 81, NUMBER 6 Correspondence to: Roni P. Dodiuk-Gad, MD, Di- The CLEAR study (NCT02074982) was a phase 3b, vision of Dermatology, Sunnybrook Health Sci- head-to-head, randomized, double-blind study on ences Centre, 2075 Bayview Ave, Room M1-700, the efficacy and safety of secukinumab compared Toronto, ON, M4N 3M5, Canada with ustekinumab over 52 weeks of treatment in adult patients with moderate-to-severe psoriasis. E-mail: rdodiukgad@gmail.com Results from the 16-week and 52-week time points Reprint requests: Neil H. Shear, MD, Division of showed higher and sustained superior efficacy of Dermatology, Sunnybrook Health Sciences secukinumab versus ustekinumab; secukinumab Centre, 2075 Bayview Ave, Room M1-737, Tor- use also provided a greater improvement in onto, ON, M4N 3M5, Canada. patient-reported outcomes (PROs), and its safety profile was comparable with ustekinumab.4,5 E-mail: neil.shear@sunnybrook.ca Patients from the secukinumab arm who completed REFERENCES 52 weeks of treatment and consented to continue 1. Olteanu C, Shear NH, Chew HF, et al. Severe physical in the open-label extension phase received complications among survivors of StevenseJohnson secukinumab 300 mg at week 52, followed by dosing syndrome and toxic epidermal necrolysis. Drug Saf. 2018; every 4 weeks to week 100. Methods for the CLEAR 41(3):277-284. study have been described in detail elsewhere.4,5 2. Dodiuk-Gad RP, Olteanu C, Feinstein A, et al. Major psycho- logical complications and decreased health-related quality of Here, we present the efficacy, safety, and PROs from life among survivors of Stevens-Johnson syndrome and toxic a total of 2 years of secukinumab treatment. epidermal necrolysis. Br J Dermatol. 2016;175(2):422-424. Of 337 patients randomized to receive secukinu- 3. Pan RY, Dao RL, Hung SI, Chung WH. Pharmacogenomic mab 300 mg, 312 completed the 52-week study, and advances in the prediction and prevention of cutaneous 303 patients entered the extension phase. In total, idiosyncratic drug reactions. Clin Pharmacol Ther. 2017;102:86-97. 4. Chen P, Lin JJ, Lu CS, et al. Carbamazepine-induced toxic 277 patients completed the 2-year extension study. effects and HLA-B*1502 screening in Taiwan. N Engl J Med. Irrespective of the analysis (observed, multiple 2011;364(12):1126-1133. imputation, modified nonresponder imputation), 5. Ko TM, Tsai CY, Chen SY, et al. Use of HLA-B*58:01 genotyping Psoriasis Area and Severity Index 75, 90, and 100, to prevent allopurinol induced severe cutaneous adverse and Investigator’s Global Assessment 2011 modified reactions in Taiwan: national prospective cohort study. BMJ. 2015;351:h4848. version 0/1 response rates with secukinumab treat- ment at week 16 were sustained up to year 2 https://doi.org/10.1016/j.jaad.2019.04.040 (Table I). A similar trend was seen for the Dermatology Life Quality Index 0/1 response. Further, the mean scores for patient assessment of psoriasis-related pain, itching, and scaling severity Secukinumab demonstrates remained low up to year 2 of secukinumab treatment sustained efficacy in clearing skin (Table I). Secukinumab treatment resulted in a mean and improving patient-reported percentage of change of 85.6% for pain, 77.6% for outcomes in patients with moderate- itching, and 81.9% for scaling from baseline to year to-severe psoriasis through 2 years 2. Furthermore, a high proportion of patients of treatment: Results from the achieved complete relief (score 0) of psoriasis- CLEAR study related pain, itching, and scaling at week 16, and To the Editor: Secukinumab is a fully human mono- the response was sustained up to year 2 (Table I). clonal antibody that selectively neutralizes interleukin Among adverse events of interest, Candida 17A, a key cytokine involved in the development of infections were reported in 24 (7.2%) patients (all psoriasis.1 Secukinumab has shown long-lasting effi- events were nonserious and did not lead to study cacy and safety in the complete spectrum of psoriatic discontinuation) and malignant or unspecified disease, including disease localized to nails, scalp, tumors were reported in 5 (1.5%) patients. palms and soles, and joints (peripheral and axial Neutropenia was reported in 1 patient during the arthritis).1-3 Given the chronic and relapsing nature of first year of treatment (mild severity, not associated psoriasis, long-term data might help to fully charac- with any infection or opportunistic infections). terize the efficacy and safety profile of secukinumab Overall, there was no increase in the rate of adverse as well as its impact on quality of life. events, and no new or unexpected signals were identified (Table II). ª 2019 by the American Academy of Dermatology, Inc. Published by In conclusion, the 2-year results from the CLEAR Elsevier Inc. This is an open access article under the CC BY-NC-ND study confirm the sustained efficacy and improved license (http://creativecommons.org/licenses/by-nc-nd/4.0/). PROs provided by secukinumab in patients with 1406 Research Letters Table I. Efficacy and patient-reported outcomes through year 2 of secukinumab 300-mg treatment Week 16 Year 1 Year 2 Efficacy As observed MI mNRI As observed MI mNRI As observed MI mNRI PASI 75 94.5 (310/328) 94.2 (315/334) 93.1 (311/334) 93.7 (282/301) 92.4 (308/334) 91.6 (306/334) 89.6 (138/154) 83.1 (278/334) 83.8 (280/334) PASI 90 80.5 (264/328) 80.1 (268/334) 79.0 (264/334) 78.4 (236/301) 76.3 (255/334) 74.9 (250/334) 74.7 (115/154) 62.6 (209/334) 66.8 (223/334) PASI 100 45.1 (148/328) 45.0 (150/334) 44.3 (148/334) 48.2 (145/301) 45.8 (153/334) 44.9 (150/334) 47.4 (73/154) 36.9 (123/334) 38.6 (129/334) IGA mod 2011 0/1 84.5 (277/328) 84.3 (282/334) 83.2 (278/334) 81.7 (246/301) 80.2 (268/334) 78.1 (261/334) 68.8 (106/154) 66.5 (222/334) 66.5 (222/334) Week 16 Year 1 Year 2 PROs As observed LOCF As observed LOCF As observed LOCF DLQI 0/1 72.2 (236/327) 71.9 (238/331) 71.9 (210/292) 71.6 (237/331) 66.0 (105/159) 65.9 (218/331) Pain, mean score (m) 0.8 (327) 0.8 (333) 0.8 (292) 0.8 (333) 0.7 (159) 0.9 (333) Itching, mean score (m) 1.2 (327) 1.2 (333) 1.2 (292) 1.3 (333) 1.3 (159) 1.5 (333) Scaling, mean score (m) 0.8 (327) 0.8 (333) 1.0 (292) 1.0 (333) 1.1 (159) 1.3 (333) As observed Complete relief* Week 16 Year 1 Year 2 Pain 69.4 (177/255) 67.1 (151/225) 70.9 (90/127) Itching 49.7 (157/316) 48.9 (138/282) 47.4 (72/152) Scaling 61.2 (197/322) 53.3 (153/287) 54.8 (86/157) Values are % (n/m), except where indicated. Efficacy variables and PROs were primarily assessed by using observed values (no imputation of missing values). In addition, the MI and mNRI methods were used as sensitivity analyses for efficacy variables, and the LOCF method was used for PROs. Missing values were imputed in MI analysis by using the missing at random assumption. In mNRI analyses, the missing values were imputed as nonresponse regardless of the reason for missing data, except if the patient had been a responder for 2 consecutive visits before the study completion or discontinuation or if the patient had been a responder at visits both before and after the missed visit. In LOCF analyses, the last available measurement for each patient was carried forward to all later visits. DLQI, Dermatology Life Quality Index; IGA mod 2011, Investigator Global Assessment 2011 modified version; LOCF, last observation carried forward; m, number of patients evaluable; MI, multiple imputation; mNRI, modified nonresponder imputation; n, number of patients with response; PASI, Psoriasis Area Severity Index; PROs, patient-reported outcomes. *Complete relief of psoriasis-related pain, itching, and scaling was defined as absence of symptoms (item score of 0) in patients with baseline score for symptom [0. J AM ACAD DERMATOL DECEMBER 2019 J AM ACAD DERMATOL Research Letters 1407 VOLUME 81, NUMBER 6 Table II. Adverse events during 2-year study period Secukinumab 300 mg Overall, Up to year 1, From [1 year to end Adverse event N = 335, n (%) N = 335, n (%) of study, N = 307, n (%) Any adverse event 299 (89.3) 286 (85.4) 198 (64.5) Serious adverse event 41 (12.2) 32 (9.6) 13 (4.2) Death 0 (0) 0 (0) 0 (0) Adverse events leading to study treatment discontinuation 18 (5.4) 11 (3.3) 8 (2.6) Primary system organ class Infections and infestations 231 (69.0) 197 (58.8) 137 (44.6) Most common ($5%)* Nasopharyngitis 96 (28.7) 77 (23.0) 39 (12.7) Headache 50 (14.9) 40 (11.9) 18 (5.9) Upper respiratory tract infection 42 (12.5) 31 (9.3) 23 (7.5) Arthralgia 36 (10.7) 26 (7.8) 13 (4.2) Influenza 33 (9.9) 22 (6.6) 12 (3.9) Oropharyngeal pain 32 (9.6) 28 (8.4) 4 (1.3) Back pain 29 (8.7) 21 (6.3) 11 (3.6) Pruritus 25 (7.5) 20 (6.0) 6 (2.0) Diarrhea 23 (6.9) 23 (6.9) 4 (1.3) Psoriasis 22 (6.6) 12 (3.6) 11 (3.6) Cough 21 (6.3) 13 (3.9) 10 (3.3) Bronchitis 20 (6.0) 13 (3.9) 9 (2.9) Fatigue 20 (6.0) 18 (5.4) 2 (0.7) Eczema 19 (5.7) 15 (4.5) 5 (1.6) Conjunctivitis 18 (5.4) 16 (4.8) 4 (1.3) Select adverse events of interest Candida infectionsy 24 (7.2) 19 (5.7) 8 (2.6) Oral candidiasis 15 (4.5) 12 (3.6) 5 (1.6) Vulvovaginal candidiasis 4 (1.2) 3 (0.9) 1 (0.3) Genital candidiasis 2 (0.6) 1 (0.3) 1 (0.3) Esophageal candidiasis 2 (0.6) 2 (0.6) 0 (0) Balanitis candida 1 (0.3) 0 (0) 1 (0.3) Candida infection 1 (0.3) 1 (0.3) 0 (0) Oropharyngeal candidiasis 1 (0.3) 1 (0.3) 0 (0) Skin candida 1 (0.3) 1 (0.3) 0 (0) Malignant or unspecified tumorsz 5 (1.5) 4 (1.2) 1 (0.3) Malignant melanoma in situ 2 (0.6) 2 (0.6) 0 (0) Basal cell carcinoma 1 (0.3) 0 (0) 1 (0.3) Keratoacanthoma 1 (0.3) 1 (0.3) 0 (0) Lung adenocarcinoma 1 (0.3) 1 (0.3) 0 (0) Events listed under Candida infections and Malignant or unspecified tumors are preferred terms. One year is defined as 365 days. *Preferred term. y High-level term. z Standard MedDRA query. moderate-to-severe plaque psoriasis, while main- Stephen Tyring, MD, PhD,e K€ulli Kingo, MD, taining a favorable safety profile. PhD,f Michael Ziv, MD, BSc,g Andreas Pinter, MD,h Ronald Vender, MD, FRCPC,i,j Aude The authors thank Dhaval Gupta, MPH (Novartis Lacombe, PharmD,k Summer Xia, MSc,l Healthcare Pvt Ltd, India), and Jackie L. Johnson, PhD Vaishali Bhosekar, MSc,m Isabelle Gilloteau, (Novartis Ireland Ltd), for providing medical writing MSc, MPH,k Adriana Guana, MD,n and support, which was funded by Novartis Pharma AG, Andrew Blauvelt, MD, MBAo Basel, Switzerland, in accordance with Good Publication Practice guidelines (http://www.ismpp.org/gpp3). From the Research Institute and Comprehensive a Diamant Thaçi, MD, Lluıs Puig, MD, PhD, b Center for Inflammation Medicine, University of Kristian Reich, MD,c Tsen-Fang Tsai, MD,d Luebeck, Luebeck, Germanya; Department of 1408 Research Letters J AM ACAD DERMATOL DECEMBER 2019 Dermatology, Hospital de la Santa Creu i Sant research site has received patient fees, and Prof Pau, Universitat Aut onoma de Barcelona, Bar- Reich has received fees if acting as coordinating celona, Spainb; Dermatologikum Berlin and investigator. Dr Tsai has served as an investi- SCIderm Research Institute, Hamburg, Germa- gator or advisor and speaker and has received nyc; Department of Dermatology, National fees and honoraria from Janssen-Cilag, AbbVie, Taiwan University Hospital, National Taiwan Pfizer, Leo Pharmaceuticals, Novartis, Celgene, University College of Medicine, Taipei, Taiwand; Galderma, Eli-Lilly, Boehringer Ingelheim, GSK, University of Texas Health Science Center and MSD, Allegra, and Tanabe. Dr Tsai’s institute Center for Clinical Studies, Houston, Texase; has received fees for his role as an investigator. Dermatology Clinic, Tartu University Hospital, Dr Tyring has served as a principal investigator Department of Dermatology, University of Tartu, and his institution has received grant and Tartu, Estoniaf; Emek Medical Center, Afula, research funding from Novartis. Dr Kingo has Israelg; Department of Dermatology, University received fees for serving as an investigator in of Frankfurt, Frankfurt am Main, Germanyh; studies sponsored by Celgene, Merck, Mitsubishi Dermatrials Research Inc, Hamilton, Canadai; Tanabe Pharma, Novartis, Regeneron Pharma- Venderm Innovations in Psoriasis, Hamilton, ceuticals, and Sandoz. Dr Ziv has served as Canadaj; Novartis Pharma AG, Basel, Switzer- principal investigator and has received fees from landk; Novartis Beijing Novartis Pharma Co Ltd, Novartis. Dr Pinter has served as a scientific Shanghai, Chinal; Novartis Healthcare Pvt Ltd, advisor or clinical study investigator for AbbVie, Hyderabad, Indiam; Novartis Pharmaceuticals Allmirall-Hermal, Amgen, Biogen Idec, Corporation, East Hanover, New Jerseyn; and Boehringer-Ingelheim, Celgene, GSK, Eli-Lilly, Oregon Medical Research Center, Portland, Galderma, Hexal, Janssen, Leo Pharma, Medac, Oregono Merck Serono, Mitsubishi, MSD, Novartis, Pfizer, Tigercat Pharma, Regeneron, Roche, Sandoz Funding sources: Supported by Novartis Pharma Biopharmaceuticals, Schering-Plough, and UCB AG, Basel, Switzerland. pharma. Dr Pinter has served as a paid speaker Conflicts of interest: Dr Thaci has served as a for AbbVie, Celgene, Eli-Lilly, Janssen, Leo consultant, advisor, and speaker and has Pharma, Medac, Novartis, and Sanofi Genzyme. received honoraria from AbbVie, Almirall, Am- Dr Vender has served as an advisory board gen, Boehringer Ingelheim, Celgene, Dignity, Dr member, investigator, and on the speakers bu- Reddy, Galapagos, GSK, Janssen, Leo, Lilly, reau and has received honoraria from Novartis, Morphosis, MSD, Novartis, Pfizer, Regeneron, AbbVie, Janssen, Lilly, UCB, Amgen, Celgene, Sanofi, and UCB. Dr Thaci’s institute has Pfizer, and Bauch Health. Ms Lacombe, Ms Xia, received research grants from Celgene and and Ms Gilloteau are employees of Novartis. Dr Novartis. Dr Puig has served as a consultant Guana and Ms Bhosekar were employees of and speaker and has received fees and honorar- Novartis during the conduct of the study and ia from AbbVie, Almirall, Amgen, Baxalta, development of the manuscript. Dr Blauvelt has Biogen, Boehringer Ingelheim, Celgene, Gebro, served as a scientific adviser or clinical study Janssen, Leo-Pharma, Lilly, Merck-Serono, MSD, investigator for AbbVie, Aclaris, Akros, Allergan, Novartis, Pfizer, Regeneron, Roche, and Sandoz. Almirall, Amgen, Boehringer Ingelheim, Cel- Dr Puig’s institution has received research fund- gene, Dermavant, Dermira Inc, Eli Lilly and ing in relationship with the treatment of psoriasis Company, Galderma, Genentech/Roche, GlaxoS- from AbbVie, Amgen, Janssen, Lilly, Novartis, mithKline, Janssen, Leo, Meiji, Merck Sharp & and Pfizer. Dr Reich has served as advisor or Dohme, Novartis, Pfizer, Purdue Pharma, Re- paid speaker and participated in clinical trials generon, Revance, Sandoz, Sanofi Genzyme, sponsored by AbbVie, Affibody, Almirall, Amgen, Sienna Pharmaceuticals, Sun Pharma, UCB Biogen Idec, Boehringer Ingelheim, Celgene, Pharma, Valeant, and Vidac and as a paid Covagen, Forward Pharma, Fresenius Medical speaker for Eli Lilly and Company, Janssen, Care, GlaxoSmithKline, Janssen-Cilag, Kyowa Regeneron, and Sanofi Genzyme. Kirin, Leo, Lilly, Medac, Merck Sharp & Dohme Previously presented a synopsis of the current Corp, Miltenyi, Novartis, Ocean Pharma, Pfizer, research as an ePoster at the 26th European Samsung Bioepis, Sanofi, Takeda, UCB Pharma, Academy of Dermatology and Venereology Valeant, and Xenoport. Dr Reich has received Congress, in Geneva, Switzerland, on September honoraria for his role as advisor and speaker. 13e17, 2017. For participating in clinical trials, Dr Reich’s J AM ACAD DERMATOL Research Letters 1409 VOLUME 81, NUMBER 6 Reprints not available from the authors. Correspondence to: Diamant Thaçi, MD, Research Institute and Comprehensive Center for Inflam- mation Medicine, University of Luebeck, Ratze- burger Allee 160, 23538 Luebeck, Germany E-mail: diamant.thaci@uksh.de and diamant. thaci@uni-luebeck.de REFERENCES 1. Armstrong AW, Vender R, Kircik L. Secukinumab in the treatment of palmoplantar, nail, scalp, and pustular psoriasis. J Clin Aesthet Dermatol. 2016;9(6):S12-S16. 2. Mease PJ, McInnes IB, Kirkham B, et al. Secukinumab inhibition of interleukin-17A in patients with psoriatic arthritis. N Engl J Med. 2015;373:1329-1339. 3. Baeten D, Sieper J, Braun J, et al. Secukinumab, an interleukin-17A inhibitor, in ankylosing spondylitis. N Engl J Med. 2015;373:2534-2548. 4. Thaci D, Blauvelt A, Reich K, et al. Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate to severe plaque psoriasis: CLEAR, a randomized controlled trial. J Am Acad Dermatol. 2015;73:400-409. 5. Blauvelt A, Reich K, Tsai TF, et al. Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate-to-severe plaque psoriasis up to 1 year: results from the CLEAR study. J Am Acad Dermatol. 2017;76(1): 60-69.e9. https://doi.org/10.1016/j.jaad.2019.04.045 Association of particulate matter air pollution and itch: A digital epidemiology approach To the Editor: Ambient air pollution secondary to industrialization is a growing health concern with the potential to cause exposure-related skin toxicity.1 Among skin conditions, itch may be especially sus- ceptible to environmental modulation, given that free nerve endings of sensory neurons are located in the epidermis.2 Although several air pollutants are postulated to affect health, one well-studied marker of air quality is atmospheric particulate matter no Fig 1. Air pollution and Google search volume index larger than 2.5 m (PM2.5). Fine particulate matter of (SVI) for 49 States in the United States in 2014. PM2.5. this size has important health effects, given its ability Particulate matter no larger than 2.5 m. to penetrate the body systemically and serve as a carrier of pathogens and toxins.1 We thus hypothesized that increasing levels of PM2.5 are evaluated within the United States in 2014 for the associated with increased population-level search term itch, and for purposes of comparison, SVI data interest in itch as a proxy for itch sensation. for the term acne were evaluated. We obtained data Google Trends is an open-access database on annual state averages for PM2.5 for 2014 from the aggregating search queries across various regions US Centers for Disease Control and Prevention’s that has been used for health care research, with National Environmental Public Health Tracking successful validation against external data sets.3 Network. Multivariate linear regression was Search volume index (SVI) is a normalized value conducted to examine the association between SVI ranging from 0 to 100 that indicates the quantity of for skin-related complaints and PM2.5 adjusted for queries for a searched topic relative to all other climate, population density, and percentage of queries within the given time frame. SVI data were population located in urban areas.